Rab26 restricts insulin secretion via sequestering Synaptotagmin-1.

Rab26 is known to regulate multiple membrane trafficking events, but its role in insulin secretion in pancreatic ß cells remains unclear despite it was first identified in the pancreas. In this study, we generated Rab26-/- mice through CRISPR/Cas9 technique. Surprisingly, insulin levels in the blood of the Rab26-/- mice do not decrease upon glucose stimulation but conversely increase. Deficiency of Rab26 promotes insulin secretion, which was independently verified by Rab26 knockdown in pancreatic insulinoma cells. Conversely, overexpression of Rab26 suppresses insulin secretion in both insulinoma cell lines and isolated mouse islets. Islets overexpressing Rab26, upon transplantation, also failed to restore glucose homeostasis in type 1 diabetic mice. Immunofluorescence microscopy revealed that overexpression of Rab26 results in clustering of insulin granules. GST-pulldown experiments reveal that Rab26 interacts with synaptotagmin-1 (Syt1) through directly binding to its C2A domain, which interfering with the interaction between Syt1 and SNAP25, and consequently inhibiting the exocytosis of newcomer insulin granules revealed by TIRF microscopy. Our results suggest that Rab26 serves as a negative regulator of insulin secretion, via suppressing insulin granule fusion with plasma membrane through sequestering Syt1.

Effects of electrode materials on the performance of Zr0.75Hf0.25O2-based ferroelectric thin films via post deposition annealing.

In this work, the effects of top electrode (TE) and bottom electrode (BE) on the ferroelectric properties of zirconia-based Zr0.75Hf0.25O2(ZHO) thin films annealed by post-deposition annealing (PDA) are investigated in detail. Among W/ZHO/BE capacitors (BE = W, Cr or TiN), W/ZHO/W delivered the highest ferroelectric remanent polarization and the best endurance performance, revealing that the BE with a smaller coefficient of thermal expansion (CTE) plays a vital role in enhancing the ferroelectricity of fluorite-structure ZHO. For TE/ZHO/W structures (TE = W, Pt, Ni, TaN or TiN), the stability of TE metals seems to have a larger impact on the performance over their CTE values. This work provides a guideline to modulate and optimize the ferroelectric performance of PDA-treated ZHO-based thin films.

Hafnium-doped zirconia ferroelectric thin films with excellent endurance at high polarization.

Using thermal atomic layer deposition and subsequent rapid thermal annealing without the need for metal clamping atop, a remanent polarization (Pr) of 25.5 µC cm-2 was achieved in a 10 nm-thick ZrO2 film deposited on a W bottom electrode. Hafnium doping was further explored to improve the ferroelectric properties in Pr as well as the endurance of zirconia-based thin films. A significantly enhanced Pr reaching 41 µC cm-2 was obtained for 10 nm-thick hafnium-doped ZrO2 with an optimal Zr : Hf ratio of 3 : 1. Importantly, owing to the greatly reduced leakage, the optimal hafnium-doped ZrO2 thin films exhibited superior retention and outstanding endurance performances at relatively high polarizations, free of serious degradation for up to 2.3 × 109-6.8 × 109 field cycles at an initial Pr of 27 µC cm-2 and were even capable of over 107 cycles at a maximum Pr of 41 µC cm-2. The superb ferroelectricities were demonstrated on big-sized capacitors as well as sub-micrometer ones, isolated or in array. This would empower zirconia-based ferroelectric thin films as a competitive front-runner for practical applications in ferroelectric-related nanoelectronics.

RNA granule-clustered mitochondrial aminoacyl-tRNA synthetases form multiple complexes with the potential to fine-tune tRNA aminoacylation.

Mitochondrial RNA metabolism is suggested to occur in identified compartmentalized foci, i.e. mitochondrial RNA granules (MRGs). Mitochondrial aminoacyl-tRNA synthetases (mito aaRSs) catalyze tRNA charging and are key components in mitochondrial gene expression. Mutations of mito aaRSs are associated with various human disorders. However, the suborganelle distribution, interaction network and regulatory mechanism of mito aaRSs remain largely unknown. Here, we found that all mito aaRSs partly colocalize with MRG, and this colocalization is likely facilitated by tRNA-binding capacity. A fraction of human mitochondrial AlaRS (hmtAlaRS) and hmtSerRS formed a direct complex via interaction between catalytic domains in vivo. Aminoacylation activities of both hmtAlaRS and hmtSerRS were fine-tuned upon complex formation in vitro. We further established a full spectrum of interaction networks via immunoprecipitation and mass spectrometry for all mito aaRSs and discovered interactions between hmtSerRS and hmtAsnRS, between hmtSerRS and hmtTyrRS and between hmtThrRS and hmtArgRS. The activity of hmtTyrRS was also influenced by the presence of hmtSerRS. Notably, hmtSerRS utilized the same catalytic domain in mediating several interactions. Altogether, our results systematically analyzed the suborganelle localization and interaction network of mito aaRSs and discovered several mito aaRS-containing complexes, deepening our understanding of the functional and regulatory mechanisms of mito aaRSs.

