Soluble starch-derived porous carbon microspheres with interconnected and hierarchical structure by a low dosage KOH activation for ultrahigh rate supercapacitors.

The developed porous structure and high density are essential to enhance the bulk performance of carbon-based supercapacitors. Nevertheless, it remains a significant challenge to optimize the balance between the porous structure and the density of carbon materials to realize superior gravimetric and areal electrochemical performance. The soluble starch-derived interconnected hierarchical porous carbon microspheres were prepared through a simple hydrothermal treatment succeeded by chemical activation with a low dosage of KOH. Due to the formation of interconnected spherical morphology, hierarchical porous structure, reasonable mesopore volume (0.33 cm3 g-1) and specific surface area (1162 m2 g-1), the prepared carbon microsphere has an ultrahigh capacitance of 394 F g-1 @ 1 A g-1 and a high capacitance retention of 62.7 % @ 80 A g-1. The assembled two-electrode device displays good cycle stability after 20,000 cycles and an ultra-high energy density of 11.6 Wh kg-1 @ 250 W kg-1. Moreover, the sample still exhibits a specific capacitance of 165 F g-1 @ 1 A g-1 at a high mass loading of 10 mg cm-2, resulting in a high areal capacitance of 1.65 F cm-2. The strategy proposed in this study, via a low-dose KOH activation process, provides the way for the synthesis of high-performance porous carbon materials.

CD95 promotes stemness of colorectal cancer cells by lncRNA MALAT1.

Colorectal cancer (CRC) is the second most fatal cancer. Many studies have shown that cancer stemness contributes to resistance to conventional chemotherapy and poor prognosis. However, the mechanisms involved in maintaining cancer stemness in CRC are still obscure and few clinical drugs were used to target cancer stemness. Previous studies had reported CD95 increases the stemness of cancer cells with long-term stimulation of exogenous agonist CD95 ligand (CD95L). However, the expression of CD95L is relative low in certain human tumor tissues. In this study, we found that CD95 was highly expressed in CRC cells, and in vitro it promoted the tumorsphere formation, chemotherapy resistance and in vivo tumor growth without stimulation of exogenous CD95L. Mechanistically, the bulk and single-cell RNA-sequencing results suggested that CD95 promotes stemness of CRC cells through upregulation of long non-coding RNAs metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1). MALAT1 knockdown inhibited CD95-induced tumorsphere formation and chemotherapy resistance. In summary, our findings reveal that CD95 has the capability to modulate cancer stemness via the action of the lncRNA MALAT1. Targeting CD95 may be a promising strategy to inhibit cancer stemness in CRC.

Constructing Interconnected Microporous Structures in Carbon by Homogeneous Activation as a Sustainable Electrode Material for High-Performance Supercapacitors.

Microporous carbon attracts attention as an electrode material for supercapacitors. However, a large number of deep and distorted mesoporous and macroporous structures are usually created by non-uniform etching, resulting in underutilized internal space. Homogeneous activation has been considered by researchers as a necessary condition for the formation of interconnected microporous structures in carbon materials. Herein, a simple strategy of hydrothermal introduction of defects followed by homogeneous activation for the preparation of microporous carbon was developed for the synthesis of electrode materials for high-performance supercapacitors. The optimized sample with defect-enriched microporous structure and large specific surface area has a specific capacity of 315 F g-1 (1 A g-1) in KOH solution, and the assembled symmetric supercapacitor achieves a high energy density of 7.3 Wh kg-1 at a power density of 250 W kg-1. This work is interesting because it not only demonstrates that rational design of electrode materials is important to boost the performance of supercapacitors, but also provides inspiration for the design of efficient supercapacitors in the future.

The role of lipid metabolism in tumor immune microenvironment and potential therapeutic strategies.

Aberrant lipid metabolism is nonnegligible for tumor cells to adapt to the tumor microenvironment (TME). It plays a significant role in the amount and function of immune cells, including tumor-associated macrophages, T cells, dendritic cells and marrow-derived suppressor cells. It is well-known that the immune response in TME is suppressed and lipid metabolism is closely involved in this process. Immunotherapy, containing anti-PD1/PDL1 therapy and adoptive T cell therapy, is a crucial clinical cancer therapeutic strategy nowadays, but they display a low-sensibility in certain cancers. In this review, we mainly discussed the importance of lipid metabolism in the formation of immunosuppressive TME, and explored the effectiveness and sensitivity of immunotherapy treatment by regulating the lipid metabolism.

Toxicity mechanisms regulating bone differentiation and development defects following abnormal expressions of miR-30c targeted by triclosan in zebrafish.

