Knockout of the Muscle-Specific E3 Ligase MuRF1 Affects Liver Lipid Metabolism upon Dexamethasone Treatment in Mice
In order to preserve muscle mass during catabolic states, investigators are actively searching for a specific inhibitor of MuRF1, the only known E3 ligase that can target muscle contractile proteins for their degradation. However, what would be the consequences of such inhibitors on other organs, both in the short and long term? Indeed, skeletal muscles can provide amino acids for liver gluconeogenesis, which is a crucial adaptation for maintaining glucose homeostasis upon elevated energy demands (e.g., during prolonged starvation). Comparing 3-month-old wild-type and MuRF1-KO mice, we measured tissue weights, liver glycogen, lipid and protein content, and liver biochemical composition using Fourier transform infrared (FTIR) spectrometry in control animals and in dexamethasone (Dex)-treated animals. Dex induces a catabolic situation with muscle atrophy and lipid deposits in the liver. In response to Dex treatment, liver glycogen, lipid, and protein content increased in wild type (WT) and MuRF1-KO mice. We found that MuRF1 deletion differentially affected organ weights, the liver of KO mice being hypertrophied upon Dex treatment when compared to WT mice. Upon Dex treatment, muscle mass was preserved in MuRF1-KO mice, and by contrast, liver lipid content increased more in these animals than in WT mice. PLS-DA analysis of FTIR showed that the levels of 13 markers were significantly altered in KO vs WT mice, witnessing profound alterations of lipid, protein, and glycogen content in the liver due to the absence of MuRF1. Using Nile red and oil red lipid staining, we also found that both membrane-linked lipids and intracellular lipid droplets were altered due to the absence of MuRF1. Altogether, it seems that when the liver is deprived of the possibility of obtaining amino acids from muscle upon Dex treatment, there is a concomitant increase in tissue weight and anabolic activity.
Off-On Photo- and Redox-Triggered Anion Transport Using an Indole-Based Hydrogen Bond Switch
A stimulus-responsive indole-based hydrogen bonding switch is reported, which enables off-on activation of transmembrane ion transport in response to photo- and redox triggers. This is achieved by alkylation of an indole-based anionophore, preorganized through intramolecular hydrogen bonding, with -nitrobenzyl and azobenzene cages. This renders the anionophore inactive through formation of a six-membered intramolecular hydrogen bonding interaction and locking of the anion binding protons. Decaging with biologically relevant light and redox stimuli leads to efficient activation of anion transport across lipid bilayer membranes by unlocking the hydrogen bond donors, such that they are now available for anion binding and transport.
Treating Waste with Waste: Activated Bauxite Residue (ABR) as a Potential Wastewater Treatment
Bauxite residue (or red mud) is a highly alkaline waste generated during the extraction of alumina. As a result of the substantial accumulation of bauxite residue in tailings facilities, there is a growing interest in exploring the potential for reusing this material for other purposes. The main objective of this study is to evaluate the use of activated bauxite residue (ABR) for remediating oil sands process-affected water (OSPW) and as a supplement to municipal wastewater treatment through bench-scale, proof-of-concept studies. The ABR is produced through a reduction roasting process that alters the physicochemical properties of bauxite residue, resulting in the generation of potentially effective adsorbent media. The treatment performance via chemical and biological activity removals (cytotoxicity, estrogenicity, and mutagenicity) was also assessed. For OSPW, ABR treatment resulted in the effective removal of recalcitrant acid-extractable organics (AEOs), with kinetics following the pseudo-second-order and comparable adsorption capacity to other waste materials (e.g., petroleum coke). ABR also effectively reduced the estrogenicity and mutagenicity of OSPW, albeit cytotoxicity increased at higher dosages, possibly due to some components leaching out of the material (e.g., metals). For municipal wastewater, ABR treatment reduced fecal coliform concentrations (>99%), total phosphorus (up to 98%), total ammonia-nitrogen (63%), estrogenicity (nondetectable), and mutagenicity (nondetectable), especially in the primary effluent. The ultimate end use of ABR is for the recovery of valuable metals (especially iron) and as a construction material, but additional work is needed to optimize the dosage (currently in the g/L range) and maximize the use of ABR as an adsorbent prior to its subsequent uses.
