Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune receptor expressed in microglia in the brain. A soluble form of TREM2 (sTREM2) derived from proteolytic cleavage of the ...cell surface receptor is increased in the preclinical stages of AD and positively correlates with the amounts of total and phosphorylated tau in the cerebrospinal fluid. However, the physiological and pathological functions of sTREM2 remain unknown. Here, we show that sTREM2 promotes microglial survival in a PI3K/Akt-dependent manner and stimulates the production of inflammatory cytokines depending on NF-κB. Variants of sTREM2 carrying AD risk-associated mutations were less potent in both suppressing apoptosis and triggering inflammatory responses. Importantly, sTREM2 delivered to the hippocampi of both wild-type and
-knockout mice elevated the expression of inflammatory cytokines and induced morphological changes of microglia. Collectively, these data indicate that sTREM2 triggers microglial activation inducing inflammatory responses and promoting survival. This study has implications for the pathogenesis of AD and provides insights into targeting sTREM2 pathway for AD therapy.
Due to their high adsorption capacities, carbon-based nanomaterials such as carbon nanotubes, activated carbons, fullerene and graphene are widely used as the currently most promising functional ...materials. Since its discovery in 2004, graphene has exhibited great potential in many technological fields, such as energy storage materials, supercapacitors, resonators, quantum dots, solar cells, electronics, and sensors. The large theoretical specific surface area of graphene nanosheets (2630m2·g−1) makes them excellent candidates for adsorption technologies. Further, graphene nanosheets could be used as substrates for decorating the surfaces of nanoparticles, and the corresponding nanocomposites could be applied as novel adsorbents for the removal of low concentrated contaminants from aqueous solutions. Therefore, graphene nanosheets will challenge the current existing adsorbents, including other types of carbon-based nanomaterials.
•The recent progress of application of graphene in adsorption was presented.•The design and practical application of graphene based composites was discussed.•The future trends and prospects of graphene were analyzed and proposed.
Using the high‐time‐resolution data from the Magnetospheric Multiscale mission, precursor waves upstream of foreshock transient (FT) shocks are statistically investigated using the four‐spacecraft ...timing method. The wave frequencies and wave vectors determined in the plasma rest frame (PRF) are shown to follow the cold plasma dispersion relation for whistler waves. Combining with the feature of the right‐hand polarization in the PRF, the precursors are identified as whistler‐mode waves around the lower hybrid frequency. The occurrence of whistler precursors is independent of the Alfvén Mach number and the FT shock normal angle. More importantly, all the whistler precursors have group velocities pointing upstream in the shock frame, suggesting the dispersive radiation to be a possible generation mechanism. The study improves the understanding of not only the whistler precursors but also the overall FT shock dynamics.
Plain Language Summary
The characteristics of the precursor waves upstream of foreshock transient (FT) shocks are determined in the plasma rest frame using the multi‐point measurements from the Magnetospheric Multiscale mission with appropriate separation scales. The statistical results demonstrate for the first time that the precursors upstream of FT shocks are lower hybrid frequency whistler‐mode waves. The presence or absence of large amplitude whistler precursors does not depend on the FT shock normal angle and the Alfvén Mach number. These results have important implications on the nature of the whistler precursors and the dynamics of the FT shocks.