As a ubiquitous environmental estrogen-disrupting chemical, triclosan (TCS) can induce severe osteotoxicity; however, the underlying molecular mechanisms remain uncertain. Herein, we evaluated the toxic effects of TCS on the development of cartilage and osteogenesis in 5-dpf zebrafish. Under TCS exposure from 62.5 to 250 µg/L, several osteodevelopmental malformations were observed, such as defect of craniofacial cartilage, pharyngeal arch cartilage dysplasia, and impairments on skeletal mineralization. Further, the morphology of mature chondrocytes became swollen and deformed, their number decreased, nucleus displacement occurred, and most immature chondrocytes were crowded at both ends of ceratobranchial. SEM observation of larval caudal fin revealed that, the layer of collagen fibers and the mineralized calcium nodules were significantly decreased, with the collagen fibers becoming shorter upon TCS exposure. The activity of bone-derived alkaline phosphatase significantly reduced, and marker functional genes related to cartilage and osteoblast development were abnormally expressed. RNA-seq and bioinformatics analysis indicated, that changes in marker genes intimately related to the negative regulation of miR-30c-5p overexpression targeted by TCS, and the up-regulation of miR-30c induced bone developmental defects by inhibiting the bone morphogenetic protein (BMP) signaling pathway. These findings were confirmed by artificially intervening the expression of miR-30c and using BMP pathway agonists in vivo. In sum, TCS induced osteototoxicity by targeting miR-30c up-regulation and interfering in the BMP signaling pathway. These findings enhance mechanistic understanding of TCS-induced spontaneous bone disorders and bone metastatic diseases. Further research is necessary to monitor chronic TCS-exposure levels in surrounding environments and develop relevant safety precautions based on TCS environmental risk.

Triclosan regulates alternative splicing events of nerve-related genes through RNA-binding protein CELF2 to induce zebrafish neurotoxicity.

Herein, we demonstrated that triclosan (TCS) induced neurotoxicity mediated by pre-mRNA alternative splicing (AS). TCS exposure resulted in a series of phenotypic malformations, abnormal locomotor behavior, circadian rhythm disorder and inhibited AChE activity. High throughput mRNA sequencing revealed that TCS regulated the AS events of nerve-related genes. Meanwhile, abnormal expression was observed in marker genes related to nerve cell migration, axon guidance and myelination. The expression of mitochondrial apoptosis activator bcl2l11 was significantly increased under TCS exposure. Interestingly, CELF2 as one of the important RNA-binding proteins was closely related to the AS events, and its mRNA and protein expression levels were significantly increased in zebrafish brain under acute or chronic TCS exposure. Functional knock-down and over-expression of celf2 confirmed that TCS led to nervous system injury and developmental defects through the CELF2-mediated AS events of genes (mbpa, mef2d, u2af2b and matn3b). Histopathological injury, phenotypic malformation, abnormal locomotor behavior and changes in neuromarkers all confirmed the biological functions of CELF2 in zebrafish brain. These findings demonstrate that TCS might regulate some of the AS events of nerve-related genes through upregulating the expression of CELF2. Thus, CELF2 may serve as a target for the prevention, diagnosis and treatment of contaminant-induced neurological diseases.

Risk assessment of cardiotoxicity to zebrafish (Danio rerio) by environmental exposure to triclosan and its derivatives.

Triclosan (TCS) and its two derivatives (2,4-dichlorophenol and 2,4,6-trichlorophenol) are priority pollutants that coexist in aquatic environments. Joint exposure of TCS, 2,4-dichlorophenol and 2,4,6-trichlorophenol, hereafter referred to as TCS-DT, contributes severe toxicity to aquatic organisms. There is currently a paucity of data regarding TCS-DT molecular toxicity, especially on cardiac diseases. We used zebrafish (Danio rerio) as a model organism, and evaluated the molecular-level cardiotoxicity induced by TCS-DT from embryonic to adult stages. TCS-DT exposure prominently led to phenotypic malformations, such as pericardial cysts, cardiac bleeding, increased SV-BA distance, decreased heart rate and reduced ejection fraction, as well as abnormal swimming behavior. Analyses of the GO and KEGG pathways revealed enrichment pathways related to cardiac development and screened for significantly down-regulated adrenaline signaling in cardiomyocytes. The cardiac marker genes (amhc, cmlc2, vmhc, and nkx2.5) were obtained through protein-protein interaction (PPI) networks, and expressed as down-regulation by WISH. After chronic exposure to TCS-DT from 30 to 90-dpf, both body mass and heart indexes prominently increased, showing myocardial hypertrophy, abnormal heart rate and histopathological injury. Heart tissue damage included disordered and ruptured myocardial fibers, broken and dissolved myofilaments, nuclear pyknosis, mitochondrial injury and inflammatory cell infiltration. Further, abnormal changes in a series of cardiac functions-related biomarkers, including superoxide dismutase, triglyceride, lactate dehydrogenase and creatinine kinase MB, provided evidence for cardiac pathological responses. These results highlight the molecular mechanisms involving TCS-DT induced cardiac toxicity, and provide theoretical data to guide prevention and treatment of pollutant-induced cardiac diseases.