One-Pot Stereospecific Synthesis of 1,4-Oligosaccharides by Glycal-Derived Vinyl Epoxides Assembly
Recently, naturally occurring linear 1,4-glycans have attracted remarkable attention for their activity in cancer and neurodegenerative disease treatment. Classical chemical synthetic strategies for linear 1,4-oligosaccharides are considerably time-consuming due to orthogonal protection/deprotection, the introduction of leaving groups, and various forms of activation of the glycosylation reaction. Herein, we present a new one-pot microwave-activated reiterative assembly of glycal-derived vinyl epoxides in an uncatalyzed substrate-dependent stereospecific process for the preparation of both β-1,4-d-Gulo and α-1,4-d-Manno oligosaccharides.
Discovery of Five Classes of Bacterial Defensins: Ancestral Precursors of Defensins from Eukarya?
Defensins are present in many organisms and are divided into two evolutionary groups, termed - and -defensins. -defensins have only recently been reported in bacteria, and knowledge of these defensins is limited, with no family classification. Here, we describe the identification of 74 -defensins from bacteria and propose five classes for their classification. We also report the first NMR structure determination of a defensin, as well as its in silico expression analysis. Xanthusin-1 has a unique structure among the published defensins, which could indicate that the proposed class II peptides constitute a separate group of defensins. Xanthusin-1 gene expression was observed in casitone-based and coculture-grown media. Our results demonstrate a wider distribution of defensins outside the Eukarya domain, shedding light on the origin and distribution of defensins. The sharing of three disulfide defensins between bacteria and eukaryotes points to a possible prokaryotic origin of the CSαβ motif. Moreover, the identification of defensins in Gram-positive and Gram-negative bacteria indicates an early origin but with many gene losses during the evolutionary process, similar to findings for eukaryotic defensins.
Correction to "Phytochemical Composition, Antioxidant, Antimicrobial, Antibiofilm, and Antiquorum Sensing Potential of Methanol Extract and Essential Oil from Delile (Acanthaceae)"
[This corrects the article DOI: 10.1021/acsomega.3c06246.].
Electrochemical Formation of Pb Microwires with Tunable Morphology on Liquid Metal Electrodes
Liquid metal electrodes based on Ga are an emerging area of interest given their fluid properties which can have significant impact on electrochemical processes. Here we study metal electrodeposition, namely lead electrodeposition on the liquid metal electrodes, gallium (Ga) and galinstan (GaInSn), which was performed in two different Pb electrolytes (PbCl and Pb(NO)) to investigate any differences in the nature of the electrodeposit. Cyclic voltammetry and chronoamperometry were used to study the characteristics, kinetics, and nucleation and growth mechanisms of the electrodeposition process. Analysis of this electrochemical data, such as current density-time transients and diffusion coefficients under different potentials, revealed distinct behaviors for Pb deposition at each liquid metal and electrolyte, influencing the final morphology of the lead deposit. It was also found that the electrolyte concentration and deposition time were found to impact the morphology of the electrodeposited Pb. Scanning electron microscopy and energy dispersive X-ray spectroscopy revealed various types of Pb microstructures, including wire, branch-like, and flake-like formations, highlighting the differences in lead structural development when deposited on liquid gallium and Galinstan electrodes.
