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The micelles of a poly(ε-caprolactone)-b-poly(ethylene oxide) block copolymer (PCL 59 -b-PEO 113 ) in different mixed solvents were held at 53 °C for 5 min, and seed solutions with different micellar morphologies and amounts of micellar semicrystalline seeds were prepared. The crystallinity of these seed micelles was identified by high-resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED). It is found that mostly amorphous spherical micelles are formed by heating micellar solutions in H 2 O/THF (5/1 v/v) and H 2 O/dioxane (5/1 v/v) mixed solvents, a mixture of amorphous spherical micelles and short semicrystalline cylindrical micelles is yielded in H 2 O/DMF (5/1 v/v), whereas mostly short semicrystalline cylindrical micelles are obtained in H 2 O/DMSO (5/1 v/v) mixed solvent. The seed solutions were placed at 4 °C for micellar growth. Transmission electron microscope (TEM) shows that micellar growth driven by epitaxial crystallization of core-forming PCL chains takes place and the length of grown cylindrical micelles increases with time. Two growth modes are observed. One is the growth of unimers (or amorphous spherical micelles) on the active ends of semicrystalline cylindrical micelles in micellar solution in H 2 O/DMF (5/1 v/v) at the initial growth period. The other is the growth by end-to-end coupling of cylindrical micelles in H 2 O/DMSO (5/1 v/v). The kinetics of micellar growth is strongly dependent on the growth mechanism. The growth of the cylindrical micelles in the H 2 O/DMF (5/1 v/v) solution is much faster than that in the H 2 O/DMSO (5/1 v/v) solution. On long time scale, micellar growth by end-to-end coupling of semicrystalline cylindrical micelles occurs with slow rate in both H 2 O/DMF (5/1 v/v) and H 2 O/DMSO (5/1 v/v) solutions, and the growth rate in H 2 O/DMF (5/1 v/v) solution is even slower than that in H 2 O/DMSO (5/1 v/v).

To obtain ideal sensing materials with nearly zero temperature coefficient resistance (TCR) for self-temperature-compensated pressure sensors, we proposed an Incipient Network Conformal Growth (INCG) technology to prepare hybrid and elastic porous materials: the nanoparticles (NPs) are first dispersed in solvent to form an incipient network, another component is then introduced to coat the incipient network conformally via wet chemical route. The conformal coatings not only endow NPs with high stability but also offer them additional structural elasticity, meeting requirements for future generations of portable, compressive and flexible devices. The resultant polypyrrole/silver coaxial nanowire hybrid aero-sponges prepared via INCG technology have been processed into a piezoresistive sensor with highly sensing stability (low TCR 0.86 × 10(-3)/°C), sensitivity (0.33 kPa(-1)), short response time (1 ms), minimum detectable pressure (4.93 Pa) after suffering repeated stimuli, temperature change and electric heating. Moreover, a stress-triggered Joule heater can be also fabricated mainly by the PPy-Ag NW hybrid aero-sponges with nearly zero temperature coefficient.

As a result of inherent rigidity of the conjugated macromolecular chains resulted from the delocalized π-electron system along the polymer backbone, it has been a huge challenge to make conducting polymer hydrogels elastic by far. Herein elastic and conductive polypyrrole hydrogels with only conducting polymer as the continuous phase have been simply synthesized in the indispensable conditions of 1) mixed solvent, 2) deficient oxidant, and 3) monthly secondary growth. The elastic mechanism and oxidative polymerization mechanism on the resulting PPy hydrogels have been discussed. The resulting hydrogels show some novel properties, e.g., shape memory elasticity, fast functionalization with various guest objects, and fast removal of organic infectants from aqueous solutions, all of which cannot be observed from traditional non-elastic conducting polymer counterparts. What's more, light-weight, elastic, and conductive organic sponges with excellent stress-sensing behavior have been successfully achieved via using the resulting polypyrrole hydrogels as precursors.

