NLRP3 activation and mitosis are mutually exclusive events coordinated by NEK7, a new inflammasome component.

The NLRP3 inflammasome responds to microbes and danger signals by processing and activating proinflammatory cytokines, including interleukin 1ß (IL-1ß) and IL-18. We found here that activation of the NLRP3 inflammasome was restricted to interphase of the cell cycle by NEK7, a serine-threonine kinase previously linked to mitosis. Activation of the NLRP3 inflammasome required NEK7, which bound to the leucine-rich repeat domain of NLRP3 in a kinase-independent manner downstream of the induction of mitochondrial reactive oxygen species (ROS). This interaction was necessary for the formation of a complex containing NLRP3 and the adaptor ASC, oligomerization of ASC and activation of caspase-1. NEK7 promoted the NLRP3-dependent cellular inflammatory response to intraperitoneal challenge with monosodium urate and the development of experimental autoimmune encephalitis in mice. Our findings suggest that NEK7 serves as a cellular switch that enforces mutual exclusivity of the inflammasome response and cell division.

RNPS1 inhibits excessive tumor necrosis factor/tumor necrosis factor receptor signaling to support hematopoiesis in mice.

Null mutations of spliceosome components or cofactors are homozygous lethal in eukaryotes, but viable hypomorphic mutations provide an opportunity to understand the physiological impact of individual splicing proteins. We describe a viable missense allele (F181I) of Rnps1 encoding an essential regulator of splicing and nonsense-mediated decay (NMD), identified in a mouse genetic screen for altered immune cell development. Homozygous mice displayed a stem cell­intrinsic defect in hematopoiesis of all lineages due to excessive apoptosis induced by tumor necrosis factor (TNF)­dependent death signaling. Numerous transcript splice variants containing retained introns and skipped exons were detected at elevated frequencies in Rnps1F181I/F181I splenic CD8+ T cells and hematopoietic stem cells (HSCs), but NMD appeared normal. Strikingly, Tnf knockout rescued all hematopoietic cells to normal or near-normal levels in Rnps1F181I/F181I mice and dramatically reduced intron retention in Rnps1F181I/F181I CD8+ T cells and HSCs. Thus, RNPS1 is necessary for accurate splicing, without which disinhibited TNF signaling triggers hematopoietic cell death.

Green Synthesis of Carbon Quantum dots Derived from Lycium barbarum for Effective Fluorescence Detection of Cr (VI) Sensing.

Green and economical self-doped nitrogen-containing fluorescent carbon quantum dots (N-CQDs) were synthesized using a one-pot hydrothermal treatment method. The optical and structural properties of the N-CQDs were investigated in detail by UV-vis and fluorescence spectroscopy, X-ray diffraction (XRD) techniques, transmission electron microscopy (TEM), and high-resolution transmission electron microscopy (HRTEM). Fourier transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) spectroscopy, and elemental analysis illustrate the surface function and composition of N-CQDs. N-CQDs emit a broad fluorescence between365 Ì´ 465 nm and fluoresce most strongly at the excitation wavelength of 415 nm. Meanwhile, Cr (VI) could significantly burst the fluorescence intensity of N-CQDs. N-CQDs showed an excellent sensitivity and selectivity to Cr (VI), which exhibited good linearity in the range of 0 Ì´ 40 µmol/L with a detection limit of 0.16 µmol/L. In addition, the mechanism of Fluorescence quenching of N-CQDs by Cr (VI) was investigated. This work well provides a research idea for the preparation of green carbon quantum dots from biomass and their use for the detection of metal ions.

The evolution mechanism of an FeMo alloy catalyst for growth of single-walled carbon nanotubes.

Adding small fractions of Mo to Fe nanoparticles (NPs) can reduce the melting point of FeMo NPs to lower than that of Fe NPs to prolong the lifetime of the alloy catalyst which in turn promotes the quality of catalytically synthesized single-walled carbon nanotubes (SWCNTs). In this study, we reveal the mechanism of the above-mentioned abnormal melting behavior by employing molecular dynamics simulations. Our results indicate that the bond length between the Fe atoms and the number of bonds between the Mo atoms play an important role in reducing the melting point of the FeMo NPs. This study provides useful insight into the evolution mechanism of the alloy catalyst for the growth of SWCNTs.