Dyed Hair and Swimming Pools: The Influence of Chlorinated and Nonchlorinated Agitated Water on Surface-Enhanced Raman Spectroscopic Analysis of Artificial Dyes on Hair
Chlorine, commonly found in pools and tap water, presents an intriguing concern in forensic hair analysis due to its sources and composition. Current forensic analysis involves optical microscopy which is subjected to advanced training where even multiple experts can deliver opposing conclusions for the same hair sample. Despite challenges in traditional analysis methods, emerging techniques like surface-enhanced Raman spectroscopy (SERS) offer promising solutions, showcasing success even in harsh environments like prolonged sunlight or stagnant water immersion. This study employs partial least-squares discriminant analysis (PLS-DA) to evaluate SERS efficacy in identifying dyes on hair immersed in chlorinated and distilled moving water for up to eight weeks. Our results demonstrated that one semipermanent colorant overwhelmingly influenced Raman signals in dyed hair exposed to both chlorinated and nonchlorinated water over an eight-week period, masking other colorants' spectral signatures. Despite one colorant's dominance, PLS-DA identified underlying colorants and their exposure conditions, suggesting persistent, unique interactions between original colorants and the environment. This study demonstrates the high potential for PLS-DA-based identifications of dyes on hair using SERS.
Influence of Microwave-Assisted Supercritical Carbon Dioxide Treatment on the Pore Structure of Low-Rank Coal
CO injection into coal seams not only enhances coalbed methane (CBM) extraction but also allows for CO sequestration. Microwave irradiation is considered to be an effective technology to enhance CBM extraction. In this paper, the effects of microwave irradiation and supercritical CO immersion on the pore structure of low-rank coals were investigated by scanning electron microscopy (SEM), mercury-in-pressure (MIP), low-temperature nitrogen adsorption (LTNGA), and carbon dioxide isothermal adsorption/desorption (COIA/D) of coal samples. The results showed that the macropores and micropores of the coal samples were more developed after microwave irradiation. After carbon dioxide immersion, the coal samples showed huge fissures, and the meso- and micropores were reduced. In contrast, microwave-assisted carbon dioxide not only reduced the specific surface area in the meso- and microporous stages and decreased the adsorption sites of methane but also enhanced the pore connectivity in the macroporous stage instead of the appearance of huge fissures. This study illustrates the potential of microwave-assisted supercritical carbon dioxide for enhanced coalbed methane extraction and carbon dioxide sequestration.
Promising Proteolysis-Targeting Chimera for Mutant p53-R175H
The tumor suppressor protein p53 is among the most commonly mutated proteins across a variety of cancer types. Notably, the p53 R175H mutation ranks as one of the most prevalent hotspot mutations. Proteolysis-targeting chimeras (PROTACs) represent a class of bifunctional molecules capable of harnessing the cellular ubiquitin-proteasome pathway to facilitate targeted protein degradation. Despite the potential of PROTACs, limited research has been directed toward the degradation of the p53-R175H mutant protein. In this study, we developed a series of peptide-based PROTACs, leveraging known peptide ligands for both the p53-R175H mutation and the E3 ubiquitin ligase VHL. Our findings indicate that one of these peptide-based PROTACs is capable of directing the p53-R175H protein to the proteasome for degradation within a recombinant expression system. Moreover, by synthesizing a fusion peptide PROTAC molecule that incorporates a membrane-penetrating peptide, we have demonstrated its ability to traverse cellular membranes and subsequently reduce the levels of the p53-R175H mutant protein. Importantly, the degradation of p53-R175H was found to mitigate the cellular migration and invasion. In summary, our study introduces a novel class of protein degraders and establishes a foundational framework for the therapeutic management of cancers associated with p53 mutations.
One-Pot Synthesis of -Fused Quinolone-4 Tetracyclic Scaffolds from 2,2-Disubstituted Indolin-3-ones
A cascade transformation of C2-quaternary indoxyls leading to an efficient assembly of complex (dihydro)indolo[1,2-]quinolin-5-one ring systems is reported. The method involves the gram-scale preparation of 2-(2-aryl-3-oxoindolin-2-yl)-2-phenylacetonitriles which are then converted with methyl ketones to the corresponding 2-(2-oxo-2-aryl(alkyl)ethyl)-2-phenylindolin-3-ones. The latter can either be isolated with good yields (75-96%) or, in the case of -nitroacetophenone, used for further base-assisted intramolecular SAr cyclization resulting in indoxyl-fused quinolone-4 hybrids (up to 95%).
