Discovery of keratin-degrading enzymes from fungi and bacteria has primarily focused on finding one protease with efficient keratinase activity. Recently, an investigation was conducted of all ...keratinases secreted from a fungus known to grow on keratinaceous materials, such as feather, horn, and hooves. The study demonstrated that a minimum of three keratinases is needed to break down keratin, an endo-acting, an exo-acting, and an oligopeptide-acting keratinase. Further, several studies have documented that disruption of sulfur bridges of the keratin structure acts synergistically with the keratinases to loosen the molecular structure, thus giving the enzymes access to their substrate, the protein structure. With such complexity, it is relevant to compare microbial keratin decomposition with the microbial decomposition of well-studied polymers such as cellulose and chitin. Interestingly, it was recently shown that the specialized enzymes, lytic polysaccharide monoxygenases (LPMOs), shown to be important for breaking the recalcitrance of cellulose and chitin, are also found in keratin-degrading fungi. A holistic view of the complex molecular self-assembling structure of keratin and knowledge about enzymatic and boosting factors needed for keratin breakdown have been used to formulate a hypothesis for mode of action of the LPMOs in keratin decomposition and for a model for degradation of keratin in nature. Testing such hypotheses and models still needs to be done. Even now, the hypothesis can serve as an inspiration for designing industrial processes for keratin decomposition for conversion of unexploited waste streams, chicken feather, and pig bristles into bioaccessible animal feed.
Rheumatoid arthritis (RA) is a systemic poly-articular chronic autoimmune joint disease that mainly damages the hands and feet, which affects 0.5% to 1.0% of the population worldwide. With the ...sustained development of disease-modifying antirheumatic drugs (DMARDs), significant success has been achieved for preventing and relieving disease activity in RA patients. Unfortunately, some patients still show limited response to DMARDs, which puts forward new requirements for special targets and novel therapies. Understanding the pathogenetic roles of the various molecules in RA could facilitate discovery of potential therapeutic targets and approaches. In this review, both existing and emerging targets, including the proteins, small molecular metabolites, and epigenetic regulators related to RA, are discussed, with a focus on the mechanisms that result in inflammation and the development of new drugs for blocking the various modulators in RA.
Exosomes, abundant in blood, deliver various molecules to recipient cells. Endothelial cells are directly exposed to circulating substances. However, how endothelial cells respond to serum exosomes ...(SExos) and the implications in diabetes-associated vasculopathy have never been explored. In the present study, we showed that SExos from diabetic db/db mice (db/db SExos) were taken up by aortic endothelial cells, which severely impaired endothelial function in nondiabetic db/m⁺ mice. The exosomal proteins, rather than RNAs, mostly account for db/db SExos-induced endothelial dysfunction. Comparative proteomics analysis showed significant increase of arginase 1 in db/db SExos. Silence or overexpression of arginase 1 confirmed its essential role in db/db SExos-induced endothelial dysfunction. This study is a demonstration that SExos deliver arginase 1 protein to endothelial cells, representing a cellular mechanism during development of diabetic endothelial dysfunction. The results expand the scope of bloodborne substances that monitor vascular homeostasis.
Current models for inorganic ion transport in porous media describe the adsorption–desorption processes mostly based on empirical adsorption isotherms or simple thermodynamic mechanisms, often ...overlooking the adsorption kinetics. This study introduces a novel unified reactive solute transport model framework that incorporates well-established surface complexation models to describe the adsorption–desorption of ions in the transport process and takes into full consideration the non-equilibrium adsorption, enabling the use of the same set of thermodynamic-kinetic parameters to accurately describe ion transport under different chemical conditions. To evaluate the constructed model, Cr(VI), P(V), and As(V) column transport experiments were carried out using goethite-coated sand as the porous medium. Kinetic constants derived from single-ion transport experiments accurately predicted the cotransport behaviors of Cr(VI), P(V), and As(V) under various flow chemistry conditions, especially the overshooting phenomena of Cr(VI) under P(V) and As(V) competition. The model framework can be easily incorporated into solute transport models with various surface complexation reactions to predict the fate and transport of ions under complexed chemical conditions without extensive parameterization, and thus is a useful complement to the current reactive transport model.
Oxygen vacancies (Ov) as the active sites have significant influences on the gas sensing performance of metal oxides, and self-doping of Ce3+ in CeO2 might promote the formation of oxygen vacancies. ...In this work, hydrothermal process is adopted to fabricate the composites of graphene and CeO2 nanoparticles, and the influences of oxygen vacancies as well as Ce3+ ions on the sensing response to NO2 are studied. It is found that the sensitivity of the composites to NO2 increases gradually, as the proportion of Ce3+ relative to all of the cerium ions is increased from 14.6% to 50.7% but decreases after that value. First-principles calculations illustrate that CeO2 becomes metallic at the Ce3+ proportion of <50.7%, the chemical potential of electrons on surface decreases, and the Fermi level shifts upward due to the existence of low-electronegativity Ce3+ ions, resulting in reduced Schottky barrier height (SBH) at the CeO2/graphene interface, enhanced interfacial charge transfer, and high gas sensing performance. However, deep energy level will be induced at the Ce3+ proportion of >50.7%, and the Fermi level is pinned at the interface. As a result, the density of free electrons is reduced, leading to increased SBH and poor gas sensing response. It demonstrates that an appropriate concentration of oxygen vacancies in CeO2 is needed to enhance the gas sensing performance to NO2.