Identification of a candidate therapeutic autophagy-inducing peptide.

The lysosomal degradation pathway of autophagy has a crucial role in defence against infection, neurodegenerative disorders, cancer and ageing. Accordingly, agents that induce autophagy may have broad therapeutic applications. One approach to developing such agents is to exploit autophagy manipulation strategies used by microbial virulence factors. Here we show that a peptide, Tat-beclin 1-derived from a region of the autophagy protein, beclin 1, which binds human immunodeficiency virus (HIV)-1 Nef-is a potent inducer of autophagy, and interacts with a newly identified negative regulator of autophagy, GAPR-1 (also called GLIPR2). Tat-beclin 1 decreases the accumulation of polyglutamine expansion protein aggregates and the replication of several pathogens (including HIV-1) in vitro, and reduces mortality in mice infected with chikungunya or West Nile virus. Thus, through the characterization of a domain of beclin 1 that interacts with HIV-1 Nef, we have developed an autophagy-inducing peptide that has potential efficacy in the treatment of human diseases.

Detection of Triacetone Triperoxide (TATP) Precursors with an Array of Sensors Based on MoS2/RGO Composites.

Triacetone triperoxide (TATP) is a self-made explosive synthesized from the commonly used chemical acetone (C3H6O) and hydrogen peroxide (H2O2). As C3H6O and H2O2 are the precursors of TATP, their detection is very important due to the high risk of the presence of TATP. In order to detect the precursors of TATP effectively, hierarchical molybdenum disulfide/reduced graphene oxide (MoS2/RGO) composites were synthesized by a hydrothermal method, using two-dimensional reduced graphene oxide (RGO) as template. The effects of the ratio of RGO to raw materials for the synthesis of MoS2 on the morphology, structure, and gas sensing properties of the MoS2/RGO composites were studied. It was found that after optimization, the response to 50 ppm of H2O2 vapor was increased from 29.0% to 373.1%, achieving an increase of about 12 times. Meanwhile, all three sensors based on MoS2/RGO composites exhibited excellent anti-interference performance to ozone with strong oxidation. Furthermore, three sensors based on MoS2/RGO composites were fabricated into a simple sensor array, realizing discriminative detection of three target analytes in 14.5 s at room temperature. This work shows that the synergistic effect between two-dimensional RGO and MoS2 provides new possibilities for the development of high performance sensors.

Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis.

Exercise has beneficial effects on human health, including protection against metabolic disorders such as diabetes. However, the cellular mechanisms underlying these effects are incompletely understood. The lysosomal degradation pathway, autophagy, is an intracellular recycling system that functions during basal conditions in organelle and protein quality control. During stress, increased levels of autophagy permit cells to adapt to changing nutritional and energy demands through protein catabolism. Moreover, in animal models, autophagy protects against diseases such as cancer, neurodegenerative disorders, infections, inflammatory diseases, ageing and insulin resistance. Here we show that acute exercise induces autophagy in skeletal and cardiac muscle of fed mice. To investigate the role of exercise-mediated autophagy in vivo, we generated mutant mice that show normal levels of basal autophagy but are deficient in stimulus (exercise- or starvation)-induced autophagy. These mice (termed BCL2 AAA mice) contain knock-in mutations in BCL2 phosphorylation sites (Thr69Ala, Ser70Ala and Ser84Ala) that prevent stimulus-induced disruption of the BCL2-beclin-1 complex and autophagy activation. BCL2 AAA mice show decreased endurance and altered glucose metabolism during acute exercise, as well as impaired chronic exercise-mediated protection against high-fat-diet-induced glucose intolerance. Thus, exercise induces autophagy, BCL2 is a crucial regulator of exercise- (and starvation)-induced autophagy in vivo, and autophagy induction may contribute to the beneficial metabolic effects of exercise.

Real-time resolution of point mutations that cause phenovariance in mice.