Identification of the Active EPA/AA-Binding Ether-Type Phosphatidylcholine Derived from the Starfish for C2C12 Myotube Growth
Concerns about nutritional approaches for promoting skeletal muscle mass and function have increased. This study assessed the effects of starfish-derived glycerophospholipids (PLs) (SPL), characterized by unique ether-linked subclasses, alkylacyl (Alk)- and alkenylacyl (Pls)-PL, on skeletal muscle function, focusing on myotube formation in C2C12 myoblasts. SPL was prepared via chloroform/methanol extraction from , followed by silica gel chromatography fractionation. Myoblasts were induced to differentiate with or without SPL treatment. On day 7 of differentiation, 50 μg/mL of SPL treatment increased myotube diameter. The phosphatidylcholine (PC) fraction (SPC) also enhanced myotube growth at 30 μg/mL. LC-MS/MS analysis indicated the most abundant PC molecular species in SPC were Alk- and Pls-PC with eicosapentaenoic acid and arachidonic acid. Treatment with 1--hexadecyl-2-arachidonoyl-PC, 1-1()-hexadecenyl-2-arachidonoyl-PC or 1--hexadecyl-2-eicosapentaenoyl-PC increased myotube diameter and myokine Il-15 mRNA expression. These results demonstrate a novel functionality of SPC and highlight the role of ether-type PC molecules in muscle function.
Conception and Optimization of Extraction-Free Loop-Mediated Isothermal Amplification Detection of Dry Rot Fungus
The use of nucleic acid-based detection tools for microorganisms and fungi has become a gold standard. This is particularly the case for wood-decaying fungi like which are hard to discriminate based on macroscopic and microscopic observations. This dry rot is important to detect as it is particularly destructive in an infested building, which requires immediate action to prevent spreading and significant damage to structural elements. Through the development and optimization of loop-mediated isothermal amplification against -specific rDNA internal transcribed spacer region, we demonstrate that it is possible to achieve rapid and specific amplification without nonspecific self-amplification in a similar range as real-time quantitative PCR without any necessary DNA isolation using a colorimetric detection assay. Through a combined set of self-amplification minimization along with hand-held sample homogenization, the LAMP assay was optimized to provide a femtogram-range assay capable of confirming identification in a real field sample either predominantly composed of or containing the fungus while remaining negative when tested on different types of fungi found in basement-collected samples.
Enzyme Benchmarking with Polyethylene Furanoate Soluble Scaffolds for Directed Evolution of PEFases
Plastic waste is a major threat in our industrialized world and is driving research into bioplastics. The success of biobased polyethylene furanoate (PEF) as a viable alternative to polyethylene terephthalate (PET) of fossil origin will depend on designing effective enzymes to break it down, aiding its recycling. Here, a panel of fungal and bacterial cutinases were functionally expressed in a tandem yeast expression system based on and . The activity of the enzyme panel was tested with soluble PEF model scaffolds, observing a correlation with the degradation of real PEF powder. A high-throughput colorimetric screening assay based on the PEF scaffold diethyl furan-2,5-dicarboxylate was developed, establishing the basis for future directed evolution campaigns of PEFases.
Inflammation-Modulating Biomedical Interventions for Diabetic Wound Healing: An Overview of Preclinical and Clinical Studies
A diabetic wound exemplifies the challenge of chronic, nonhealing wounds. Elevated blood sugar levels in diabetes profoundly disrupt macrophage function, impairing crucial activities such as phagocytosis, immune response, cell migration, and blood vessel formation, all essential for effective wound healing. Moreover, the persistent presence of pro-inflammatory cytokines and reactive oxygen species, coupled with a decrease in anti-inflammatory factors, exacerbates the delay in wound healing associated with diabetes. This review emphasizes the dysfunctional inflammatory responses underlying diabetic wounds and explores preclinical studies of inflammation-modulating bioactives and biomaterials that show promise in expediting diabetic wound healing. Additionally, this review provides an overview of selected clinical studies employing biomaterials and bioactive molecules, shedding light on the gap between extensive preclinical research and limited clinical studies in this field.
