No abstract

It is a great challenge to substantially improve the practical performance of flexible thermoelectric modules due to the absence of air-stable n-type thermoelectric materials with high-power factor. Here an excellent flexible n-type thermoelectric film is developed, which can be conveniently and rapidly prepared based on the as-grown carbon nanotube continuous networks with high conductivity. The optimum n-type film exhibits ultrahigh power factor of ∼1,500 μW m−1 K−2 and outstanding stability in air without encapsulation. Inspired by the findings, we design and successfully fabricate the compact-configuration flexible TE modules, which own great advantages compared with the conventional π-type configuration modules and well integrate the superior thermoelectric properties of p-type and n-type carbon nanotube films resulting in a markedly high performance. Moreover, the research results are highly scalable and also open opportunities for the large-scale production of flexible thermoelectric modules.

Our study highlights the overactivated neddylation pathway in lung cancer development and as a promising therapeutic target.

The cystic fibrosis transmembrane conductance regulator (CFTR) functions as an ATPase and as a chloride channel. It has been hypothesized, on the basis of electrophysiological findings, that the catalytic activity of CFTR is tightly coupled to the opening and closing of the channel gate. In the present study, to determine the structural basis for the ATPase activity of CFTR, we assessed the effect of mutations within the "Walker A" consensus motifs on ATP hydrolysis by the purified, intact protein. Mutation of the lysine residue in the "Walker A" motif of either the first nucleotide binding fold (CFTRK464A) or the second nucleotide binding fold (CFTRK1250A) inhibited the ATPase activity of the purified intact CFTR protein significantly, by greater than 50%. This finding suggests that the two nucleotide binding folds of CFTR are functioning cooperatively in catalysis. However, the rate of channel gating was only significantly inhibited in one of these purified mutants, CFTRK1250A, suggesting that ATPase activity may not be tightly coupled to channel gating as previously hypothesized.

Our results suggest that a novel TLR2/TLR4 heterodimer induced by Hb initiates inflammatory injury in ICH. Interfering with the assembly of the TLR2/TLR4 heterodimer may be a novel target for developing effective treatment of ICH.

Studies have shown that expression of cystic ®brosis transmembrane conductance regulator (CFTR) is associated with enhanced glutathione (GSH) ef¯ux from airway epithelial cells, implicating a role for CFTR in the control of oxidative stress in the airways. To de®ne the mechanism underlying CFTR-associated GSH¯ux, we studied wild-type and mutant CFTR proteins expressed in Sf9 membranes, as well as puri®ed and reconstituted CFTR. We show that CFTRexpressing membrane vesicles mediate nucleotide-activated GSH¯ux, which is disrupted in the R347D pore mutant, and in the Walker A K464A and K1250A mutants. Further, we reveal that puri®ed CFTR protein alone directly mediates nucleotide-dependent GSH¯ux. Interestingly, although ATP supports GSH ux through CFTR, this activity is enhanced in the presence of the non-hydrolyzable ATP analog AMP-PNP. These ®ndings corroborate previous suggestions that CFTR pore properties can vary with the nature of the nucleotide interaction. In conclusion, our data demonstrate that GSH¯ux is an intrinsic function of CFTR and prompt future examination of the role of this function in airway biology in health and disease.

Intracerebral hemorrhage (ICH) is a common type of fatal stroke, accounting for about 15% to 20% of all strokes. Hemorrhagic strokes are associated with high mortality and morbidity, and increasing evidence shows that innate immune responses and inflammatory injury play a critical role in ICH-induced neurological deficits. However, the signaling pathways involved in ICH-induced inflammatory responses remain elusive. Toll-like receptor 4 (TLR4) belongs to a large family of pattern recognition receptors that play a key role in innate immunity and inflammatory responses. In this review, we summarize recent findings concerning the involvement of TLR4 signaling in ICH-induced inflammation and brain injury. We discuss the key mechanisms associated with TLR4 signaling in ICH and explore the potential for therapeutic intervention by targeting TLR4 signaling.

Background and Purpose-Accumulating evidence indicates that inflammatory responses cause secondary injury after intracerebral hemorrhage (ICH). We recently demonstrated the involvement of toll-like receptor 4 (TLR4) signaling in these processes. The purpose of the current study was to investigate the protective effect and mechanism of TAK-242 (Ethyl (6R)-6-[N-(2-chloro-4-fluorophenyl) sulfamoyl] cyclohex-1-ene-1 -carboxylate, Takeda), a TLR4 antagonist, in an ICH mouse model. Methods-TAK-242 was intraperitoneally injected 6 hours after ICH once daily for 5 successive days. We assessed neurological deficit scores; changes in brain water content; and levels of inflammatory factors, DNA damage, and neuronal degeneration in perihematomal region 1, 3, and 5 days after ICH. Peripheral inflammatory cell infiltration was determined using flow cytometry; and the expression of TLR4 downstream signaling molecules was assessed by Western blot. Results-TAK-242 significantly reduced brain water content, neurological deficit scores, and levels of inflammatory factors.The levels of DNA damage and neuronal degeneration were also significantly decreased, as was peripheral inflammatory cell infiltration. The expression of TLR4 downstream signaling molecules, including myeloid differentiation primary response gene 88, toll/IR-1(TIR)-domain-containing adaptor protein inducing interferon-beta IκBα, nuclear factorκBp65, and phosphorylated nuclear factor-κBp65, was significantly downregulated. Conclusions-The