Enabling Highly Robust Full-Color Ultralong Room-Temperature Phosphorescence and Stable White Organic Afterglow from Polycyclic Aromatic Hydrocarbons.

In this work, full-color and stable white organic afterglow materials with outstanding water, organic solvents, and temperature resistances have been developed for the first time by embedding the selected polycyclic aromatic hydrocarbons into melamine-formaldehyde polymer via solution polymerization. The afterglow quantum yields and lifetimes of the resulting polymer films were up to 22.7 % and 4.83 s, respectively, under ambient conditions. For the coronene-doped sample, its afterglow color could be linearly tuned between yellow and blue by adjusting the temperature, and it could still emit an intense blue afterglow with a lifetime of 0.68 s at 440 K. Moreover, the films showed a bright and stable white afterglow at 370 K with a lifetime of 2.80 s and maintained an excellent afterglow performance after soaking in water and organic solvents for more than 150 days. In addition, the application potential of the polymer films in information encryption and anti-counterfeiting was also demonstrated.

SIRT6 regulates obesity-induced oxidative stress via ENDOG/SOD2 signaling in the heart.

The sirtuin 6 (SIRT6) participates in regulating glucose and lipid homeostasis. However, the function of SIRT6 in the process of cardiac pathogenesis caused by obesity-associated lipotoxicity remains to be unveiled. This study was designed to elucidate the role of SIRT6 in the pathogenesis of cardiac injury due to nutrition overload-induced obesity and explore the downstream signaling pathways affecting oxidative stress in the heart. In this study, we used Sirt6 cardiac-specific knockout murine models treated with a high-fat diet (HFD) feeding to explore the function and mechanism of SIRT6 in the heart tissue during HFD-induced obesity. We also took advantage of neonatal cardiomyocytes to study the role and downstream molecules of SIRT6 during HFD-induced injury in vitro, in which intracellular oxidative stress and mitochondrial content were assessed. We observed that during HFD-induced obesity, Sirt6 loss-of-function aggravated cardiac injury including left ventricular hypertrophy and lipid accumulation. Our results evidenced that upon increased fatty acid uptake, SIRT6 positively regulated the expression of endonuclease G (ENDOG), which is a mitochondrial-resident molecule that plays an important role in mitochondrial biogenesis and redox homeostasis. Our results also showed that SIRT6 positively regulated superoxide dismutase 2 (SOD2) expression post-transcriptionally via ENDOG. Our study gives a new sight into SIRT6 beneficial role in mitochondrial biogenesis of cardiomyocytes. Our data also show that SIRT6 is required to reduce intracellular oxidative stress in the heart triggered by high-fat diet-induced obesity, involving the control of ENDOG/SOD2.

Switchable and Highly Robust Ultralong Room-Temperature Phosphorescence from Polymer-Based Transparent Films with Three-Dimensional Covalent Networks for Erasable Light Printing.

In this work, an efficient polymer-based organic afterglow system, which shows reversible photochromism, switchable ultralong organic phosphorescence (UOP), and prominent water and chemical resistance simultaneously, has been developed for the first time. By doping phenoxazine (PXZ) and 10-ethyl-10H-phenoxazine (PXZEt) into epoxy polymers, the resulting PXZ@EP-0.25 % and PXZEt@EP-0.25 % films show unique photoactivated UOP properties, with phosphorescence quantum yields and lifetimes up to 10.8 % and 845 ms, respectively. It is found that the steady-state luminescence and UOP of PXZ@EP-0.25 % are switchable by light irradiation and thermal annealing. Moreover, the doped films can still produce conspicuous UOP after soaking in water, strong acid and base, and organic solvents for more than two weeks, exhibiting outstanding water and chemical resistance. Inspired by these exciting results, the PXZ@EP-0.25 % has been successfully exploited as an erasable transparent film for light printing.

Metformin alleviates HFD-induced oxidative stress in hepatocyte via activating SIRT6/PGC-1α/ENDOG signaling.

