Reversible post-translational modifications represent a mechanism to control tumor metabolism. Here we show that mitochondrial Sirtuin5 (SIRT5), which mediates lysine desuccinylation, ...deglutarylation, and demalonylation, plays a role in colorectal cancer (CRC) glutamine metabolic rewiring. Metabolic profiling identifies that deletion of SIRT5 causes a marked decrease in
C-glutamine incorporation into tricarboxylic-acid (TCA) cycle intermediates and glutamine-derived non-essential amino acids. This reduces the building blocks required for rapid growth. Mechanistically, the direct interaction between SIRT5 and glutamate dehydrogenase 1 (GLUD1) causes deglutarylation and functional activation of GLUD1, a critical regulator of cellular glutaminolysis. Consistently, GLUD1 knockdown diminishes SIRT5-induced proliferation, both in vivo and in vitro. Clinically, overexpression of SIRT5 is significantly correlated with poor prognosis in CRC. Thus, SIRT5 supports the anaplerotic entry of glutamine into the TCA cycle in malignant phenotypes of CRC via activating GLUD1.
Currently, tRNA-derived small RNAs (tsRNAs) are recognized as a novel and potential type of non-coding RNAs (ncRNAs), which participate in various cellular processes and play an essential role in ...cancer progression. However, tsRNAs involvement in colorectal cancer (CRC) progression remains unclear.
Sequencing analyses were performed to explore the tsRNAs with differential expression in CRC. Gain- and loss-of functions of 5'tiRNA-His-GTG were performed in CRC cells and xenograft tumor to discover its role in the progression of CRC. Hypoxia culture and hypoxia inducible factor 1 subunit alpha (HIF1α) inhibitors were performed to uncover the biogenesis of 5'tiRNA-His-GTG. The regulation of 5'tiRNA-His-GTG for large tumor suppressor kinase 2 (LATS2) were identified by luciferase reporter assay, western blot, and rescue experiments.
Here, our study uncovered the profile of tsRNAs in human CRC tissues and confirmed a specific tRNA half, 5'tiRNA-His-GTG, is upregulated in CRC tissues. Then, in vitro and in vivo experiments revealed the oncogenic role of 5'tiRNA-His-GTG in CRC and found that targeting 5'tiRNA-His-GTG can induce cell apoptosis. Mechanistically, the generation of 5'tiRNA-His-GTG seems to be a responsive process of tumor hypoxic microenvironment, and it is regulated via the HIF1α/angiogenin (ANG) axis. Remarkably, LATS2 was found to be an important and major target of 5'tiRNA-His-GTG, which renders 5'tiRNA-His-GTG to "turn off" hippo signaling pathway and finally promotes the expression of pro-proliferation and anti-apoptosis related genes.
In summary, the findings revealed a specific 5'tiRNA-His-GTG-engaged pathway in CRC progression and provided clues to design a novel therapeutic target in CRC.
Aims
To explore the association between cognitive emotion regulation strategies and anxiety and depression among nurses during the COVID‐19 outbreak.
Background
Nurses play a vital role in responding ...to the COVID‐19 outbreak, but many of them suffer from psychological problems due to the excessive workload and stress. Understanding the correlation between cognitive emotion regulation strategies and anxiety and depression will promote targeted psychosocial interventions for these affected nurses.
Methods
This cross‐sectional study of 586 nurses was conducted in Eastern China. Participants completed online questionnaires that investigated anxiety, depression and cognitive emotion regulation strategies.
Results
The prevalence of nurses' anxiety and depression was 27.6% and 32.8%, respectively. Lower self‐blame, rumination and catastrophizing, as well as greater acceptance and positive refocusing, were related to fewer symptoms of anxiety or depression.
Conclusion
The cognitive emotion regulation strategies of acceptance and positive refocusing contribute to reducing anxiety or depression. These strategies should be considered when implementing psychotherapeutic interventions to improve nurses' adverse emotional symptoms.
Implications for Nursing Management
This study highlights the need to assess cognitive emotion regulation strategies use in screening for anxiety and depression. Nurse managers should develop psychosocial interventions including appropriate strategies to help nurses with adverse emotions during a pandemic.
Microcapsules are often used as individually dispersed carriers of active ingredients to prolong their shelf life or to protect premature reactions with substances contained in the surrounding. This ...study goes beyond this application and employs microcapsules as principal building blocks of macroscopic 3D materials with well‐defined granular structures. To achieve this goal and inspired by nature, capsules are fabricated from block‐copolymer surfactants that are functionalized with catechols, a metal‐coordinating motive. These surfactants self‐assemble at the surface of emulsion drops where they are ionically cross‐linked to form viscoelastic capsules that display a low permeability even toward small encapsulants. It is demonstrated that the combination of the mechanical strength, flexibility, and stickiness of the capsules enables their additive manufacturing into macroscopic granular structures. Thereby, they open up new opportunities for 3D printing of soft, self‐healing materials composed of individual compartments that can be functionalized with different types of spatially separated reagents.