With the wide availability of massively parallel sequencing technologies, genetic mapping has become the rate limiting step in mammalian forward genetics. Here we introduce a method for real-time identification of N-ethyl-N-nitrosourea-induced mutations that cause phenotypes in mice. All mutations are identified by whole exome G1 progenitor sequencing and their zygosity is established in G2/G3 mice before phenotypic assessment. Quantitative and qualitative traits, including lethal effects, in single or multiple combined pedigrees are then analyzed with Linkage Analyzer, a software program that detects significant linkage between individual mutations and aberrant phenotypic scores and presents processed data as Manhattan plots. As multiple alleles of genes are acquired through mutagenesis, pooled "superpedigrees" are created to analyze the effects. Our method is distinguished from conventional forward genetic methods because it permits (1) unbiased declaration of mappable phenotypes, including those that are incompletely penetrant (2), automated identification of causative mutations concurrent with phenotypic screening, without the need to outcross mutant mice to another strain and backcross them, and (3) exclusion of genes not involved in phenotypes of interest. We validated our approach and Linkage Analyzer for the identification of 47 mutations in 45 previously known genes causative for adaptive immune phenotypes; our analysis also implicated 474 genes not previously associated with immune function. The method described here permits forward genetic analysis in mice, limited only by the rates of mutant production and screening.

Image-based genome-wide siRNA screen identifies selective autophagy factors.

Selective autophagy involves the recognition and targeting of specific cargo, such as damaged organelles, misfolded proteins, or invading pathogens for lysosomal destruction. Yeast genetic screens have identified proteins required for different forms of selective autophagy, including cytoplasm-to-vacuole targeting, pexophagy and mitophagy, and mammalian genetic screens have identified proteins required for autophagy regulation. However, there have been no systematic approaches to identify molecular determinants of selective autophagy in mammalian cells. Here, to identify mammalian genes required for selective autophagy, we performed a high-content, image-based, genome-wide small interfering RNA screen to detect genes required for the colocalization of Sindbis virus capsid protein with autophagolysosomes. We identified 141 candidate genes required for viral autophagy, which were enriched for cellular pathways related to messenger RNA processing, interferon signalling, vesicle trafficking, cytoskeletal motor function and metabolism. Ninety-six of these genes were also required for Parkin-mediated mitophagy, indicating that common molecular determinants may be involved in autophagic targeting of viral nucleocapsids and autophagic targeting of damaged mitochondria. Murine embryonic fibroblasts lacking one of these gene products, the C2-domain containing protein, SMURF1, are deficient in the autophagosomal targeting of Sindbis and herpes simplex viruses and in the clearance of damaged mitochondria. Moreover, SMURF1-deficient mice accumulate damaged mitochondria in the heart, brain and liver. Thus, our study identifies candidate determinants of selective autophagy, and defines SMURF1 as a newly recognized mediator of both viral autophagy and mitophagy.

High-Performance Trimethylamine Sensor Based on an Imine Covalent Organic Framework.

As trimethylamine (TMA) is widely used in agriculture and industry, inhalation of TMA can cause very serious negative effects on human health. However, most of the current gas sensors for detecting TMA are commonly performed at high temperatures and cannot meet market needs. Inspired by this, we prepared imine covalent organic frameworks (TB-COF) synthesized from two monomers, 1,3,5-tris(4-aminophenyl)benzene (TAPB) and 1,3,5-benzotricarboxaldehyde (BTCA), using acetic acid as a catalyst at room temperature. Based on this, three sensors were prepared for gas sensitivity testing, namely, TA, BT, and TB-COF sensors. The three sensors were tested for 15 different gases at room temperature. From the whole gas sensitivity data, the TB-COF sensor made by compositing TA and BT has a higher sensitivity (6845.9%) to TMA at 500 ppm, which is 6.1 and 5.4 times higher than the response of TA and BT sensors, respectively. The TB-COF sensor adsorbs and desorbs TMA in a controlled 23 s cycle with a low detection limit of 28.6 ppb. This result indicates that TB-COF prepared at room temperature can be used as a gas-sensitive sensing material for real-time monitoring of TMA. The gas sensing results demonstrate the great potential of COFs for sensor development and application and provide ideas for further development of COFs-based gas sensors.