Metformin is accepted as a first-line drug for the therapy of Type 2 diabetes (T2D), while its mechanism is still controversial. In the present study, by taking advantage of mouse model of high-fat-diet (HFD)-induced obesity and primary mouse hepatocytes (PMHCs) as well as human hepatocyte L02 cell line, we aimed to investigate the involvement of SIRTs during the application of metformin for the therapy of T2D. Our data evidenced that during HFD-induced obesity, there was elevation of nucleus protein acetylation. Analysis of liver tissue showed that among all SIRT members, SIRT6 expression was significantly down-regulated during HFD feeding, which was sustained to regular level with metformin administration. Our result also showed that SIRT6 suppressed intracellular oxidative stress upon FAs stimulation in PMHCs and L02 cells. Mechanistically, SIRT6, but not SIRT1 promoted PGC-1α expression. We further prove that ENDOG is downstream of PGC-1α. In addition, we evidenced that ENDOG protects hepatocytes from lipid-induced oxidative stress, and down-regulation of Endog blunted the protective role of metformin in defending against FAs-induced oxidative stress. Our study established a novel mechanism of metformin in counteracting lipid-induced hepatic injury via activating SIRT6/PGC-1α/ENDOG signaling, thus providing novel targets of metformin in the therapy of T2D.

IL-6 protects cardiomyocytes from oxidative stress at the early stage of LPS-induced sepsis.

Pro-inflammatory cytokines play important roles in sepsis-induced cardiac injury. Among various cytokines, the function of Interleukin-6 (IL-6) in the regulation of cardiomyocyte injury remains to be elucidated. This study aimed to investigate whether IL-6 plays a key role in the sepsis-induced cardiomyocyte injury and the possible mechanism. Mice deficient for Il-6 exhibited impaired heart rhythm after LPS stimulation. Histological analysis revealed significantly increased oxidative stress after LPS stimulation in the heart with Il-6 knockout. On the contrary, IL-6 supplementation alleviated LPS-induced oxidative stress. Mechanically, IL-6 facilitates Nrf2 expression and its nucleus translocation, which subsequently promotes the expression of antioxidant genes and sustains redox homeostasis in cardiomyocytes, and Nrf2 deletion results in elevated oxidative stress during LPS stimulation and cannot be inverted by IL-6 supplement. Our study presents a new sight for the protective role of IL-6 during the pathological development of LPS-induced cardiac injury, which functions as an anti-oxidant molecule via activating Nrf2 signaling.

Transcriptomic analyses reveal the pathways associated with the volatilization and resistance of mercury(II) in the fungus Lecythophora sp. DC-F1.

The biotic enzymatic reduction of mercury II [Hg(II)] to elemental Hg [Hg(0)] is an important pathway for Hg detoxification in natural ecosystems. However, the mechanisms of Hg(II) volatilization and resistance in fungi have not been understood completely. In the present study, we investigated the mechanisms of Hg(II) volatilization and resistance in the fungus Lecythophora sp. DC-F1. Hg(II) volatilization occurred during the investigation via the reduction of Hg(II) to Hg(0) in DC-F1. Comparative transcriptome analyses of DC-F1 revealed 3439 differentially expressed genes under 10 mg/L Hg(II) stress, among which 2770 were up-regulated and 669 were down-regulated. Functional enrichment analyses of genes and pathways further suggested that the Hg(II) resistance of DC-F1 is a multisystem collaborative process with three important transcriptional responses to Hg(II) stress: a mer-mediated Hg detoxification system, a thiol compound metabolism, and a cell reactive oxygen species stress response system. The phylogenetic analysis of merA protein homologs suggests that the Hg(II) reduction by merA is widely distributed in fungi. Overall, this study provides evidence for the reduction of Hg(II) to Hg(0) in fungi via the mer-mediated Hg detoxification system and offers a comprehensive explanation for its role within Hg biogeochemical cycling. These findings offer a strong theoretical basis for the application of fungi in the bioremediation of Hg-contaminated envionments.

AKT2 regulates development and metabolic homeostasis via AMPK-depedent pathway in skeletal muscle.

Skeletal muscle is responsible for the majority of glucose disposal in the body. Insulin resistance in the skeletal muscle accounts for 85-90% of the impairment of total glucose disposal in patients with type 2 diabetes (T2D). However, the mechanism remains controversial. The present study aims to investigate whether AKT2 deficiency causes deficits in skeletal muscle development and metabolism, we analyzed the expression of molecules related to skeletal muscle development, glucose uptake and metabolism in mice of 3- and 8-months old. We found that AMP-activated protein kinase (AMPK) phosphorylation and myocyte enhancer factor 2 (MEF2) A (MEF2A) expression were down-regulated in AKT2 knockout (KO) mice, which can be inverted by AMPK activation. We also observed reduced mitochondrial DNA (mtDNA) abundance and reduced expression of genes involved in mitochondrial biogenesis in the skeletal muscle of AKT2 KO mice, which was prevented by AMPK activation. Moreover, AKT2 KO mice exhibited impaired AMPK signaling in response to insulin stimulation compared with WT mice. Our study establishes a new and important function of AKT2 in regulating skeletal muscle development and glucose metabolism via AMPK-dependent signaling.