Calibrated viscoelastic capsules that enable triggered release of active ingredients, and that can be 3D printed into self‐healing macroscopic granular materials, are introduced. Capsules are produced from catechol‐functionalized surfactants that are ionically cross‐linked at the surface of emulsion drops. The resulting viscoelastic capsules are up‐concentrated to form an ink that is additive manufactured into 3D responsive granular materials.
Selectively Permeable Double Emulsions Ong, Irvine Lian Hao; Amstad, Esther
Small (Weinheim an der Bergstrasse, Germany),
10/2019, Letnik:
15, Številka:
44
Journal Article
Recenzirano
Natural organisms are made of different types of microcompartments, many of which are enclosed by cell membranes. For these organisms to display a proper function, the microcompartments must be ...selectively permeable. For example, cell membranes are typically permeable toward small, uncharged molecules such as water, selected nutrients, and cell signaling molecules, but impermeable toward many larger biomolecules. Here, it is reported for the first time dynamic compartments, namely surfactant‐stabilized double emulsions, that display selective and tunable permeability. Selective permeability is imparted to double emulsions by stabilizing them with catechol‐functionalized surfactants that transport molecules across the oil shell of double emulsions only if they electrostatically or hydrophobically attract encapsulants. These double emulsions are employed as semipermeable picoliter‐sized vessels to controllably perform complexation reactions inside picoliter‐sized aqueous cores. This thus far unmet level of control over the transport of reagents across oil phases opens up new possibilities to use double emulsion drops as dynamic and selectively permeable microcompartments to initiate and maintain chemical and biochemical reactions in picoliter‐sized cell‐mimetic compartments.
Double emulsion drops stabilized with a pH‐responsive surfactant that selectively transports specific molecules across the oil shell are presented. R1 and R2 represent the fluorophilic and hydrophilic groups of the surfactant, respectively.
In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to be important tumor‐associated regulatory factors. LncRNA growth arrest‐specific transcript 5 (Gas5) acts as an anti‐oncogene ...in most cancers. Whether Gas5 acts as an oncogene or anti‐oncogene in hepatocellular carcinoma (HCC) remains unclear. In the present study, the expression and role of Gas5 in HCC were investigated in vitro and in vivo. Lower expression levels of Gas5 were determined in HCC tissues and cells by quantitative reverse transcription‐polymerase chain reaction. Overexpressed Gas 5 lentiviral vectors were constructed to analyze their influence on cell viability, migration, invasion, and apoptosis. Fluorescence in situ hybridization was used to identify the subcellular localization of Gas5. Protein complexes that bound to Gas5 were isolated from HepG2 cells through pull‐down experiments and analyzed by mass spectrometry. A series of novel Gas5‐interacting proteins were identified and bioinformatics analysis was carried out. These included ribosomal proteins, proteins involved in protein folding, sorting, and transportation in the ER, some nucleases and protein enzymes involved in gene transcription, translation, and other proteins with various functions.78 kDa glucose‐regulated protein (GRP78) was identified as a direct target of Gas5 by Rip‐qPCR and Western blot analysis assay. Gas5 inhibited HepG2 cell growth and induced cell apoptosis via upregulating CHOP to activate the ER stress signaling pathway. Further studies indicated that the knockdown of CHOP by shRNA partially reversed Gas5‐mediated apoptosis in HepG2 cells. Magnetic resonance imaging showed that the ectopic expression of Gas5 inhibited the growth of HCC in nude mice. These findings suggest that Gas5 functions as a tumor suppressor and induces apoptosis through activation of ER stress by targeting the CHOP signal pathway in HCC.
Proteases play a pivotal role in regulating important physiological processes from food digestion to blood clotting. They are also important biomarkers for many diseases such as cancers. The ...importance of proteases has led to extensive efforts in the screening of proteases and their inhibitors as potential drug molecules. For example, human immunodeficiency virus (HIV) patients have been treated with HIV-1 protease inhibitors to prolong the life expectancy of patients. Such a close relationship between diseases and proteases provides a strong motivation for developing sensitive, selective, and robust protease assays and sensors, which can be exploited to discover new proteases and inhibitors. In this aspect, protease assays based on levels of proteolytic activities are more relevant than protease affinity assays such as immunoassays. In this review, recent developments of protease activity assays based on different detection principles are discussed and compared. For homogenous assays, fluorescence-based techniques are the most popular due to their high sensitivity and quantitative results. However, homogeneous assays have limited multiplex sensing capabilities. In contrast, heterogeneous assays can be employed to detect multiple proteases simultaneously, given the microarray technology that is already available. Among them, electrochemical methods, surface spectroscopy techniques, and enzyme-linked peptide protease assays are commonly used. Finally, recent developments in liquid crystal (LC)-based protease assays and their applications for detecting proteases and their inhibitors are discussed.