Understanding Family Tourism: A Perspective of Bibliometric Review.

The study performed bibliometric visual analyses of family tourism research literature from 2008 to 2021, revealing the knowledge evolution process, research focuses, and future trends in this field. A total of 132 articles on family tourism were collated from the SSCI database of the Web of Sciences core collection and analyzed by CiteSpace. The results show that the number of research studies on family tourism has increased from 2008 to 2021, however, the overall base is small. Purdue University has the highest number of publications and citations. Inter-country cooperation occurs between the United States, China, the United Kingdom, and Australia. Recently, "motivation" and "benefit" have become hot topics in family tourism research, and "social tourism" has received widespread attention, revealing future research directions. Lehto and Wu are the core figures in the family tourism field, and their achievements have been highly cited and peer-recognized. This study focuses on family tourism research in different cultural situations, enriching the knowledge system of family tourism research, and encouraging future family tourism research focus more on seniors and disadvantaged families.

Filamentous GLS1 promotes ROS-induced apoptosis upon glutamine deprivation via insufficient asparagine synthesis.

GLS1 orchestrates glutaminolysis and promotes cell proliferation when glutamine is abundant by regenerating TCA cycle intermediates and supporting redox homeostasis. CB-839, an inhibitor of GLS1, is currently under clinical investigation for a variety of cancer types. Here, we show that GLS1 facilitates apoptosis when glutamine is deprived. Mechanistically, the absence of exogenous glutamine sufficiently reduces glutamate levels to convert dimeric GLS1 to a self-assembled, extremely low-Km filamentous polymer. GLS1 filaments possess an enhanced catalytic activity, which further depletes intracellular glutamine. Functionally, filamentous GLS1-dependent glutamine scarcity leads to inadequate synthesis of asparagine and mitogenome-encoded proteins, resulting in ROS-induced apoptosis that can be rescued by asparagine supplementation. Physiologically, we observed GLS1 filaments in solid tumors and validated the tumor-suppressive role of constitutively active, filamentous GLS1 mutants K320A and S482C in xenograft models. Our results change our understanding of GLS1 in cancer metabolism and suggest the therapeutic potential of promoting GLS1 filament formation.

Mosaic composition of RIP1-RIP3 signalling hub and its role in regulating cell death.

RIP1 and RIP3, cell death mediators, form fibrous amyloids. How RIP1/RIP3 amyloidal oligomers assemble functional necrosomes and control cell death is largely unknown. Here we use super-resolution microscopy to directly visualize cellular necrosomes as mosaics of RIP1 and RIP3 oligomers. The small (initial) mosaic complexes are round, and the large mosaics are in a rod shape. RIP3 oligomers with sizes of tetramer or above are the domains in mosaics that allow MLKL, recruited by phosphorylated RIP3, to oligomerize for necroptosis. Unexpectedly, RIP1 autophosphorylation not only controls the ordered oligomerization of RIP1 but also is required for RIP1-initiated RIP3 homo-oligomerization in correct organization, which is indispensable for the formation of functional rod-shaped mosaics. Similarly, apoptosis initiated by enzymatically defective RIP3 requires the formation of rod-shaped mosaics of RIP3 and RIP1 oligomers. The revealing of nanoscale architecture of necrosomes here innovates our understanding of the structural and organizational basis of this signalling hub in cell death.

Antioxidant effect of yeast on lipid oxidation in salami sausage.

Salami is a kind of fermented meat product with rich nutrition and unique flavor. Because it is rich in fat, it is easy to oxidize to produce bad flavor. Compared with the way of adding artificial or natural antioxidants to reduce the degree of sausage oxidation, the antioxidant characteristics of developing the starter itself deserve more attention. In this study, firstly the antioxidant activities of 5 strains of yeast were measured in vitro, and then the mixture of yeast and Lactobacillus rhamnosus YL-1 was applied to fermented sausage model. The effect of the starter in the sausage model was investigated through physicochemical parameters, degree of fat oxidation, free fatty acid content, and though volatile flavor compound analysis, sensory evaluation and various indexes after storage were observed. Metagenomics was used to explore metabolic pathways, functional genes and key enzymes related to lipid oxidizing substances in sausage in yeast. The results showed that Wickerhamomyces anomalus Y12-3 and Y12-4 had strong tolerance to H2O2, and had higher SOD and CAT enzyme activities. The addition of yeast effectively reduced the material value of peroxidation value and active thiobarbiturate in salami. In flavor analysis, the content of flavor compounds associated with lipid oxidation, such as hexanal, heptanal, nonanal and (E)-2-decenal were significantly lower with the use of Debaryomyces hansenii Y4-1 and Y12-3. Meanwhile, the possible pathways of yeast metabolism of flavor substances related to lipid oxidation (mainly aldehydes) were discussed with the help of metagenomic techniques. According to the results of metagenomics, fatty acid degradation (ko00071) metabolic pathway was related to the degradation of aldehydes through aldehyde dehydrogenase, which was the potential key enzyme.