Study of Hydrolysis Kinetics and Synthesis of Single Isomer of Phosphoramidate ProTide-Acyclovir
Acyclovir (ACV) is a vital treatment for herpes simplex (HSV) and varicella-zoster virus (VZV) infections that inhibit viral DNA polymerase. Phosphoramidate ProTides-ACV, a promising technology, circumvents the reliance on thymidine kinase (TK) for activation. Twelve novel single isomers of phosphoramidate ProTide-ACV were synthesized. Successful isomer separation was achieved, emphasizing the importance of single isomers in medical advancements. The enzymatic hydrolysis kinetics of the synthesized compounds were investigated by using carboxypeptidase Y (CPY). The results revealed a faster conversion for the isomer p- than for the p-diastereomer. Hydrolysis experiments confirmed steric hindrance effects, particularly with the -butyl and isopropyl groups. Molecular modeling elucidated the mechanisms of hydrolysis, supporting the results of the experiments. This research sheds light on the potential of phosphoramidate ProTides-ACV, bridging the gap in understanding their biological and metabolic properties, while supporting future investigations into anti-HSV activity. Preliminary screening revealed that three of the four single isomers demonstrated superior antiviral efficacy against wild-type HSV-1 compared to acyclovir, with isomer ultimately reducing the viral yield at 200 μM. These findings emphasize the importance of isolating racemic ACV-ProTides as pure single isomers for future drug development.
Dye-Decolorizing Peroxidases Maintain High Stability and Turnover on Kraft Lignin and Lignocellulose Substrates
Fungal enzyme systems for the degradation of plant cell wall lignin, consisting of, among others, laccases and lignin-active peroxidases, are well characterized. Additionally, fungi and bacteria contain dye-decolorizing peroxidases (DyP), which are also capable of oxidizing and modifying lignin constituents. Studying DyP activity on lignocellulose poses challenges due to the heterogeneity of the substrate and the lack of continuous kinetic methods. In this study, we report the kinetic parameters of bacterial DyP from 75iv2 and fungal DyP from on insoluble plant materials and kraft lignin by monitoring the depletion of the cosubstrate of the peroxidases with a HO sensor. In the reactions with spruce, both enzymes showed similar kinetics. On kraft lignin, the catalytic rate of bacterial DyP reached 30 ± 2 s, whereas fungal DyP was nearly 3 times more active (81 ± 7 s). Importantly, the real-time measurement of HO allowed the assessment of continuous activity for both enzymes, revealing a previously unreported exceptionally high stability under turnover conditions. Bacterial DyP performed 24,000 turnovers of HO, whereas the fungal DyP achieved 94,000 HO turnovers in 1 h with a remaining activity of 40 and 80%, respectively. Using mass spectrometry, the depletion of the cosubstrate HO was shown to correlate with product formation, validating the amperometric method.
Ignition Delay Time Measurements of Substituted Phenol Additives in a Toluene Reference Fuel
Using a rapid compression machine, fuel autoignition resistance can be quantified by the ignition delay time measurements of homogeneous mixtures. As the occurrence and intensity of knock in spark ignition engines are related to autoignition resistance, ignition delay time measurements give valuable insight into fundamental fuel combustion properties that can be used to predict undesirable combustion behavior. Therefore, the work presented in this paper aims to understand the autoignition resistance of a gasoline surrogate fuel and how it is affected by the addition of substituted phenol additives from ignition delay time measurements in a rapid compression machine. Six substituted phenols were tested: -cresol, 2,4-xylenol, 2,5-xylenol, 2,6-xylenol, 3,4-xylenol, and 3,5-xylenol. Lean and stoichiometric mixtures, as well as stoichiometric mixtures with N dilution, were studied at engine-relevant conditions of 20 bar between 700 and 950 K. It was found that most additives were able to lengthen the base fuel ignition delay time at high and low temperatures, but that the most effective had two methyl groups located adjacent to each other.
