The Fenton system in the presence of nitrilotriacetate (NTA) ligand is studied by DFT approach. The calculations show that complexation of Fe(II) with NTA significantly facilitates the H2O2 ...activation. The ferric‐hydroperoxo intermediate NTAFe(III)OOH predominantly decays via the disproportionation into NTAFe(II)OH2 and NTAFe(IV)O involving the formation of a μ‐1,2‐hydroperoxo‐bridged biferric intermediate. In this mechanism, the bridged hydroperoxo is reduced by hydroperoxo ligand rather than by Fe(III). On the one hand, the NTAFe(III)OOH is sluggish to undergo hydrogen ion; on the other hand, it is a good nucleophile that may perform aldehyde deformylation. The present calculations suggest that both ˙OH and Fe(IV)O are generated in the NTA‐assisted Fenton system. However, the polycarboxylate ligand provides a favorable environment for H2O2 to accumulate around iron ion through hydrogen bonding. This promotes the quenching of Fe(IV)O by H2O2, rationalizing why the Fe(IV)O species is hardly detected in the NTA‐assisted Fenton system.
The NTA/Fe/H2O2 Fenton system has been investigated by DFT calculations. The FeIII/FeII recycling is accomplished by the disproportionation of FeIIIOOH into FeIIOH2 and FeIVO via the formation of μ‐1,2‐hydroperoxo‐bridged biferric intermediate. Although both ˙OH and FeIVO are generated, the polycarboxylate environment results in accumulation of H2O2 around iron ion and thus promotes the quenching of FeIVO by H2O2.
Information on flood inundation extent is important for understanding societal exposure, water storage volumes, flood wave attenuation, future flood hazard, and other variables. A number of ...organizations now provide flood inundation maps based on satellite remote sensing. These data products can efficiently and accurately provide the areal extent of a flood event, but do not provide floodwater depth, an important attribute for first responders and damage assessment. Here we present a new methodology and a GIS‐based tool, the Floodwater Depth Estimation Tool (FwDET), for estimating floodwater depth based solely on an inundation map and a digital elevation model (DEM). We compare the FwDET results against water depth maps derived from hydraulic simulation of two flood events, a large‐scale event for which we use medium resolution input layer (10 m) and a small‐scale event for which we use a high‐resolution (LiDAR; 1 m) input. Further testing is performed for two inundation maps with a number of challenging features that include a narrow valley, a large reservoir, and an urban setting. The results show FwDET can accurately calculate floodwater depth for diverse flooding scenarios but also leads to considerable bias in locations where the inundation extent does not align well with the DEM. In these locations, manual adjustment or higher spatial resolution input is required.
PURPOSE
To evaluate the effectiveness on reducing anxiety of a diaphragmatic breathing relaxation (DBR) training program.
DESIGN AND METHODS
This experimental, pre‐test–post‐test randomized ...controlled trial with repeated measures collected data using the Beck Anxiety Inventory and biofeedback tests for skin conductivity, peripheral blood flow, heart rate, and breathing rate.
FINDINGS
The experimental group achieved significant reductions in Beck Anxiety Inventory scores (p < .05), peripheral temperature (p = .026), heart rate (p = .005), and breathing rate (p = .004) over the 8‐week training period. The experimental group further achieved a significant reduction in breathing rate (p < .001).
PRACTICE IMPLICATIONS
The findings provide guidance for providing quality care that effectively reduces the anxiety level of care recipients in clinical and community settings.
A novel and practical fluoroalkyl radical-initiated cascade reaction was developed to access diverse 2-fluoroalkylbenzothiazoles by reacting various fluoroalkyl radical sources, including ...perfluoroalkyl iodide (IC n F2n+1, n = 3–8, 10), ICF(CF3)2, ICF2COOEt, ICF2CF2Cl, or ICF2CF2Br, tetramethylethane-1,2-diamine (TMEDA), and 2-isocyanoaryl thioethers in tetrahydrofuran under nitrogen atmosphere and blue-light irradiation conditions. Furthermore, this one-pot protocol could well be expanded to access various 2-fluoroalkylbenzoselenazoles starting from (2-isocyanophenyl)(methyl)selane, perfluoroalkyl iodides (IC n F2n+1, n = 3–8) or ICF2COOEt and TMEDA.
