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Stromal interaction molecule 1 (STIM1) is a single-pass transmembrane endoplasmic/sarcoplasmic reticulum (E/SR) protein recognized for its role in a store operated CaConditional and tamoxifen inducible muscle STIM1 knock-out mouse models were coupled with multi-omics tools and comprehensive physiology to understand the role of STIM1 in regulating SOCE, mitochondrial quality and bioenergetics, and whole-body energy homeostasis.This study shows that STIM1 is abundant in adult skeletal muscle, upregulated by exercise, and is present at SR-mitochondria interfaces. Inducible tissue-specific deletion of STIM1 (iSTIM1 KO) in adult muscle led to diminished lean mass, reduced exercise capacity, and perturbed fuel selection in the settings of energetic stress, without affecting whole-body glucose tolerance. Proteomics and phospho-proteomics analyses of iSTIM1 KO muscles revealed molecular signatures of low-grade E/SR stress and broad activation of processes and signaling networks involved in proteostasis.These results show that STIM1 regulates cellular and mitochondrial Ca

Aggregation-induced emission (AIE) is widely used for fluorescence “on-off-on” detection ions and molecular. Herein, we report a novel AIE chemosensor through self-assembly of quinoline functionalized pillar[5]arene (SPQ5). The SPQ5 can bind with Hg2+ tightly through coordinating reaction. By introducing Hg2+ into AIE-based chemosensor, metal-coordinated chemosensor (SPQ5-Hg2+) was obtained, the SPQ5-Hg2+ could high selectively and sensitively detection of CN− by competitive coordinating interactions. The LODs of SPQ5 for Hg2+ and CN− are 2.53 × 10−8 M and 7.71 × 10−8 M, respectively. In addition, Hg2+ test kit was prepared by loading the SPQ5 chemosensor on a silica gel plate, which could more convenient and efficiency detection Hg2+ and CN−. Interestingly, the chemosensor SPQ5 could instant sense the Hg2+ and CN− by the changing of fluorescence color and fluorescence intensity. Notably, the fluorescence intensity changes of SPQ5 upon the addition of Hg2+ and CN− were utilized as an IMP logic gate at the molecular level, using Hg2+ and CN− as chemical inputs and the fluorescence intensity signal as the output. On the other hand, the test kit by loading SPQ5 on a silica gel plate was prepared for convenient detection of Hg2+. This study provides a practical application for the sensing of toxic ions in aqueous solution by the construction of supramolecular system.

Supramolecular nanostructures (SNSs) have received significant attention in recent years since they endow specific and unique properties to materials. Pillararenes, as a novel group of macrocyclic molecules, present particular features such as ease of modification, more electron-rich cavity as well as captivating host-guest chemistry, thus bestowing them with the abilities to fabricate intriguing SNSs. This feature article highlights the construction methods of pillararene-based supramolecular nanostructures (PSNSs), where most of which are in aqueous media, and the factors that influence the morphological transformation of PSNSs. Moreover, the structure-function relationship of divergent PSNSs is clarified. Finally, the future challenges and perspectives for PSNSs are pointed out and discussed. We hope this review will benefit the researchers interested in engineering PSNSs with on demand morphologies and desired functions.

An azine-containing bispillar[5]arene was designed and synthesized by the reaction of aldehyde functionalized-pillar[5]arene and hydrazine. Then, a novel bispillar[5]arene-based supramolecular pseudopolyrotaxane has been successfully prepared via host-guest interaction. Interestingly, by taking advantage of the host-guest interactions, π-π stacking interactions and hydrogen bonding interactions, the multi-stimuli-responsive gel-sol phase transitions of such a supramolecular pseudopolyrotaxane gel were successfully realized under different stimuli, such as acid, temperature, concentration, and competitive guests. Moreover, this supramolecular system could effectively adsorb dye molecule rhodamine B. It is worth noting that this supramolecular pseudopolyrotaxane gel prepared in cyclohexanol solution (BP5·G·C) could be used as an adsorbent material for adsorbing rhodamine B with adsorption efficiency of 98.4%. Meanwhile, the adsorption efficiency was 97.6% for supramolecular pseudopolyrotaxane gel prepared in DMSO-H2O (v : v, 8 : 2) binary solution (BP5·G·D), also indicating the superior adsorption effect of BP5·G·D toward the dye molecule rhodamine B.