Kombucha-Proteinoid Crystal Bioelectric Circuits
We propose "kombucha-proteinoid crystal bioelectric circuits" as a sustainable bio-computing platform. These circuits are hybrid biological-inorganic devices that utilize crystal growth dynamics as the physical substrate to convert information. Microfluidic prototypes couple custom-synthesized thermal proteinoids within kombucha cellulose matrices and metastable calcium carbonate solutions. This bio-mineral configuration examines if precision modulation of crystal growth rates could instantiate reconfigurable logic gates for unconventional computing applications. Programming organic acid secretions allows for the adjustment of biotic-mineral polarity, thereby establishing microbial-synthetic pairings that consistently regulate the crystal growth rate of calcite deposition. By coordinating intrinsic physicochemical phenomena, accrued mineral densities literally crystallize additive/multiplicative operations via Boolean AND/OR logics. An additional way to generate structured logics similar of neural assemblies is by chaining modular crystallizer units. Proteinoid-guided carbonate crystallization may prove to be a viable material platform for unconventional computing-green, self-organizing, scalable architectures grown directly from solution-pending definitive affirmation of proof-of-concept.
Experimental Study on the Effect of HO Concentration on the Degradation of Sulfur Hexafluoride by Two-Stage Tandem DBD
SF is a greenhouse gas widely used in the power industry that cannot be directly emitted. This study employs a self-designed two-stage dielectric barrier discharge (DBD) plasma series method that was used to degrade SF gas and analyzes the effect of HO concentration. The results indicate that the SF degradation rate (DR) initially increased and then decreased with the rise in the water vapor content. When the added HO concentration increased from 0.5 to 1.5%, the degradation rate of SF increased from 89.49 to 100%, achieving complete degradation of SF. However, when the HO concentration further increases to 2.5%, the degradation rate of SF decreased to 92.83%. The energy efficiency of SF degradation in the primary reaction system first increased and then decreased with the increase of HO concentration, while that of SF in the secondary reaction system first decreased and then increased. It was found that the products of SF were SOF, SO, SOF, and SOF. The addition of HO increased the selectivity of SO in the decomposition products to 75.17%, and inhibit the formation of SOF and SOF. This study provides experimental support for the degradation of SF waste gas and provides a research direction for its industrial application.
Aluminum Dust Explosion Suppression Performance and Mechanism of a New Mesoporous Composite Explosion Suppressant
In this paper, using a 20 L spherical explosive device and a Hartmann device, we carried out explosion suppression experiments on 19 and 30 μm aluminum powders (500 g/m) with different concentrations of the new explosive suppressants (MCM41@CS-APP) and CaCO and elaborated on the suppression mechanism of the explosion of MCM41@CS-APP on aluminum powder. The experimental results show that when the concentration of the explosion suppressor is 50 g/m, the maximum explosion pressure ( ) produced by the explosion of mixed dust is higher than that of the explosion of aluminum powder, and with the increase of the concentration of the deflagration suppressant, the of the mixed dust decreases. When the concentrations of MCM41@CS-APP and CaCO reached 400 g/m, the of the mixed dust (Al = 19 μm) was 0.133 and 0.364 MPa, which decreased by 81.3% and 48.9%, respectively. The of the mixed dust (Al = 30 μm) was not significant. Both detonation inhibitors inhibited the explosion of aluminum powder; the detonation duration of Al/MCM41@CS-APP is shorter; there are fewer aluminum particles in the product; and the initial oxidation temperature of aluminum powder is higher.