Thermal-Responsive MXene-DNA Hydrogel for Near-Infrared Light Triggered Localized Photothermal-Chemo Synergistic Cancer Therapy.

Stimuli-responsive DNA hydrogels are promising candidates for cancer treatment, as they not only possess biocompatible and biodegradable 3D network structures as highly efficient carriers for therapeutic agents but also are capable of undergoing programmable gel-to-solution transition upon external stimuli to achieve controlled delivery. Herein, a promising platform for highly efficient photothermal-chemo synergistic cancer therapy is established by integrating DNA hydrogels with Ti3 C2 TX -based MXene as a photothermal agent and doxorubicin (DOX) as a loaded chemotherapeutic agent. Upon the irradiation of near-infrared light (NIR), temperature rise caused by photothermal MXene nanosheets triggers the reversible gel-to-solution transition of the DOX-loaded MXene-DNA hydrogel, during which the DNA duplex crosslinking structures unwind to release therapeutic agents for efficient localized cancer therapy. Removal of the NIR irradiation results in the re-formation of DNA duplex structures and the hydrogel matrix, and the recombination of free DOX and adaptive hydrogel transformations can also be achieved. As demonstrated by both in vitro and in vivo models, the MXene-DNA hydrogel system, with excellent biocompatibility and injectability, dynamically NIR-triggered drug delivery, and enhanced drug uptake under mild hyperthermia conditions, exhibits efficient localized cancer treatment with fewer side effects to the organisms.

Adipocyte-derived kynurenine promotes obesity and insulin resistance by activating the AhR/STAT3/IL-6 signaling.

Aberrant amino acid metabolism is a common event in obesity. Particularly, subjects with obesity are characterized by the excessive plasma kynurenine (Kyn). However, the primary source of Kyn and its impact on metabolic syndrome are yet to be fully addressed. Herein, we show that the overexpressed indoleamine 2,3-dioxygenase 1 (IDO1) in adipocytes predominantly contributes to the excessive Kyn, indicating a central role of adipocytes in Kyn metabolism. Depletion of Ido1 in adipocytes abrogates Kyn accumulation, protecting mice against obesity. Mechanistically, Kyn impairs lipid homeostasis in adipocytes via activating the aryl hydrocarbon receptor (AhR)/Signal transducer and activator of transcription 3 /interleukin-6 signaling. Genetic ablation of AhR in adipocytes abolishes the effect of Kyn. Moreover, supplementation of vitamin B6 ameliorated Kyn accumulation, protecting mice from obesity. Collectively, our data support that adipocytes are the primary source of increased circulating Kyn, while elimination of accumulated Kyn could be a viable strategy against obesity.

Phosphate Starvation by Energy Metabolism Disturbance in Candida albicansvip1Δ/Δ Induces Lipid Droplet Accumulation and Cell Membrane Damage.

Phosphorus in the form of phosphate (Pi) is an essential element for metabolic processes, including lipid metabolism. In yeast, the inositol polyphosphate kinase vip1 mediated synthesis of inositol heptakisphosphate (IP7) regulates the phosphate-responsive (PHO) signaling pathway, which plays an important role in response to Pi stress. The role of vip1 in Pi stress and lipid metabolism of Candida albicans has not yet been studied. We found that when vip1Δ/Δ was grown in glucose medium, if Pi was supplemented in the medium or mitochondrial Pi transporter was overexpressed in the strain, the lipid droplet (LD) content was reduced and membrane damage was alleviated. However, further studies showed that neither the addition of Pi nor the overexpression of the Pi transporter affected the energy balance of vip1Δ/Δ. In addition, the LD content of vip1Δ/Δ grown in Pi limitation medium PNMC was lower than that grown in SC, and the metabolic activity of vip1Δ/Δ grown in PNMC was also lower than that grown in SC medium. This suggests that the increase in Pi demand by a high energy metabolic rate is the cause of LD accumulation in vip1Δ/Δ. In addition, in the vip1Δ/Δ strains, the core transcription factor PHO4 in the PHO pathway was transported to the vacuole and degraded, which reduced the pathway activity. However, this does not mean that knocking out vip1 completely blocks the activation of the PHO pathway, because the LD content of vip1Δ/Δ grown in the medium with ß-glycerol phosphate as the Pi source was significantly reduced. In summary, the increased Pi demand and the decreased PHO pathway activity in vip1Δ/Δ ultimately lead to LD accumulation and cell membrane damage.

Actin Cytoskeleton-Disrupting and Magnetic Field-Responsive Multivalent Supramolecular Assemblies for Efficient Cancer Therapy.

Actin cytoskeleton disruption is a promising and intriguing anticancer strategy, but their efficiency is frequently compromised by severe side effects of the actin cytoskeleton-disrupting agents. In this study, we constructed the biocompatible actin cytoskeleton-targeting multivalent supramolecular assemblies that specifically target and disrupt the tumor actin cytoskeleton for cancer therapy. The assemblies were composed of ß-cyclodextrin-grafted hyaluronic acid (HACD) and iron oxide magnetic nanoparticles (MNPs) grafted by an actin-binding peptide (ABP) and adamantane (Ada)-modified polylysine. Owing to the multivalent binding between cyclodextrin and Ada, HACD, and peptide-grafted MNPs (MNP-ABP-Ada) could self-assemble to form MNP-ABP-Ada⊂HACD nanofibers in a geomagnetism-dependent manner. Furthermore, the presence of ABP rendered the assemblies to efficiently target the actin cytoskeleton. Interestingly, with the acid of a low-frequency alternating magnetic field (200 Hz), the actin cytoskeleton-targeting nanofibers could induce severe actin disruption, leading to a remarkable cell cycle arrest and drastic cell death of tumor cells both in vitro and in vivo, but showed no obvious toxicity to normal cells. The actin cytoskeleton-targeting/disrupting supramolecular assembly implies an excellent strategy for realizing efficient cancer therapy.