Display omitted
•Hfq RNA chaperone remodels small RNAs and mRNAs for post-transcriptional regulation.•Single molecule FRET reveals the kinetics of restructuring OxyS small RNA by Hfq.•Restructuring ...requires conserved arginines on the rim of the Hfq hexamer.•Intrinsically disordered regions slow down transitions between OxyS conformations.•Basic and disordered regions of Hfq work together to restructure RNA for regulation.
The Sm protein Hfq chaperones small non-coding RNAs (sRNAs) in bacteria, facilitating sRNA regulation of target mRNAs. Hfq acts in part by remodeling the sRNA and mRNA structures, yet the basis for this remodeling activity is not understood. To understand how Hfq remodels RNA, we used single-molecule Förster resonance energy transfer (smFRET) to monitor conformational changes in OxyS sRNA upon Hfq binding. The results show that E. coli Hfq first compacts OxyS, bringing its 5′ and 3 ends together. Next, Hfq destabilizes an internal stem-loop in OxyS, allowing the RNA to adopt a more open conformation that is stabilized by a conserved arginine on the rim of Hfq. The frequency of transitions between compact and open conformations depend on interactions with Hfqs flexible C-terminal domain (CTD), being more rapid when the CTD is deleted, and slower when OxyS is bound to Caulobacter crescentus Hfq, which has a shorter and more stable CTD than E. coli Hfq. We propose that the CTDs gate transitions between OxyS conformations that are stabilized by interaction with one or more arginines. These results suggest a general model for how basic residues and intrinsically disordered regions of RNA chaperones act together to refold RNA.
Special delivery! An aptamer-directed anticancer drug was molecularly engineered to be delivered to target cells for efficient therapeutic application. The covalent conjugation of drug and aptamer ...creates alternative opportunities for targeted therapy, as multiple yet specific aptamers can be "generated" relatively easily by cell-SELEX for any target cells; this demonstrates the full potential of cell-SELEX as a molecular discovery tool for biomedical studies and drug development.The conjugation of antitumor drugs to targeting reagents such as antibodies is a promising method that can increase the efficacy of chemotherapy and reduce the overall toxicity of the drugs. In this study, we covalently link the antitumor agent doxorubicin (Dox) to the DNA aptamer sgc8c, which was selected by the cell-SELEX method. In doing so, we expected that this sgc8c-Dox conjugate would specifically kill the target CCRF-CEM (T-cell acute lymphoblastic leukemia, T-cell ALL) cells, but with minimal toxicity towards nontarget cells. The results demonstrated that the sgc8c-Dox conjugate possesses many of the properties of the sgc8c aptamer, including high binding affinity (Kd=2.0±0.2 nM) and the capability to be efficiently internalized by target cells. Moreover, due to the specific conjugation method, the acid-labile linkage connecting the sgc8c-Dox conjugate can be cleaved inside the acidic endosomal environment. Cell viability tests demonstrate that the sgc8c-Dox conjugates not only possess potency similar to unconjugated Dox, but also have the required molecular specificity that is lacking in most current targeted drug delivery strategies. Furthermore, we found that nonspecific uptake of membrane-permeable Dox to nontarget cell lines could also be inhibited by linking the drug with the aptamer; thus, the conjugates are selective for cells that express higher amounts of target proteins. Compared to the less effective Dox-immunoconjugates, these sgc8c-Dox conjugates make targeted chemotherapy more feasible with drugs having various potencies. When combined with the large number of recently created DNA aptamers that specifically target a wide variety of cancer cells, this drug-aptoconjugation method will have broad implications for targeted drug delivery.
