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Thiazoline-related innate fear-eliciting compounds (tFOs) orchestrate hypothermia, hypometabolism, and anti-hypoxia, which enable survival in lethal hypoxic conditions. Here, we show that most of these effects are severely attenuated in transient receptor potential ankyrin 1 (Trpa1) knockout mice. TFO-induced hypothermia involves the Trpa1-mediated trigeminal/vagal pathways and non-Trpa1 olfactory pathway. TFOs activate Trpa1-positive sensory pathways projecting from trigeminal and vagal ganglia to the spinal trigeminal nucleus (Sp5) and nucleus of the solitary tract (NTS), and their artificial activation induces hypothermia. TFO presentation activates the NTS-Parabrachial nucleus pathway to induce hypothermia and hypometabolism; this activation was suppressed in Trpa1 knockout mice. TRPA1 activation is insufficient to trigger tFO-mediated anti-hypoxic effects; Sp5/NTS activation is also necessary. Accordingly, we find a novel molecule that enables mice to survive in a lethal hypoxic condition ten times longer than known tFOs. Combinations of appropriate tFOs and TRPA1 command intrinsic physiological responses relevant to survival fate.

Because of the nontoxic solvents contained in CO 2 -in-water emulsions, porous polymer composites templated from these emulsions are conducive for bio-applications. Herein, bio-active rod-like calcium-organic framworks (Ca-BDC MOFs, BDC= 1,4-benzenedicarboxylate anion) particles co-stabilized CO 2 -in-water high internal phase emulsion (C/W HIPE) in the presence of polyvinyl alcohol (PVA) is first presented. After curing of the continuous phase, followed by releasing CO 2 , integral 3D macro-porous Ca-BDC monolith and Ca-BDC/Poly(2-hydroxyethyl methacrylate- co -acrylamide) HIPEs monolithic composites [Ca-BDC/P(AM- co -HEMA)HIPEs] with open-cell macro-porous structures were successfully prepared. The pore structure of these porous composite can be tuned by means of tailoring the Ca-BDC dosage, carbon dioxide pressure, and continuous phase volume fractions in corresponding C/W HIPEs. Results of bio-compatibility tests show that these Ca-BDC/P(AM- co -HEMA)HIPEs monoliths have non-cytotoxicity on HepG2 cells; also, the E. coli can grow either on the surfaces or inside these monoliths. Furthermore, immobilization of β -amylase on these porous composite presents that β -amylase can be well-anchored into the porous polymer composites, its catalytic activity can be maintained even after 10 cycles. This work combined bio-active MOFs Ca-BDC, bio-compatible open-cell macroporous polymer PAM- co -HEMA and green C/W HIPEs to present a novel and facile way to prepare interconnected macro-porous MOFs/polymer composites. Compared with the existing other well-known materials such as hydrogels, these porous composites possess well-defined tunable pore structures and superior bio-activity, thereby have promising applications in bio-tissue engineering, food, and pharmaceutical.

We systematically studied water adsorption and oxidation on the unreconstructed TiO 2 (001) surface using first-principles calculations. Water first adsorbs on the surface in a dissociative state and then in a molecular state, as water coverage increases. The geometric properties of all adsorption structures suggest that the dissociative water molecules can induce stress release of the (001) surface at low coverage, reducing reactivity of the surface and thus leading to molecular adsorption of water on the surface at high coverage. The adsorption energy (or the surface energy) monotonously increases (or decreases) with the increase of the coverage, which further confirms that water, irrespective of its dissociative or molecular state, can improve the stability of the (001) surface and reduce its activity. We deeply investigated the mechanism of the oxygen evolution reaction (OER) on the water-covered (001) surface. A new water-assisted OER pathway is identified on the (001) surface, which includes the sequential transfer of protons from molecular water and surface hydroxyls, and O-O coupling processes. During the OER pathway, the O-O coupling step exhibits the largest thermodynamic energy and highest energy barrier, clarifying that it is the rate-determining step in the whole pathway. Our findings provide new insights into the strong dependence of water adsorption modes on coverage for the anatase TiO 2 (001) surface and may explain the high oxidation activity of the TiO 2 (001) surface in aqueous environments typical of TiO 2 photocatalysis.

With the progress of medical technology, the development of new drugs and the improvement of the therapeutic effect of graft-versus host disease in the last two decades, the outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) have been greatly improved. However, graft failure is still a rare but serious complication of allo-HSCT. HLA incompatibility, virus infection, elderly donor, uncontrolled primary disease, damage of bone marrow hematopoietic microenvironment, ABO blood group incompatibility, T cell depletion, reduced intensity conditioning, and low nucleated cell number are all risk factors for graft failure. In recent years, with the implementation of HLA haplo-identical hematopoietic stem cell transplantation, the role of donor-specific antibodies in graft failure has attracted attention increasingly. This article reviews the recent studies involving the mechanism, risk factors and prevention measures of graft failure in allo-HSCT.