Enhancing methanogenesis from anaerobic digestion of propionate with addition of Fe oxides supported on conductive carbon cloth.

In this study, a Fe2O3 supported on conductive carbon cloth (FC) was prepared and supplemented into anaerobic digestion reactors to improve propionate degradation. In the FC-supplemented reactors, the cumulative methane production and propionate degradation increased by 15.4% and 19.67% compared with those of the control, respectively. Less methane production with H2/CO2 as the sole substrate in the culture taken from the FC reactors suggested that interspecies hydrogen transfer in the FC reactors was weaker. These results suggested that direct interspecies electron transfer (DIET) was established in the FC reactors to improve the performance. Fe2O3 increased the secretion of electron shuttle components of extracellular polymeric substances to increase electron exchange capacity of biomass of the FC reactors, which further facilitated the DIET. Analysis on microbial communities confirmed that the abundance of microorganisms-related DIET in the FC reactors was higher than that in the control.

Two-dimensional supramolecular assemblies based on ß-cyclodextrin-grafted graphene oxide for mitochondrial dysfunction and photothermal therapy.

ß-Cyclodextrin (CD)-grafted graphene oxide (GO) is an emerging drug carrier for human diseases therapy. Herein, we report two-dimensional nano-supramolecular assemblies to specifically target and disrupt tumor cell mitochondria in a photocontrollable manner. Moreover, the nanoassemblies displayed extremely high near-infrared-induced photothermal efficiency.

Graphene oxide significantly inhibits cell growth at sublethal concentrations by causing extracellular iron deficiency.

Graphene oxide (GO)-based materials are increasingly being used in medical materials and consumer products. However, their sublethal effects on biological systems are poorly understood. Here, we report that GO (at 10 to 160 mg/L) induced significant inhibitory effects on the growth of different unicellular organisms, including eukaryotes (i.e. Saccharomyces cerevisiae, Candida albicans, and Komagataella pastoris) and prokaryotes (Pseudomonas fluorescens). Growth inhibition could not be explained by commonly reported cytotoxicity mechanisms such as plasma membrane damage or oxidative stress. Based on transcriptomic analysis and measurement of extra- and intracellular iron concentrations, we show that the inhibitory effect of GO was mainly attributable to iron deficiency caused by binding to the O-functional groups of GO, which sequestered iron and disrupted iron-related physiological and metabolic processes. This inhibitory mechanism was corroborated with supplementary experiments, where adding bathophenanthroline disulfonate-an iron chelating agent-to the culture medium exerted similar inhibition, whereas removing surface O-functional groups of GO decreased iron sequestration and significantly alleviated the inhibitory effect. These findings highlight a potential indirect detrimental effect of nanomaterials (i.e. scavenging of critical nutrients), and encourage research on potential biomedical applications of GO-based materials to sequester iron and enhance treatment of iron-dependent diseases such as cancer and some pathogenic infections.

Purification and characterization of biosurfactant produced by Bacillus licheniformis Y-1 and its application in remediation of petroleum contaminated soil.

In our previous research, a petroleum degrading bacteria strain Bacillus licheniformis Y-1 was obtained in Dagang Oilfield which had the capability of producing biosurfactant. This biosurfactant was isolated and purified in this work. The biosurfactant produced by strain Y-1 had the capability to decrease the surface tension of water from 74.66 to 27.26mN/m, with the critical micelle concentration (CMC) of 40mg/L. The biosurfactant performed not only excellent stabilities against pH, temperature and salinity, but also great emulsifying activities to different kinds of oil, especially the crude oil. According to the results of FT-IR spectrum and (1)H NMR spectrum detection, the surfactant was determined to be a cyclic lipopeptide. Furthermore, through the addition of surfactant, the effect of petroleum contaminated soil remediation by fungi got a significant improvement.

[Effect of CCH1 or MID1 gene disruption on drug tolerance and pathogenesis of Candida albicans].

The calcium gate encoded by CCH1 and MID1 genes is the main channel for external calcium absorption. As one of the important secondary messengers, the elevation of calcium concentration could activate some pathways to take part in various cell processes. In this study, we used CCH1 and MID1 mutant strains and also constructed their complementary strains to study the effect of drug tolerance and virulence of Candida albicans after CCH1 or MID1 deletion. By drug plate sensitivity assay and the broth microdilution method, we compared the changes between different strains. Moreover, we added calcium channel blocker and inhibitors to analyze the effect of calcium concentration on drug action. After the deletion of CCH1 or MID1 gene, the strain exhibited an obvious sensitivity to FLUC and ITRA, and the drug action was regulated by the calcium concentration. In a mouse model of intravenous infection, we found that attenuated virulence of cch1delta/delta or mid1delta/delta strain is specifically due to a loss of CCH1 or MID1 gene.