Key Points
Precursor waves upstream of foreshock transient shocks are found to follow the whistler wave dispersion relation in the plasma rest frame
The occurrence of whistler precursors is independent of the Alfvén Mach numbers and normal angles of the foreshock transient shocks
The observed wave characteristics are consistent with that the precursors are generated through the dispersive radiation mechanism
Mortality from hepatitis B virus (HBV)–related acute‐on‐chronic liver failure (ACLF) is high due to limited treatment options. Preclinical and clinical investigations have proved that treatment with ...mesenchymal stromal cells (MSCs) is beneficial for recovery from liver injury. We hypothesized that the outcome of HBV‐related ACLF would be improved by MSC treatment. From 2010 to 2013, 110 patients with HBV‐related ACLF were enrolled in this open‐label, nonblinded randomized controlled study. The control group (n = 54) was treated with standard medical therapy (SMT) only. The experimental group (n = 56) was infused weekly for 4 weeks with 1.0 to 10 × 105 cells/kg allogeneic bone marrow–derived MSCs and then followed for 24 weeks. The cumulated survival rate of the MSC group was 73.2% (95% confidence interval 61.6%‐84.8%) versus 55.6% (95% confidence interval 42.3%‐68.9%) for the SMT group (P = 0.03). There were no infusion‐related side effects, but fever was more frequent in MSC compared to SMT patients during weeks 5‐24 of follow‐up. No carcinoma occurred in any trial patient in either group. Compared with the control group, allogeneic bone marrow–derived MSC treatment markedly improved clinical laboratory measurements, including serum total bilirubin and Model for End‐Stage Liver Disease scores. The incidence of severe infection in the MSC group was much lower than that in the SMT group (16.1% versus 33.3%, P = 0.04). Mortality from multiple organ failure and severe infection was higher in the SMT group than in the MSC group (37.0% versus 17.9%, P = 0.02). Conclusion: Peripheral infusion of allogeneic bone marrow–derived MSCs is safe and convenient for patients with HBV‐related ACLF and significantly increases the 24‐week survival rate by improving liver function and decreasing the incidence of severe infections. (Hepatology 2017;66:209–219).
It is well known that high-risk human papilloma virus (HR-HPV) infection is strongly associated with cervical cancer and E7 was identified as one of the key initiators in HPV-mediated carcinogenesis. ...Here we show that lactate dehydrogenase A (LDHA) preferably locates in the nucleus in HPV16-positive cervical tumors due to E7-induced intracellular reactive oxygen species (ROS) accumulation. Surprisingly, nuclear LDHA gains a non-canonical enzyme activity to produce α-hydroxybutyrate and triggers DOT1L (disruptor of telomeric silencing 1-like)-mediated histone H3K79 hypermethylation, resulting in the activation of antioxidant responses and Wnt signaling pathway. Furthermore, HPV16 E7 knocking-out reduces LDHA nuclear translocation and H3K79 tri-methylation in K14-HPV16 transgenic mouse model. HPV16 E7 level is significantly positively correlated with nuclear LDHA and H3K79 tri-methylation in cervical cancer. Collectively, our findings uncover a non-canonical enzyme activity of nuclear LDHA to epigenetically control cellular redox balance and cell proliferation facilitating HPV-induced cervical cancer development.
With advantages such as high theoretical capacity, low cost, and nontoxicity, Zn metal has been widely investigated as an anode for aqueous batteries. However, the problems of dendrite formation and ...sustained corrosion originating from severe interfacial side reactions and uncontrolled Zn electrodeposition in aqueous electrolytes significantly slows down the practical application of Zn metal anodes. To address these issues, herein, an anti‐corrosion elastic constraint (AEC) is introduced that is built with nanosized TiO2 and polyvinylidene fluoride (PVDF) matrix to Zn anode, where the PVDF layer serves as an elastic H2O/O2‐blocking layer and the decorated TiO2 nanoparticles assist uniform Zn electrodeposition. With this corrosion‐inhibition and electrodeposition‐redirection coating, the electrodeposition consistency and thermodynamic stability of the Zn anode are significantly improved, enabling a long‐term stable plating/stripping performance for 2000 h with an ultralow overpotential (<50 mV) and a high average Coulombic efficiency (>99.4%) for 1000 cycles without obvious dendrite formation. Even at a high current density of 8.85 mA cm−2 with limited Zn supply (DODZn = 60%), stable Zn deposition is achieved over 250 h. When coupled with a MnO2 cathode, the AEC‐Zn anode shows a remarkably enhanced full‐cell cycling stability, indicative of high reliability of aqueous Zn batteries for practical application.
An anti‐corrosion elastic constraint is developed to redirect the Zn electrodeposition for aqueous zinc‐ion batteries. With this corrosion‐inhibition and electrodeposition‐redirection coating, the electrodeposition consistency and thermodynamic stability of Zn anodes are significantly improved, enabling a long‐term stable plating/stripping performance for 2000 h with an ultralow overpotential (<50 mV) and a high Coulombic efficiency (>99.4%) for 1000 cycles.