A novel metallosupramolecular polypseudorotaxane has been successfully prepared via a pillar[5]arene-based pseudo[3]rotaxane and zinc ion coordination. The obtained metallosupramolecular polypseudorotaxane could self-assemble to form a fluorescent metallosupramolecular polypseudorotaxane gel at a high concentration. Interestingly, by taking advantage of the dynamic nature of metal–ligand bonds, host–guest interactions and hydrogen bonding interactions, the multiple stimuli-responsive gel–sol phase transitions of such a polypseudorotaxane gel were successfully realized under different stimuli, such as temperature, sulfide, formaldehyde, competitive guests, etc. Moreover, this metallosupramolecular polypseudorotaxane gel could effectively sense Fe3+ and Cu2+via fluorescence. It is worth noting that this metallosupramolecular polypseudorotaxane gel could be used as an ultrasensitive fluorescent sensor for detecting Fe3+ with a fluorescence spectrum detection limit of 0.893 nM. Meanwhile, the detection limit was 45.7 nM for Cu2+, also indicating the superior sensitivity of the gel to Cu2+. Moreover, thin films based on this metallosupramolecular polypseudorotaxane gel were prepared, which could act as convenient test kits for detecting Fe3+ and Cu2+.

A novel sensor (AHP5) comprising a thioacetohydrazone-bridged bispillar[5]arene was developed and shown to fluorescently sense cyanide ions. The sensor manifested a response specific to cyanide over other common anions (SCN−, AcO−, HSO4−, H2PO4−, I−, Br−, ClO4−, Cl−, and F−) in DMSO/H2O (9 : 1, v/v) solution. Upon treatment with cyanide, AHP5 exhibited a significant fluorescence response accompanied by marked changes in its fluorescence spectra. Furthermore, competitive anions had no obvious influence on the probing behavior. Notably, investigation of the recognition mechanism indicated that AHP5 recognized CN− through a deprotonation procedure accompanied by the breaking of intermolecular hydrogen bonds. Furthermore, the sensor was successfully applied to the detection of cyanide in cyanide-containing water samples.

A thioacetohydrazide functionalized pillar[5]arene was synthesized, which could further assemble into a linear supramolecular metal-organic polymer upon adding Zn2+. Furthermore, the obtained linear supramolecular metal-organic polymer could self-assemble to form a fluorescent supramolecular metal-organic gel at high concentration. When TBAOH was added to the viscous solution at high temperature, the obtained solution could not form a supramolecular metal-organic gel upon cooling. More importantly, when Hg2+ ions are added to the metal-organic gel, the strong blue fluorescence is clearly quenched, and this metal-organic gel (xerogel) could effectively remove Hg2+ from water. Simultaneously, a thin film based on the metal-organic gel was prepared, which was confirmed to be a convenient test kit for detecting Hg2+.

Variations in several complement genes are now known to be significant risk factors for the development of age-related macular degeneration (AMD). Despite dramatic effects on disease susceptibility, the underlying mechanisms by which common polymorphisms in complement proteins alter disease risk have remained unclear. Genetically modified mice in which the activity of the complement has been altered are available and can be used to investigate the role of complement in the pathogenesis of AMD. In this mini review, we will discuss some existing complement models of AMD and our efforts to develop and characterize the ocular phenotype in a variety of mice in which complement is either chronically activated or inhibited. A spectrum of complement dysregulation was modeled on the APOE4 AMD mouse model by crossing these mice to complement factor H knockout (cfh-/-) mice to test the impact of excess complement activation, and by crossing them to soluble-complement-receptor-1-related protein y (sCrry) mice, in which sCrry acts as a potent inhibitor of mouse complement acting in a manner similar to CFH. In addition, we have also generated humanized CFH mice expressing normal and risk variants of CFH.

Calcium/calmodulin-dependent protein kinase II (CaM-KII) plays a key role in N-methyl-D-aspartate (NMDA) receptor-dependent long-term synaptic plasticity; its location is critical for signal transduction, and may provide clues that further elucidate its function. We therefore examined the subcellular localization of CaMKII in CA1 stratum radiatum of adult rat hippocampus, by using immuno-electron microscopy after chemical fixation. When tissue was fixed quickly, the concentration of CaMKIIα (assessed by pre-embedding immunogold) was significantly higher in dendritic shafts than in spine heads. However, when tissue was fixed 5 minutes after perfusion with normal saline, the density of labeling decreased in dendritic shaft while increasing in spine heads, implying rapid translocation into the spine during brief perimortem stress. Likewise, in quickly fixed tissue, CaMKII within spine heads was found at comparable concentrations in the “proximal” half (adjacent to the spine neck) and the “distal” half (containing the postsynaptic density [PSD]), whereas after delayed fixation, label density increased in the distal side of the spine head, suggesting that CaMKII within the spine head moves toward the PSD during this interval. To estimate its distribution at the synapse in vivo, we performed postembedding immunogold staining for CaMKII in quick-fixed tissue, and found that the enzyme did not concentrate primarily within the central matrix of the PSD. Instead, labeling density peaked ∼40 nm inside the postsynaptic membrane, at the cytoplasmic fringe of the PSD. Labeling within 25 nm of the postsynaptic membrane concentrated at the lateral edge of the synapse. This lateral “PSD core” pool of CaMKII may play a special role in synaptic plasticity.