Differential mechanisms regarding triclosan vs. bisphenol A and fluorene-9-bisphenol induced zebrafish lipid-metabolism disorders by RNA-Seq.

Exposure of endocrine disrupting chemicals (EDCs) is closely related to induction of obesity, nonalcoholic fatty liver disease (NAFLD) and other lipid-metabolism diseases. Herein, we compared the effects of three EDCs exposure (triclosan, bisphenol A and fluorene-9-bisphenol) on lipid metabolism in zebrfish (Danio rerio). The differential lipid-metabolism disorders were analyzed in depth through RNA-Seq and qRT-PCR, as well as assessment of the relationship between lipid disorder and RNA methylation. Histopathological observation along with varying physiological and biochemical indexes all identified that triclosan and bisphenol A induced liver fat accumulation in acute and chronic exposure. RNA-Seq analysis showed that triclosan exposure disrupted multiple physiological processes including drug metabolism, sucrose metabolism, fat metabolism and bile secretion. The dysregulation of lipid-metabolism related genes indicated that liver steatosis in triclosan and BPA-exposed zebrafish resulted from increased fatty acid synthetase, and uptake and suppression of ß-oxidation. Besides, the dysregulation of pro-inflammatory genes and endoplasmic reticulum stress showed that triclosan and bisphenol A exposure not only induced occurrence of NAFLD, but also promoted progression of hepatic inflammation. However, no significant effect on lipid metabolism was observed in fluorene-9-bisphenol-exposed treatment although the larval phenotypic malformation was found compared to the control group. Moreover, EDCs exposure led to decreased global m6A level and abnormal expression of m6A modulators in larvae. Especially, the expression of demethylase FTO (fat mass and obesity-associated protein) was significantly increased in triclosan-exposure treatment. These findings are conductive for us to deeply understand the underlying molecular mechanisms regarding the obesity and NAFLD from EDCs exposure.

Triclosan induces zebrafish neurotoxicity by abnormal expression of miR-219 targeting oligodendrocyte differentiation of central nervous system.

Triclosan (TCS) is ubiquitous in a wide range of personal care and consumer products, and it is acute/chronic exposure may result in several nervous system disorders. Previous studies demonstrated TCS-induced abnormal expression of miRNAs, but no investigations focused on upstream changes of miRNAs and associated molecular mechanisms. Herein, phenotype observation and behavioral analysis confirmed that TCS exposure (0, 62.5, 125, 250 µg/L) led to developmental neurotoxicity in zebrafish larvae, especially for oligodendrocyte precursor cells (OPCs). High-throughput sequencing demonstrated the critical role of miR-219 in the differentiation of OPCs. Larvae with miR-219 depletion showed the same phenotype caused by TCS. Functional tests with miR-219 knock-down and over-expression showed that miR-219 promoted differentiation of OPCs by acting on myelination inhibitors. The miR-219 also protected against TCS-induced inhibition of cell differentiation. Several epigenetic features were identified to reveal potential upstream regulatory mechanisms of miR-219. In particular, five CpG islands hyper-methylated with increasing TCS concentrations in the promoter region of miR-219. TCS inhibited OPC differentiation by influencing epigenetic effects on miR-219-related pathways, contributing to severe neurotoxicity. These findings enhance our understanding of epigenetic mechanisms affecting demyelination diseases due to TCS exposure, and also provide theoretical guidance for early intervention and gene therapy of environmentally induced diseases.

Comprehensive utilization of edible mushroom Auricularia auricula waste residue-Extraction, physicochemical properties of melanin and its antioxidant activity.