Although photodynamic therapy (PDT) has served as an important strategy for treatment of various diseases, it still experiences many challenges, such as shallow penetration of light, high‐dose light ...irradiation, and low therapy efficiency in deep tissue. Here, a low‐dose X‐ray‐activated persistent luminescence nanoparticle (PLNP)‐mediated PDT nanoplatform for depth‐independent and repeatable cancer treatment has been reported. In order to improve therapeutic efficiency, this study first synthesizes W(VI)‐doped ZnGa2O4:Cr PLNPs with stronger persistent luminescence intensity and longer persistent luminescence time than traditional ZnGa2O4:Cr PLNPs. The proposed PLNPs can serve as a persistent excitation light source for PDT, even after X‐ray irradiation has been removed. Both in vitro and in vivo experiments demonstrate that low‐dose (0.18 Gy) X‐ray irradiation is sufficient to activate the PDT nanoplatform and causes significant inhibitory effect on tumor progression. Therefore, such PDT nanoplatform will provide a promising depth‐independent treatment mode for clinical cancer therapy in the future.
Low‐dose X‐ray activated persistent luminescence nanoparticle (PLNP)‐mediated photodynamic therapy (PDT) nanoplatform is fabricated based on W(VI)‐doped ZnGa2O4:Cr (ZGO:Cr/W) nanoparticles. Due to the superior persistent luminescence performance of ZGO:Cr/W PLNPs, this PDT nanoplatform significantly reduces the X‐ray dosage (0.18 Gy) both in vitro and in vivo, and also improves PDT efficiency in deep tissue.
Immunity deteriorates with age in animals but comparatively little is known about the temporal regulation of plant resistance to herbivores. The phytohormone jasmonate (JA) is a key regulator of ...plant insect defense. Here, we show that the JA response decays progressively in Arabidopsis. We show that this decay is regulated by the miR156-targeted SQUAMOSA PROMOTER BINDING PROTEIN-LIKE9 (SPL9) group of proteins, which can interact with JA ZIM-domain (JAZ) proteins, including JAZ3. As SPL9 levels gradually increase, JAZ3 accumulates and the JA response is attenuated. We provide evidence that this pathway contributes to insect resistance in young plants. Interestingly however, despite the decay in JA response, older plants are still comparatively more resistant to both the lepidopteran generalist Helicoverpa armigera and the specialist Plutella xylostella, along with increased accumulation of glucosinolates. We propose a model whereby constitutive accumulation of defense compounds plays a role in compensating for age-related JA-response attenuation during plant maturation.
Alternative technologies are required in order to meet a worldwide demand for clean non-polluting energy sources. Thermoelectric generators, which generate electricity from heat in a compact and ...reliable manner, are potential devices for waste heat recovery. However, thermoelectric performance, as encapsulated by the figure of merit ZT, has remained at around 1.0 at room temperature, which has limited practical applications. Here, we study the effects of pressure on ZT in Cr-doped PbSe, which has a maximum ZT of less than 1.0 at a temperature of about 700 K. By applying external pressure using a diamond anvil cell, we obtained a room-temperature ZT value of about 1.7. From thermoelectric, magnetoresistance and Raman measurements, as well as density functional theory calculations, a pressure-driven topological phase transition is found to enable this enhancement. Experiments also support the appearance of a topological crystalline insulator after the transition. These findings point to the possibility of using compression to increase not just ZT in existing thermoelectric materials, but also the possibility of realizing topological crystalline insulators.
A Mn(III)‐mediated radical cyclization reaction of o‐vinylaryl isocyanides and arylboronic acids or diphenylphosphine oxides to access various 2‐functionalized quinolines under mild conditions was ...developed. With the introduction of radical stabilizing substituents (e. g. aryl and methyl group) on vinyl group, this reaction provides a regiospecific 6‐endo‐trig radical cyclization of o‐vinylaryl isocyanides, giving a number of structurally unique and biologically potential 2‐functionalized quinoline derivatives.
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