A novel clean method to synthesis a composite monolith was developed. Given its amphiphilic property, UiO-66 can emulsify water and CO 2 to format a high internal phase emulsion (HIPE) under certain conditions. These UiO-66-emulsified Pickering HIPEs can be used as templates to prepare interconnected macroporous MOF/polymer composite monoliths. The effects of UiO-66 amount, cross-linking agent concentration, and CO 2 -water ratio on UiO-66/PAM structures were investigated. Then, the as-synthesized MOF/PAM composites were characterized by TGA, XRD, SEM, and FT-IR analyses, as well as rheological and DMA measurements. The results indicated that the composites are interconnected with hierarchical pores, and the diameter of the voids is 10-50 μm. The directly prepared monoliths exhibited relatively high stresses at 82% strain and recovered their shape quickly. The adsorption capacity of the composites for methylene blue (MB) is 50 mg g -1 at a faster adsorption rate. The monoliths also exhibit underlying applications in edible oil-water separation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Sleep and wake have global effects on brain physiology, from molecular changes 1-4 and neuronal activities to synaptic plasticity 3-7 . Sleep-wake homeostasis is maintained by the generation of a sleep need that accumulates during waking and dissipates during sleep 8-11 . Here we investigate the molecular basis of sleep need using quantitative phosphoproteomic analysis of the sleep-deprived and Sleepy mouse models of increased sleep need. Sleep deprivation induces cumulative phosphorylation of the brain proteome, which dissipates during sleep. Sleepy mice, owing to a gain-of-function mutation in the Sik3 gene 12 , have a constitutively high sleep need despite increased sleep amount. The brain proteome of these mice exhibits hyperphosphorylation, similar to that seen in the brain of sleep-deprived mice. Comparison of the two models identifies 80 mostly synaptic sleep-need-index phosphoproteins (SNIPPs), in which phosphorylation states closely parallel changes of sleep need. SLEEPY, the mutant SIK3 protein, preferentially associates with and phosphorylates SNIPPs. Inhibition of SIK3 activity reduces phosphorylation of SNIPPs and slow wave activity during non-rapid-eye-movement sleep, the best known measurable index of sleep need, in both Sleepy mice and sleep-deprived wild-type mice. Our results suggest that phosphorylation of SNIPPs accumulates and dissipates in relation to sleep need, and therefore SNIPP phosphorylation is a molecular signature of sleep need. Whereas waking encodes memories by potentiating synapses, sleep consolidates memories and restores synaptic homeostasis by globally downscaling excitatory synapses 4-6 . Thus, the phosphorylation-dephosphorylation cycle of SNIPPs may represent a major regulatory mechanism that underlies both synaptic homeostasis and sleep-wake homeostasis.

Innate behaviors are genetically encoded, but their underlying molecular mechanisms remain largely unknown. Predator odor 2,4,5-trimethyl-3-thiazoline (TMT) and its potent analog 2-methyl-2-thiazoline (2MT) are believed to activate specific odorant receptors to elicit innate fear/defensive behaviors in naive mice. Here, we conduct a large-scale recessive genetics screen of ethylnitrosourea (ENU)-mutagenized mice. We find that loss of Trpa1, a pungency/irritancy receptor, diminishes TMT/2MT and snake skin-evoked innate fear/defensive responses. Accordingly, Trpa1 -/- mice fail to effectively activate known fear/stress brain centers upon 2MT exposure, despite their apparent ability to smell and learn to fear 2MT. Moreover, Trpa1 acts as a chemosensor for 2MT/TMT and Trpa1-expressing trigeminal ganglion neurons contribute critically to 2MT-evoked freezing. Our results indicate that Trpa1-mediated nociception plays a crucial role in predator odor-evoked innate fear/defensive behaviors. The work establishes the first forward genetics screen to uncover the molecular mechanism of innate fear, a basic emotion and evolutionarily conserved survival mechanism.

Mitochondrial DNA segregation is one of the characteristic modes of mitochondrial inheritance in which the heteroplasmic state of mitochondrial DNA is transmitted to the next generation in variable proportions. To analyze mitochondrial DNA segregation, we produced a heteroplasmic mouse strain with interspecific mitochondrial DNA haplotypes, which contains two types of mitochondrial DNA derived from C57BL/6J and Mus spretus strains. The strain was produced on a C57BL/6J nuclear genomic background by microinjection of donor cytoplasm into fertilized eggs. The PCR-RFLP semi-quantitative analysis method, which was improved to reduce the effect of heteroduplex formation, was used to measure the proportion of heteroplasmic mitochondrial DNA in tissues. Founder mice contained up to approximately 14% of exogenous Mus spretus mitochondrial DNA molecules in their tails, and the detected proportions differed among tissues of the same individual. Heteroplasmic mitochondrial DNA is transmitted to the next generation in varying proportions under the maternal inheritance mode. This mitochondrial heteroplasmic mouse strain and the improved PCR-RFLP measurement system enable analysis of the transmission of heteroplasmic mitochondrial DNA variants between tissues and generations.