High-Performance Ethylene Glycol Sensor Based on Imine Covalent Organic Frameworks.

The colorless and odorless ethylene glycol is prone to unknowingly causing poisoning, making preventive monitoring of ethylene glycol necessary. In this paper, scandium (III) trifluoromethanesulfonate was used as a catalyst to successfully prepare covalent organic framework (COF) nanospheres linked by imines at room temperature. The COF nanospheres were characterized by XRD, SEM, TEM, FT-IR, UV-Vis and BET. The results show that COF nanospheres have rough surfaces and a large number of mesoporous structures, which greatly increase the active sites on the surface of the sensing material and enhance the gas sensing performance. The sensing results showed that the prepared imine-conjugated COF nanospheres exhibited a good response-recovery ability for 10 consecutive response-recovery cycles for ethylene glycol at room temperature and had a theoretical detection limit of 40 ppb. In addition, the responses of COF nanospheres to nearly 20 interfering gases, including HCl, HNO3, phenol, formaldehyde and aniline, are relatively low compared to the response to ethylene glycol, indicating that the COF nanospheres have high selectivity towards ethylene glycol. The COF nanospheres show good sensitivity and selectivity for the detection of ethylene glycol, which should be attributed to the large specific surface area, hydrogen bonding interactions, and high defects. This work provides an effective method for the detection of ethylene glycol and expands the application field of COF materials.

Synthesis and Sensing Performance of Chitin Fiber/MoS2 Composites.

In this study, chitin fibers (CFs) were combined with molybdenum sulfide (MoS2) to develop high-performance sensors, and chitin carbon materials were innovatively introduced into the application of gas sensing. MoS2/CFs composites were synthesized via a one-step hydrothermal method. The surface properties of the composites were greatly improved, and the fire resistance effect was remarkable compared with that of the chitin monomer. In the gas-sensitive performance test, the overall performance of the MoS2/CFs composite was more than three times better than that of the MoS2 monomer and showed excellent long-term stability, with less than 10% performance degradation in three months. Extending to the field of strain sensing, MoS2/CFs composites can realize real-time signal conversion in tensile and motion performance tests, which can help inspectors make analytical judgments in response to the analysis results. The extensive application of sensing materials in more fields is expected to be further developed. Based on the recycling of waste chitin textile materials, this paper expands the potential applications of chitin materials in the fields of gas monitoring, biomedicine, behavioral discrimination and intelligent monitoring.

Autophagy genes protect against Salmonella typhimurium infection and mediate insulin signaling-regulated pathogen resistance.

A conserved insulin-like pathway modulates both aging and pathogen resistance in Caenorhabditis elegans. However, the specific innate effector functions that mediate this pathogen resistance are largely unknown. Autophagy, a lysosomal degradation pathway, plays a role in controlling intracellular bacterial pathogen infections in cultured cells, but less is known about its role at the organismal level. We examined the effects of autophagy gene inactivation on Salmonella enterica Serovar Typhimurium (Salmonella typhimurium) infection in 2 model organisms, Caenorhabditis elegans and Dictyostelium discoideum. In both organisms, genetic inactivation of the autophagy pathway increases bacterial intracellular replication, decreases animal lifespan, and results in apoptotic-independent death. In C. elegans, genetic knockdown of autophagy genes abrogates pathogen resistance conferred by a loss-of-function mutation, daf-2(e1370), in the insulin-like tyrosine kinase receptor or by over-expression of the DAF-16 FOXO transcription factor. Thus, autophagy genes play an essential role in host defense in vivo against an intracellular bacterial pathogen and mediate pathogen resistance in long-lived mutant nematodes.

Preparation and Gas Sensing Properties of Hair-Based Carbon Sheets.