Degradation of aflatoxin B1 by a recombinant laccase from Trametes sp. C30 expressed in Saccharomyces cerevisiae: A mechanism assessment study in vitro and in vivo.

Aflatoxin B1 (AFB1) is the most harmful mycotoxin and presents risks to human health. Utilization of enzyme to degrade AFB1 is a promising strategy to overcome this problem. In this study, we evaluated the effect of recombinant laccase expressed in Saccharomyces cerevisiae on the degradation of AFB1. It was found that AFB1 could be degraded effectively by laccase up to 91%.The results of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) showed that there were four main degradation products of AFB1 including C16H22O4, C14H16N2O2, C7H12N6O and C24H30O6. Two possible degradation pathways were proposed: 1) AFB1 lost -CO continuously, and then double bonds of furan ring were broken after reactions with H2O, H+, and -NH2; 2) AFB1 occurred decarbonylation reaction after losing -CO and double bonds were broken by additional reaction with H+. Two toxicological activity sites in AFB1, including a double bond of furo-furan ring and lactone ring in the coumarin in moiety, were destroyed. The toxicity of AFB1 degradation products was evaluated on HepG2 cells and in vivo tests, and the results indicated a decrease in hepatocytes apoptosis, liver and kidney histopathological lesions, oxidative stress, and inflammation as compared to non-laccase degraded AFB1. Moreover, the AFB1 degradation products significantly decreased the cytotoxicity and hepatotoxicity. This investigation provides innovative evidence on the effectiveness of laccase expressed in Saccharomyces cerevisiae in detoxifying AFB1.

Open-ended W18O49-filled tungsten dichalcogenide nanotubes grown on a W substrate to efficiently catalyze hydrogen evolution.

A scalable infrared-heating CVD method was developed to grow few-walled WSe2 or WS2 nanotube arrays in situ filled with highly conductive single-crystal W18O49, and a simple pressure control led to their universally uncapped top-ends. Open-ended WS2 nanotubes grown on the W substrate performed excellently as an electrocatalyst to facilitate the HER in acid, contributing to high-density active edge sites and good electronic coupling between the substrate and nanotubes.

Synthesis and magnetic properties in quaternary Ca1-x Pr x Co2As2 single crystals.

Series of Ca1-x Pr x Co2As2 (x = 0, 0.10, 0.25, 0.4, 0.6, 0.75, 0.85, 1) single crystals have been synthesized in order to clarify the variation of magnetic order from antiferromagnetic (AFM) in CaCo2As2 to ferromagnetic (FM) in PrCo2As2. It is found that the lattice constant of c-axis are contracted with the introduction of Pr into Ca sites in CaCo2As2. Electronic transport measurements reveal the metallicity in this system. Systematic magnetic measurements and analysis show that substituting only 10% of Pr for Ca changes the magnetic ground state from A-type AFM ordering of Co magnetic moment in CaCo2As2 to FM ordering in Ca1-x Pr x Co2As2 (0.1 ⩽ x ⩽ 1). Most importantly, the abrupt drop of low temperature magnetic susceptibility below T FiM with x ⩾ 0.25 and the observed magnetic pole reversal with x ⩾ 0.4 suggests an AFM coupling between Co 3d and Pr 4f magnetic sublattice. Finally, a detailed magnetic phase diagram in this system has been obtained.

Sex Hormones Enhance Gingival Inflammation without Affecting IL-1ß and TNF-α in Periodontally Healthy Women during Pregnancy.

Hormones (progesterone and estradiol) change greatly during pregnancy; however, the mechanism of hormonal changes on gingival inflammation is still unclear. This study is to evaluate the effects of hormonal changes during pregnancy on gingival inflammation and interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in gingival crevicular fluid (GCF). 30 periodontally healthy pregnant women were evaluated in the first, second, and third trimesters. 20 periodontally healthy nonpregnant women were evaluated twice (once per subsequent month). Clinical parameters including probing pocket depth (PPD), bleeding index (BI), gingival index (GI), clinical attachment level (CAL), and plaque index (PLI) were recorded. GCF levels of IL-1ß and TNF-α and serum levels of progesterone and estradiol were measured. From the data, despite low PLI, BI and GI increased significantly during pregnancy; however, no significant changes in PLI, CAL, IL-1ß, or TNF-α GCF levels were observed. Although IL-1ß, not TNF-α, was higher in pregnant group than in nonpregnant group, they showed no correlation with serum hormone levels during pregnancy. GI and BI showed significant positive correlation with serum hormone levels during pregnancy. This study suggests that sex hormone increase during pregnancy might have an effect on inflammatory status of gingiva, independent of IL-1ß and TNF-α in GCF.