In order to promote the comprehensive utilization of the Auricularia auricula waste residue, the extraction process and the physicochemical properties of melanin from A. auricula waste residue were studied. Furthermore, the chemical antioxidant activity of waste residue melanin and its protective effect on cell oxidative injury induced by H2O2 were investigated. The results indicated that the ultrasonic-assisted extraction process could be used to extract the melanin from A. auricula waste residue. Melanin had a good solubility in alkali solution and exhibited a certain stability to thermal. There was no significant difference between A. auricula melanin control group and waste residue melanin on ABTS, DPPH, and hydroxyl radical scavenging activity. Waste residue melanin significantly inhibited the cell death caused by H2O2, and the cell viability was restored to 98.09 ± 5.97% when the melanin concentration was 1.6 mg/ml. Cell morphology observation confirmed that the melanin ameliorated the morphological changes of cells induced by oxidative stress.

Effects of miR-181a-5p abnormal expression on zebrafish (Danio rerio) vascular development following triclosan exposure.

Triclosan (TCS), one of the important bactericides, is widely used in personal care products, and its chronic exposure leads to severe toxic effects on the growth and development of blood vessels in zebrafish (Danio rerio). Herein, we screened out three differentially expressed miRNAs (miR-181a-5p, miR-132-3p and miR-128-3p) by sequencing and qRT-PCR analyses of 4-96-hpf TCS-exposed zebrafish, among which miR-181a-5p was found to regulate many signaling pathways involved in fatty acid biosynthesis and phosphatidylimositol signaling systems. By O-dianisidine staining, TCS-exposure resulted in decreased distribution of red blood cells and induced blood hypercoagulable state and thrombotic effects. Defective subintestinal veins (SIVs), and decreased branching and curvature of blood vessels were observed with increasing TCS-exposure concentrations. After microinjection of miR-181a-5p mimic and inhibitor, zebrafish malformation type and percentage were prominently increased such as distorted SIV vessels along with reduced venation and abnormal branches by ALP staining. Overexpressed miR-181a-5p had a greater effect on development and branching patterns of arteries and veins than its knockdown. By laser confocal microscopy observation, the 72-hpf Tg (flk1: mCherry) zebrafish obviously displayed vascular proliferation and ablation in the miR-181a-5p mimic group. Microinjection of miR-181a-5p mimics and inhibitors led to abnormal expressions (20-50%) of two key target genes (pax2a and vash2) by WISH, and increased malformation percentages (18-45%) by IOD analysis. Overexpression of vash2 led to the inhibitory or promoting effects on the expression of PI3K signaling pathway-related genes, proving that the effect of vash2 on development of blood vessels could be realized by inhibiting PI3K signaling pathway. These observations lay theoretical foundation for deep insight into the molecular mechanisms on TCS-induced cardiovascular diseases.

Paeoniflorin Inhibits Migration- and Invasion-Promoting Capacities of Gastric Cancer Associated Fibroblasts.

OBJECTIVE: To investigate the inhibitory effects of paeoniflorin on migration- and invasion-promoting capacities of gastric cancer associated fibroblasts (GCAFs) and to explore the molecular mechanism underlying the effects. METHODS: Paired gastric normal fifbroblast (GNF) and GCAF cultures were established from resected tissues. GCAFs were treated with control medium, or 2.5, 5 or 10 µg/mL paeoniflorin. Conditioned media were prepared from GNFs, GCAFs, control-treated GCAFs and paeoniflorin-treated GCAFs, and used to culture AGS human gastric cancer cells. The migration and invasion capacities of AGS cells were determined with wound healing test and transwell invasion assay, respectively. The interleukin 6 (IL-6) mRNA and microRNA-149 expression in GCAFs were detected by reverse transcription-quantitative polymerase chain reaction. The IL-6 protein expression and secretion by GCAFs were measured with Western blot and enzyme-linked immunosorbent assay analysis, respectively. The protein levels of phosphorylated signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase (MMP) and MMP9 in AGS cells were examined by Western blot. RESULTS: GCAFs displayed enhanced capacities to induce AGS cell migration and invasion as compared with GNFs. Paeoniflorin treatment significantly inhibited the migration- and invasion-promoting capacities of GCAFs (P<0.05). GCAFs produced and secreted more IL-6 into the conditioned medium than GNFs, leading to over-activation of STAT3-MMP signaling in AGS cells. Paeoniflorin suppressed IL-6 production and secretion by up-regulating microRNA149 expression in GCAFs, and subsequently prevented GCAFs from activating IL-6-STAT3-MMP signaling of AGS cells. CONCLUSIONS: Paeoniflorin inhibits the migration- and invasion-promoting capacities of GCAFs by targeting microRNA-149 and IL-6. Paeoniflorin is potentially a novel therapeutic agent against cancer microenvironment.