Waste human hair was carbonized into carbon sheets by a simple carbonization method, which was studied as gas sensing materials for the first time. The effect of carbonization temperature on the structure and gas sensing properties of hair-based carbon sheet was studied by scanning electron microscope, X-ray diffraction, infrared spectrum, Raman spectrum, and gas-sensitive tester. The results showed that the carbonization temperature had a significant effect on the structure and gas sensing performance of carbon sheets, which were doped with K, N, P, and S elements during carbonization. However, the sensor of the carbon sheet does not show good selectivity among six target gases. Fortunately, the carbon sheets prepared at different temperatures have different responses to the target gases. The sensor array constructed by the carbon sheets prepared at different temperatures can realize the discriminative detection of a variety of target gases. For the optimized carbon sheet, the theoretical limit of detection of hydrogen peroxide is 0.83 ppm. This work provides a reference for the resource utilization of waste protein and the development of gas sensors.

Psychological distress and its influencing factors among psychiatric nurses in China: A cross-sectional study.

Background: Psychiatric nurses often face abuse, attacks, escape, suicides, and other situations related to the care of patients with mental disorders, which are more likely to induce psychological distress. Aims: This study aimed to examine the relationship between coping styles and psychological distress among Chinese psychiatric nurses in Shandong and the significance of sleep quality as a mediating factor. Methods: A total of 812 psychiatric nurses in Shandong, China, were investigated using the Psychological Distress Scale (K10), Simplified Coping Style Questionnaire (SCSQ), Pittsburgh Sleep Quality Index (PSQI) and self-compiled general information questionnaire. Results: Psychological distress was detected in 571 psychiatric nurses (70.3%). The psychological distress of psychiatric nurses was significantly different with respect to professional title (χ2 = 10.627, P < 0.05) and shift work (χ2 = 9.120, P < 0.01). Psychological distress positively correlated with negative coping style (r = 0.266, P < 0.01) and sleep quality (PSQIT) (r = 0.532, P < 0.01). A significant positive correlation was found between psychological distress and all dimensions of sleep quality (r = 0.158-0.456, P < 0.05). Professional title, positive coping style, negative coping style, sleep quality (PSQIT), subjective sleep quality, sleep disorder and daytime dysfunction predicted psychological distress in psychiatric nurses (R 2 = 0.363, F = 65.343, P < 0.01). The relationship between negative coping style and psychological distress was partially mediated by sleep quality, with the mediating effect accounting for 37.97% of the total effect. Conclusions: Psychiatric nurses have a high rate of psychological distress, which is closely related to coping styles, and sleep quality has a certain regulatory effect.

Obesity caused by an OVOL2 mutation reveals dual roles of OVOL2 in promoting thermogenesis and limiting white adipogenesis.

Using random germline mutagenesis in mice, we identified a viable hypomorphic allele (boh) of the transcription-factor-encoding gene Ovol2 that resulted in obesity, which initially developed with normal food intake and physical activity but decreased energy expenditure. Fat weight was dramatically increased, while lean weight was reduced in 12-week-old boh homozygous mice, culminating by 24 weeks in massive obesity, hepatosteatosis, insulin resistance, and diabetes. The Ovol2boh/boh genotype augmented obesity in Lepob/ob mice, and pair-feeding failed to normalize obesity in Ovol2boh/boh mice. OVOL2-deficient mice were extremely cold intolerant. OVOL2 is essential for brown/beige adipose tissue-mediated thermogenesis. In white adipose tissues, OVOL2 limited adipogenesis by blocking C/EBPα engagement of its transcriptional targets. Overexpression of OVOL2 in adipocytes of mice fed with a high-fat diet reduced total body and liver fat and improved insulin sensitivity. Our data reveal that OVOL2 plays dual functions in thermogenesis and adipogenesis to maintain energy balance.

Enhanced gas sensing performance of perovskite YFe1-x Mn x O3 by doping manganese ions.