Lysosomes have recently been identified as important apoptotic signal integrators in response to various stimuli. Here we report the functional characterization of LAPF, a novel lysosome-associated apoptosis-inducing protein containing PH and FYVE domains. LAPF is a representative of a new protein family, the Phafins (protein containing both PH and FYVE domains), which consists of 14 unidentified proteins from various species. Overexpression of LAPF in L929 cells induces apoptosis and also increases cell sensitivity to TNF␣-induced apoptosis, concomitant with its translocation to lysosomes. Two mutants of LAPF, either lacking the PH or FYVE domain, failed to induce cell death and translocate to lysosomes, suggesting that both domains are required for its apoptosis-inducing activity and relocation. We demonstrate that LAPF may induce apoptosis via the following steps: LAPF translocation to lysosomes, lysosomal membrane permeabilization (LMP), release of cathepsin (cath) D and L, mitochondrial membrane permeabilization (MMP), release of apoptosis-inducing factor (AIF), and caspase-independent apoptosis. The cath D-specific inhibitor attenuates LAPF-induced apoptosis, indicating a pivotal role of lysosomes in LAPFinitiated apoptosis. We also demonstrate that the lysosomal pathway was employed in the typical apoptotic model in which high dose TNF␣ was used to stimulate L929 cells. Silencing of LAPF expression by small RNA interference protected L929 cells from hTNF␣-induced apoptosis by impairing hTNF␣-triggered LMP and MMP. Therefore, LAPF may launch caspase-independent apoptosis through the lysosomal-mitochondrial pathway.Apoptosis can be induced either through the extrinsic pathway, initiated by the ligation of death receptors, or the intrinsic pathway, triggered by perturbation of intracellular homeostasis (1, 2). Both pathways converge on a common "central executioner," a self-amplifying mechanism that involves mitochondrial membrane permeabilization (MMP) 2 and/or caspase activation cascades (3-5). Despite the central role of mitochondria in apoptosis, mounting evidence suggests that other organelles, including lysosomes, the endoplasmic reticulum, and the Golgi apparatus, are also points of pro-apoptotic signaling integration (1). Recent studies have shown that lysosomal membrane permeabilization (LMP) is an early and, perhaps, initiating event in apoptosis triggered by ligation of death receptors, lysosomotropic agents, oxidative stresses, or serum withdrawal (6 -9). The specific release of cathepsins from lysosomes into the cytosol is critical for lysosome-mediated cell death and is responsible for activation of downstream signal pathways. Cathepsins can indirectly induce MMP by modifying cytosolic proteins, including Bax, Bak, or Bid, conferring upon them the ability to translocate to the outer mitochondrial membrane, and can also directly activate effector caspases, in particular caspase-3 (2, 7, 10, 11). However, direct activation of caspases is controversial because other investigators (2, 12) hold oppo...

Sepsis is the principal cause of fatality in the intensive care units worldwide. It involves uncontrolled inflammatory response resulting in multi-organ failure and even death. Micheliolide (MCL), a sesquiterpene lactone, was reported to inhibit dextran sodium sulphate (DSS)-induced inflammatory intestinal disease, colitis-associated cancer and rheumatic arthritis. Nevertheless, the role of MCL in microbial infection and sepsis is unclear. We demonstrated that MCL decreased lipopolysaccharide (LPS, the main cell wall component of Gram-negative bacteria)-mediated production of cytokines (IL-6, TNF-α, MCP-1, etc) in Raw264.7 cells, primary macrophages, dendritic cells and human monocytes. MCL plays an anti-inflammatory role by inhibiting LPS-induced activation of NF-κB and PI3K/Akt/p70S6K pathways. It has negligible impact on the activation of mitogen-activated protein kinase (MAPK) pathways. In the acute peritonitis mouse model, MCL reduced the secretion of IL-6, TNF-α, IL-1β, MCP-1, IFN-β and IL-10 in sera, and ameliorated lung and liver damage. MCL down-regulated the high mortality rate caused by lethal LPS challenge. Collectively, our data illustrated that MCL enabled maintenance of immune equilibrium may represent a potentially new anti-inflammatory and immunosuppressive drug candidate in the treatment of sepsis and septic shock.

The effect of inorganic salt at concentrations typical of a biological environment on the micellar morphology of semicrystalline PCL‐b‐PEO in aqueous solution is investigated. The salt is introduced either by dialysis of a THF solution against an aqueous solution of the salt or by adding it into an aqueous solution containing preformed micelles. The inorganic salt can induce sphere‐to‐rod or sphere‐to‐lamella transformations of the PCL‐b‐PEO micelles in aqueous solution, depending on the length of the PCL block. The inorganic salt induces “salting‐out” of the PEO block, leading to a decrease in the reduced tethering density of the corona in the micelles.