Glutamate plays an important role in excitotoxicity and ferroptosis. Excitotoxicity occurs through over-stimulation of glutamate receptors, specifically NMDAR, while in the non-receptor-mediated ...pathway, high glutamate concentrations reduce cystine uptake by inhibiting the System Xc-, leading to intracellular glutathione depletion and resulting in ROS accumulation, which contributes to increased lipid peroxidation, mitochondrial damage, and ultimately ferroptosis. Oxidative stress appears to crosstalk between excitotoxicity and ferroptosis, and it is essential to maintain glutamate homeostasis and inhibit oxidative stress responses
. As researchers work to develop natural compounds to further investigate the complex mechanisms and regulatory functions of ferroptosis and excitotoxicity, new avenues will be available for the effective treatment of ischaemic stroke. Therefore, this paper provides a review of the molecular mechanisms and treatment of glutamate-mediated excitotoxicity and ferroptosis.
IPO listing threshold requirements are high, many enterprises have chosen to backdoor listing due to the restrictions of objective factors. In order to study the impact of backdoor listing on ...corporate financial performance, this paper adopts the method of case analysis and takes SF Express, a typical representative of express delivery industry, as an example to analyze whether SF Express has improved its financial performance after backdoor listing by using financial indicators such as debt paying ability, operating ability, profitability and growth ability. The results show that the overall financial performance of SF Express has been improved due to the sufficient capital and the expansion of business scope. The innovation of this paper lies in the horizontal short-term comparison of financial data of SF Express which is backdoor listed and DEPPON Express which is IPO listed in express industry. The research shows that backdoor listing is more conducive to the improvement of the financial performance of enterprises in the short term, providing certain reference value for enterprises that want to go public by backdoor listing in the express industry in the future. However, when deciding to go public, different enterprises should choose suitable listing schemes according to their own financial characteristics and understand the risk and the strategic goal of the enterprise’s own development.
Bismuth vanadate (BiVO
4
) is a promising candidate material for photocatalytic hydrogen generation and photocatalytic degradation of organics. In this paper, first-principle calculations are ...performed to investigate the effects of oxygen vacancy on the structural, elastic, electronic and optical properties of monoclinic BiVO
4
. It is illustrated that oxygen vacancy can exist in BiVO
4
stably and might promote the transition of band gap from indirect to direct ones. Essentially, oxygen vacancy can enhance the hybridization of O2
p
, V3
d
and Bi6
s
orbitals, and shift the band edges. As a result, the dielectric function, refractive index, absorption coefficient, optical reflectivity, loss function and conductivity in the low energy range have a redshift. In addition, the real part of dielectric constant
ɛ
1
, refractive index
n
and reflectivity
R
of ideal BiVO
4
increase with energy in the low energy range; however, they will decrease when oxygen vacancies are generated in BiVO
4
. But the other optical parameters are roughly independent of oxygen vacancies in the whole energy range.
The discovery and identification of biomarkers promote the rational and fast development of medical diagnosis and therapeutics. Clinically, the application of ideal biomarkers still is limited due to ...the suboptimal technology in biomarker discovery. Aptamers are single-stranded deoxyribonucleic acid or ribonucleic acid molecules and can selectively bind to varied targets with high affinity and specificity. Compared with antibody, aptamers have desirable advantages, such as flexible design, easy synthesis and convenient modification with different functional groups. Currently, different aptamer-based technologies have been developed to facilitate biomarker discovery, especially CELL-SELEX and SOMAScan technology. CELL-SELEX technology is mainly used to identify cell membrane surface biomarkers of various cells. SOMAScan technology is an unbiased biomarker detection method that can analyze numerous and even thousands of proteins in complex biological samples at the same time. It has now become a large-scale multi-protein biomarker discovery platform. In this review, we introduce the aptamer-based biomarker discovery technologies, and summarize and highlight the discovered emerging biomarkers recently in several diseases.
Liver steatosis is a common metabolic disorder resulting from imbalanced lipid metabolism, which involves various processes such as de novo lipogenesis, fatty acid uptake, fatty acid oxidation, and ...VLDL secretion. In this study, we discovered that KLF2, a transcription factor, plays a crucial role in regulating lipid metabolism in the liver. Overexpression of KLF2 in the liver of db/db mice, C57BL/6J mice, and Cd36-/- mice fed on a normal diet resulted in increased lipid content in the liver. Additionally, transgenic mice (ALB-Klf2) that overexpressed Klf2 in the liver developed liver steatosis after being fed a normal diet. We found that KLF2 promotes lipogenesis by increasing the expression of SCAP, a chaperone that facilitates the activation of SREBP, the master transcription factor for lipogenic gene expression. Our mechanism studies revealed that KLF2 enhances lipogenesis in the liver by binding to the promoter of SCAP and increasing the expression of genes involved in fatty acid synthesis. Reduction of KLF2 expression led to a decrease in SCAP expression and a reduction in the expression of SREBP1 target genes involved in lipogenesis. Overexpression of KLF2 also increased the activation of SREBP2 and the mRNA levels of its downstream target SOAT1. In C57BL/6J mice fed a high-fat diet, overexpression of Klf2 increased blood VLDL secretion, while reducing its expression decreased blood cholesterol levels. Our study emphasizes the novelty that hepatic KLF2 plays a critical role in regulating lipid metabolism through the KLF2/SCAP/SREBPs pathway, which is essential for hepatic lipogenesis and maintaining blood cholesterol homeostasis.
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