Flow regimes leading to clogging of pipes exist for most multiphase flows with cohesive particles. Although plugging is critical in many industrial and medical applications, there are few records ...describing the details of the process. To address the problem, we conduct a computed tomography (CT) study of plugging in a cohesive ice slurry. We run experiments for ice concentration of 15%, Re∼3500, particle size 0.2-0.4 mm, and their surface energy ∼150 mJ/m2. The CT scans, combined with experimental logs of the main flow parameters, revealed the formation of deposits around the orifice inserted into the pipe, with a complete blockage formed downflow the orifice. The deposition efficiency of ice was relatively low ∼ 10−3. Reproducing the experimental deposition efficiency with the Lagrangian CFD model, we extracted the probability of particle capture at the orifice, which was about 0.5%. The simulation results illustrated how inter-particle interactions hindered the plugging.
•CT visualization of pipe plugging by cohesive slurry with 15% of particles.•The surface energy of particles was 150 mJ/m2.•Particle deposition efficiency was 0.1% at Re∼3500.•Lagrangian CFD model of the process developed.•Wall capture probability was 0.5%.
The transcription factor MYC is deregulated in almost all human cancers, especially in aggressive lymphomas, through chromosomal translocation, amplification, and transcription hyperactivation. Here, ...we report that high expression of tribbles homologue 3 (TRIB3) positively correlates with elevated MYC expression in lymphoma specimens; TRIB3 deletion attenuates the initiation and progression of MYC-driven lymphoma by reducing MYC expression. Mechanistically, TRIB3 interacts with MYC to suppress E3 ubiquitin ligase UBE3B-mediated MYC ubiquitination and degradation, which enhances MYC transcriptional activity, causing high proliferation and self-renewal of lymphoma cells. Use of a peptide to disturb the TRIB3-MYC interaction together with doxorubicin reduces the tumor burden in Myc
mice and patient-derived xenografts. The pathophysiological relevance of UBE3B, TRIB3 and MYC is further demonstrated in human lymphoma. Our study highlights a key mechanism for controlling MYC expression and a potential therapeutic option for treating lymphomas with high TRIB3-MYC expression.
Parkinson's disease (PD) is a neurodegenerative disease characterized by motor deficits and marked neuroinflammation in various brain regions. The pathophysiology of PD is complex and mounting ...evidence has suggested an association with the dysregulation of microRNAs (miRNAs) and gut dysbiosis. Using a rotenone-induced PD mouse model, we observed that administration of
PS128 (PS128) significantly improved motor deficits in PD-like mice, accompanied by an increased level of dopamine, reduced dopaminergic neuron loss, reduced microglial activation, reduced levels of inflammatory factors, and enhanced expression of neurotrophic factor in the brain. Notably, the inflammation-related expression of miR-155-5p was significantly upregulated in the proximal colon, midbrain, and striatum of PD-like mice. PS128 reduced the level of miR-155-5p, whereas it increased the expression of suppressor of cytokine signaling 1 (SOCS1), a direct target of miR-155-5p and a critical inhibitor of the inflammatory response in the brain. Alteration of the fecal microbiota in PD-like mice was partially restored by PS128 administration. Among them,
,
_6,
, and
were statistically correlated with the improvement of rotenone-induced motor deficits and the expression of miR-155-5p and SOCS1. Our findings suggested that PS128 ameliorates motor deficits and exerts neuroprotective effects by regulating the gut microbiota and miR-155-5p/SOCS1 pathway in rotenone-induced PD-like mice.
Engineered fluorescent protein (FP) chimeras that modulate their fluorescence in response to changes in calcium ion (Ca²⁺) concentration are powerful tools for visualizing intracellular signaling ...activity. However, despite a decade of availability, the palette of single FP-based Ca²⁺ indicators has remained limited to a single green hue. We have expanded this palette by developing blue, improved green, and red intensiometric indicators, as well as an emission ratiometric indicator with an 11,000% ratio change. This series enables improved single-color Ca²⁺ imaging in neurons and transgenic Caenorhabditis elegans. In HeLa cells, Ca²⁺ was imaged in three subcellular compartments, and, in conjunction with a cyan FP—yellow FP—based indicator, Ca²⁺ and adenosine 5′-triphosphate were simultaneously imaged. This palette of indicators paints the way to a colorful new era of Ca²⁺ imaging.
PDF