The bioremediation potentials and mercury(II)-resistant mechanisms of a novel fungus Penicillium spp. DC-F11 isolated from contaminated soil.

Bioremediation of Hg-contaminated soil using microbe-based strategies is a promising and efficient method as it is inexpensive and not harmful to the environment. In this study, a novel Hg(II)-volatilizing fungus Penicillium spp., DC-F11 was isolated and showed bioremediation potential for reducing Hg(II) phytotoxicity, total Hg, and exchangeable Hg in Hg(II)-polluted soil. Subsequently, the mechanisms of Hg(II) volatilization and resistance involved were investigated using multiple complementary techniques. The fungal cells could detoxify Hg(II) by extracellular sequestration via adsorption and precipitation. Moreover, a comparative transcriptome analysis uncovered the primary intracellular adaptive responses of the DC-F11 to Hg(II) stress, including mer-mediated detoxification system, thiol compound metabolism, and oxidative stress defense and damage repair metabolism. These results showed that the resistance of DC-F11 to Hg(II) was generally a multisystem collaborative process. Here, we report, for the first time, that the mer-mediated detoxification system was responsible for Hg(II) volatilization in fungus. These findings provide a better understanding of the mechanisms involved in Hg(II) volatilization and resistance that occur in fungi and also provide a strong theoretical basis for the future application of fungi in the bioremediation of Hg-polluted environments.

Reduction in Hg phytoavailability in soil using Hg-volatilizing bacteria and biochar and the response of the native bacterial community.

Biological approaches are considered promising and eco-friendly strategies to remediate Hg contamination in soil. This study investigated the potential of two 'green' additives, Hg-volatilizing bacteria (Pseudomonas sp. DC-B1 and Bacillus sp. DC-B2) and sawdust biochar, and their combination to reduce Hg(II) phytoavailability in soil and the effect of the additives on the soil bacterial community. The results showed that the Hg(II) contents in soils and lettuce shoots and roots were all reduced with these additives, achieving more declines of 12.3-27.4%, 24.8-57.8% and 2.0-48.6%, respectively, within 56 days of incubation compared to the control with no additive. The combination of DC-B2 and 4% biochar performed best in reducing Hg(II) contents in lettuce shoots, achieving a decrease of 57.8% compared with the control. Pyrosequencing analysis showed that the overall bacterial community compositions in the soil samples were similar under different treatments, despite the fact that the relative abundance of dominant genera altered with the additives, suggesting a relatively weak impact of the additives on the soil microbial ecosystem. The low relative abundances of Pseudomonas and Bacillus, close to the background levels, at the end of the experiment indicated a small biological disturbance of the local microbial niche by the exogenous bacteria.

Bioremediation of Hg-contaminated soil by combining a novel Hg-volatilizing Lecythophora sp. fungus, DC-F1, with biochar: Performance and the response of soil fungal community.

Reducing Hg contamination in soil using eco-friendly approaches has attracted increasing attention in recent years. In this study, a novel multi-metal-resistant Hg-volatilizing fungus belonging to Lecythophora sp., DC-F1, was isolated from multi-metal-polluted mining-area soil, and its performance in reducing Hg bioavailability in soil when used in combination with biochar was investigated. The isolate displayed a minimum inhibitory concentration of 84.5mg·L-1 for Hg(II) and volatilized >86% of Hg(II) from LB liquid medium with an initial concentration of 7.0mg·L-1 within 16h. Hg(II) contents in soils and grown lettuce shoots decreased by 13.3-26.1% and 49.5-67.7%, respectively, with DC-F1 and/or biochar addition compared with a control over 56days of incubation. Moreover, treatment with both bioagents achieved the lowest Hg content in lettuce shoots. Hg presence and DC-F1 addition significantly decreased the number of fungal ITS gene copies in soils. High-throughput sequencing showed that the soil fungal community compositions were more largely influenced by DC-F1 addition than by biochar addition, with the proportion of Mortierella increasing and those of Penicillium and Thielavia decreasing with DC-F1 addition. Developing the coupling of Lecythophora sp. DC-F1 with biochar into a feasible approach for the recovery of Hg-contaminated soils is promising.