Principles and signal generation mechanisms for both homogenous and heterogeneous proteases assays are reviewed in this article.
Toward hydrogen production from renewable sources, coreforming of dilute bioethanol (5 mol% ethanol) and methane using gliding arc discharge warm plasma is reported. For warm plasma alone, increases ...in methane to ethanol ratio and specific energy input lead to improving hydrogen yield, but low energy efficiency (<60%). The warm plasma coupled with Ni/CeO2/Al2O3 catalyst in a heat‐insulation reactor achieves an energy efficiency of 80%, but the large axial‐temperature drop of the catalyst bed causes low conversions. Therefore, additional heating is provided to maintain the catalyst bed temperature. Under optimal conditions, total carbon conversion of 97% and hydrogen yield of 78% are achieved with an energy cost of 1.16 kWh/Nm3 and energy efficiency of 85%.
Warm plasma catalytic coreforming of dilute bioethanol and methane is reported for hydrogen production from renewable sources using gliding arc discharge and Ni/CeO2/Al2O3 catalyst. Total carbon conversion of 97% and hydrogen yield of 78% are achieved, near thermodynamic equilibrium, with an energy efficiency of 85% and energy cost of 1.16 kWh/Nm3.
In our previous study, we reported that sirtuin5 (SIRT5), a member of the NAD
-dependent class III histone deacetylase family, is highly expressed in colorectal cancer (CRC). Herein we show that ...SIRT5 knockdown impairs the production of ribose-5-phosphate, which is essential for nucleotide synthesis, resulting in continuous and irreparable DNA damage and consequently leading to cell cycle arrest and enhanced apoptosis in CRC cells. These SIRT5 silencing-induced effects can be reversed by nucleoside supplementation. Mechanistically, SIRT5 activates transketolase (TKT), a key enzyme in the non-oxidative pentose phosphate pathway, in a demalonylation-dependent manner. Furthermore, TKT is essential for SIRT5-induced malignant phenotypes of CRC both in vivo and in vitro. Altogether, SIRT5 silencing induces DNA damage in CRC via post-translational modifications and inhibits tumor growth, suggesting that SIRT5 can serve as a promising target for CRC treatment.
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•Warm plasma catalytic steam methane reforming (SMR) for distributed hydrogen production is demonstrated.•The methane conversion of 90% is achieved at total hydrogen (t-H2) production ...rate of 2.7 SLM.•The energy efficiency (of CH4 to t-H2) of 75% and the low energy cost of 1.5 kW h/Nm3 is achieved.•The formation of C2Hx can be suppressed by SEI and S/C at plasma zone, and completely dismissed at catalyst bed zone.
Steam methane reforming (SMR) via thermal catalytic approach is one of the dominant sources of industrial hydrogen, however it proceeds with slow response and low specific productivity. Here we demonstrate a plasma catalytic SMR for distributed hydrogen production, for which warm plasma by gliding arc discharge initiates the reaction, followed by Ni-based catalyst in a heat-insulated reactor without extra heating. In terms of the plasma alone process, specific energy input (SEI), steam/CH4 ratio (S/C) and total inlet flow rate (Ft) contribute to the methane conversion. In parallel, SEI and S/C account for the decrease in C2Hx selectivity hence the increase in selectivity of CO and CO2, while with Ft all the selectivity is approximately constant. The reaction pathway represented by the selectivity can be influenced by SEI and S/C rather Ft. To utilize the heat and active species with the reaction in plasma zone, Ni/CeO2/Al2O3 catalyst bed is coupled. For the coupled process, the conversion approaches the thermodynamic equilibrium values, with the favorable dismissed C2Hx selectivity thus the complete selectivity to CO and CO2. The coupled process was maintained steady for six hours, and the methane conversion of 90% at total hydrogen (t-H2) production rate of 2.7 SLM is achieved under optimum conditions of SEI, S/C, Ft and gas hourly space velocity (GHSV) of 110 kJ/mol, 3, 3 SLM and 18,000 ml·g−1 h−1. Compared to 59% and 2.3 kW h/Nm3 of the plasma alone process, such a coupled process achieves the energy efficiency (of methane to t-H2) of 75% and the low energy cost of 1.5 kW h/Nm3. Consequently, our approach of plasma catalytic SMR features the merits of rapid response, compact system and high specific productivity, which can be anticipated for the emerging needs of distributed hydrogen generation.
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