Perovskite YFe1-x Mn x O3 with a hierarchical structure were prepared by a simple hydrothermal method and used as gas sensing materials. The structure, morphology and composition of YFe1-x Mn x O3 were investigated using X-ray diffraction, transmission electron microscopy, scanning electron microscopy and X-ray photoelectron spectroscopy. The gas sensing test showed that all YFe1-x Mn x O3 perovskites with different Mn doping concentrations displayed fast response and recovery characteristics to multiple analytes as well as good stability and recoverability. With the increase of Mn doping concentration, the response of YFe1-x Mn x O3 to four kinds of target atmospheres first increases, then decreases. The sensing performance of YFe1-x Mn x O3 is best when x = 0.05. Compared with pure YFeO3, the responses of YFe0.95Mn0.05O3 to 1000 ppm of CH2O, C2H6O, H2O2 and 100% relative humidity were increased by 835%, 1462%, 812% and 801%, respectively. The theoretical detection limit of YFe0.95Mn0.05O3 for H2O2 and CH2O is 1.75 and 2.55 ppb, respectively. Furthermore, the possibility of buildings a sensor array based on YFe1-x Mn x O3 with different doping concentrations was evaluated by principal component analysis and radar chart analysis. It is feasible to realize the visual and discriminative detection of the target analyte by constructing sensor arrays through radar chart analysis and database construction.

Development and Evaluation of Paclitaxel-Loaded Aerosol Nanocomposite Microparticles and Their Efficacy Against Air-Grown Lung Cancer Tumor Spheroids.

Paclitaxel (as intravenous Taxol) is one of the most applied chemotherapeutics used for the treatment of lung cancer. This project involves the development of a dry powder nanocomposite microparticle (nCmP) aerosol containing PTX-loaded nanoparticles (NP) to be delivered via a dry powder inhaler to the lungs for the treatment of non-small cell lung cancer (NSCLC). Nanoparticles were formulated by a single emulsion and solvent evaporation method, producing smooth, neutral PTX NP of approximately 200 nm in size. PTX nCmP were obtained via spray drying PTX NP with mannitol, producing amorphous wrinkled particles that demonstrated optimal aerosol deposition for in vitro pulmonary delivery. Free PTX, PTX NP, and PTX nCmP were evaluated in vitro in both 2D monolayers and 3D multicellular spheroids (MCS). PTX NP enhanced cytotoxicity when compared to pure drug in the 2D evaluation. However, on a liquid culture 3D tumor spheroid model, PTX NP and pure PTX showed similar efficacy in growth inhibition of MCS. The PTX nCmP formulation had a comparable cytotoxicity impact on MCS compared with free PTX. Finally, PTX nCmP were evaluated in an air-grown 3D MCS platform that mimics the pulmonary environment, representing a new model for the assessment of dry powder formulations.

LMBR1L regulates lymphopoiesis through Wnt/ß-catenin signaling.

Precise control of Wnt signaling is necessary for immune system development. In this study, we detected severely impaired development of all lymphoid lineages in mice, resulting from an N-ethyl-N-nitrosourea-induced mutation in the limb region 1-like gene (Lmbr1l), which encodes a membrane-spanning protein with no previously described function in immunity. The interaction of LMBR1L with glycoprotein 78 (GP78) and ubiquitin-associated domain-containing protein 2 (UBAC2) attenuated Wnt signaling in lymphocytes by preventing the maturation of FZD6 and LRP6 through ubiquitination within the endoplasmic reticulum and by stabilizing "destruction complex" proteins. LMBR1L-deficient T cells exhibited hallmarks of Wnt/ß-catenin activation and underwent apoptotic cell death in response to proliferative stimuli. LMBR1L has an essential function during lymphopoiesis and lymphoid activation, acting as a negative regulator of the Wnt/ß-catenin pathway.

Autophagy gene-dependent clearance of apoptotic cells during embryonic development.

Autophagy is commonly observed in metazoan organisms during programmed cell death (PCD), but its function in dying cells has been unclear. We studied the role of autophagy in embryonic cavitation, the earliest PCD process in mammalian development. Embryoid bodies (EBs) derived from cells lacking the autophagy genes, atg5 or beclin 1, fail to cavitate. This defect is due to persistence of cell corpses, rather than impairment of PCD. Dying cells in autophagy gene null EBs fail to express the "eat-me" signal, phosphatidylserine exposure, and secrete lower levels of the "come-get-me" signal, lysophosphatidylcholine. These defects are associated with low levels of cellular ATP and are reversed by treatment with the metabolic substrate, methylpyruvate. Moreover, mice lacking atg5 display a defect in apoptotic corpse engulfment during embryonic development. We conclude that autophagy contributes to dead-cell clearance during PCD by a mechanism that likely involves the generation of energy-dependent engulfment signals.