Turning a Luffa Protein into a Self-Assembled Biodegradable Nanoplatform for Multitargeted Cancer Therapy.

The peptide-derived self-assembly platform has attracted increasing attention for its great potential to develop into multitargeting nanomedicines as well as its inherent biocompatibility and biodegradability. However, their clinical application potentials are often compromised by low stability, weak membrane penetrating ability, and limited functions. Herein, inspired by a natural protein from the seeds of Luffa cylindrica, we engineered via epitope grafting and structure design a hybrid peptide-based nanoplatform, termed Lupbin, which is capable of self-assembling into a stable superstructure and concurrently targeting multiple protein-protein interactions (PPIs) located in cytoplasm and nuclei. We showed that Lupbin can efficiently penetrate cell membrane, escape from early endosome-dependent degradation, and subsequently disassemble into free monomers with wide distribution in cytosol and nucleus. Importantly, Lupbin abrogated tumor growth and metastasis through concurrent blockade of the Wnt/ß-catenin signaling and reactivation of the p53 signaling, with a highly favorable in vivo biosafety profile. Our strategy expands the application of self-assembled nanomedicines into targeting intercellular PPIs, provides a potential nanoplatform with high stability for multitargeted cancer therapy, and likely reinvigorates the development of peptide-based therapeutics for the treatment of different human diseases including cancer.

Characterization of an Hg(II)-volatilizing Pseudomonas sp. strain, DC-B1, and its potential for soil remediation when combined with biochar amendment.

Hg contamination is a critical environmental problem, and its remediation using cost-effective and environmentally friendly methods is highly desirable. In this study, a multi-metal-resistant bacterium showing strong Hg(II) volatilization ability, Pseudomonas sp. DC-B1, was isolated from heavy metal-contaminated soils. DC-B1 volatilized 81.1%, 79.2% and 74.3% of the initial Hg2+ from culture solutions with initial Hg2+ concentrations of 5.1, 10.4, and 15.7 mg/L, respectively, within 24 h. Microcosm experiments were performed to investigate the remediation of Hg(II)-spiked soils inoculated with DC-B1 coupled with sawdust biochar amendment. The efficiency of Hg removal from two types of soil samples with different properties and an initial Hg(II) content of approximately 100 mg/kg was enhanced 5.7-13.1% by bio-augmentation with inoculation of the bacterial strain DC-B1, 5.4-10.7% by amendment of 4% (w/w) biochar, and 10.7-23.2% by the combination of DC-B1 and biochar amendments over an incubation period of 24 d over the efficiency in the control treatment under flooded conditions. Longer root lengths were observed in lettuce grown in the treated soils than in lettuce from the control soil, confirming the bioremediation efficacy of the two bioagents for soil Hg contamination.

Arginine-modified dual emission photoluminescent nanocrystals for bioimaging at subcellular resolution.

Bioimaging at a subcellular resolution to label cytoplasm and nucleus in living cell by just one photoluminescent nanoparticle has great application potential in bioresearch, preclinical diagnosis, screening, and image-guided therapy of life-threatening diseases. Herein, we report a novel arginine (Arg) functionalized ultra-small lanthanide oxyfluoride nanocrystals (LaOF) for simultaneously targeted imaging cell cytoplasm and nucleus. As-prepared Arg-modified PAA capped LaOF: 45%Ce, 15%Tb nanocrystals (LaOF:Ce,Tb@PAA@Arg) possessed high water dispersibility, ultra-small size (∼5.7 nm) and double emissions (green and red) with high quantum yield (40%). Such functionalized nanocrystals presented high cellular biocompatibility and were successfully used to label living cells with very high contrast. These functionalized nanocrystals also exhibited significantly higher photostability and brightness as compared to commercial dyes. Such the ultra-small size, high photostability and intensity, double emissions, excellent biocompatibility and targeted ability, make as-prepared functionalized nanocrystals particularly promising for cellular and subcellular bioimaging applications.