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β-lactamases inactivate β-lactam antibiotics leading to drug resistance. Consequently, inhibitors of β-lactamases can combat this resistance, and the β-lactamase inhibitory protein (BLIP) is a naturally occurring inhibitor. The widespread CTX-M-14 and CTX-M-15 β-lactamases have an 83% sequence identity. In this study, we show that BLIP weakly inhibits CTX-M-14 but potently inhibits CTX-M-15. The structure of the BLIP/CTX-M-15 complex reveals that binding is associated with a conformational change of an active site loop of β-lactamase. Surprisingly, the loop structure in the complex is similar to that in a drug-resistant variant (N106S) of CTX-M-14. We hypothesized that the pre-established favorable loop conformation of the N106S mutant would facilitate binding. The N106S substitution results in a ~100- and 10-fold increase in BLIP inhibition potency for CTX-M-14 and CTX-M-15, respectively. Thus, this indicates that an active site loop in β-lactamase toggles between conformations that control antibiotic hydrolysis and inhibitor susceptibility. These findings highlight the role of accessible active site conformations in controlling enzyme activity and inhibitor susceptibility as well as the influence of mutations in selectively stabilizing discrete conformations.

There is a focus on sustainability when manufacturing materials. Utilizing biobased materials and replacing fossil‐based products is the main research focus. Bio‐composite materials are applied to packaging, filler coatings, and pharmaceuticals. Here, we used the leaves of the agro‐waste plant Albizia lebeck L. to extract cellulose. Chemical treatment causing strong acid hydrolysis successfully extracted the cellulose content from the leaves. The cellulose obtained was then strengthened with polylactic acid to make a biobased film for future applications. Fourier transform spectroscopy, scanning electron microscopy, thermal analysis, particle size analysis, visible UV and elemental analysis were all used to characterize the extracted cellulose. SEM and mechanical property analysis were used to check and describe the quality of the reinforced biofilm. The greatest cellulose yield from this raw material was 50.2%. The crystallinity index and crystallite size (CI 70.3% and CS 11.29 nm) were high in the extracted cellulose. The TG (DTG) curve analysis derivative revealed cellulose particle breakdown was initiated around 305.2°C and can endure temperatures up to 600°C. Biofilms reinforced with polylactic acid cellulose (1, 2, 3, and 5% by weight %) exhibited a smooth and parallel surface. As the filler concentration increased, minor agglomeration occurred. The tensile strength of pure polylactic acid (PLA) (34.72 MPa) was extended up to 38.91 MPa for 5% filler. Similarly, Young's modulus also increased to 5.24 MPa. However, the elongation break decreases with the increase of filler content, and the least value of decrease is 7.5 MPa. Concerning prospective implementations, it is expected that the biobased film and cellulose particles will prove to be more functional. [ABSTRACT FROM AUTHOR]

Over the past decade, significant progress has been made in creating environmentally friendly products using natural resources. Plant fibers, also known as lignocellulosic fibers, are hydrophilic due to the interaction and attraction between water molecules and the hydroxyl groups present in their components. The inherent hydrophilicity of plant fibers often prevents them from interacting effectively with hydrophobic polymer matrices. In order to improve the adhesion between plant fibers and the matrix, it is necessary to modify the surface of the fibers. Commonly used chemical processes include mercerization, silane treatment, acetylation, permanganate treatment, acrylation, benzoylation, peroxide treatment, stearic acid treatment, isocyanate treatment and sodium chlorite intervention. The desirability of chemically modifying the surface of plant fibers has declined due to several limitations. Plant fibers can be modified in an environmentally friendly way by various methods, such as plasma therapy and treatments using fungi, enzymes and bacteria. This part provides an analysis of the impact of different environmentally friendly surface modification techniques on the properties of plant fibers and reinforced polymers. [ABSTRACT FROM AUTHOR]

This study explores the impact of an adiabatic obstacle on the symmetry of temperature, flow, and electric charge fields during electrohydrodynamic (EHD) natural convection. The configuration studied involves a square, differentially heated cavity with an adiabatic obstacle subjected to a destabilizing thermal gradient and a potential difference between horizontal walls. A numerical analysis was performed using the finite volume method combined with Patankar's "blocked-off-regions" technique, employing an in-house FORTRAN code. The study covers a range of dimensionless electrical Rayleigh numbers (0 to 700) and thermal Rayleigh numbers (102 to 105), with various obstacle positions. Key findings indicate that while the obstacle reduces heat transfer, this can be counterbalanced by electric field effects, achieving up to 165% local heat transfer improvement and 100% average enhancement. Depending on the obstacle's position and size, convective transfer can increase by 27% or decrease by 21%. The study introduces five multiparametric mathematical correlations for rapid Nusselt number determination, applicable to numerous engineering scenarios. This work uniquely combines passive (adiabatic obstacle) and active (electric field) techniques to control heat transfer, providing new insights into the flow behaviour and charge distribution in electro-thermo-hydrodynamic systems. [ABSTRACT FROM AUTHOR]

EPH receptors (EPHs), the largest family of tyrosine kinases, phosphorylate downstream substrates upon binding of ephrin cell surface-associated ligands. In a large cohort of endometriotic lesions from individuals with endometriosis, we found that EPHA2 and EPHA4 expressions are increased in endometriotic lesions relative to normal eutopic endometrium. Because signaling through EPHs is associated with increased cell migration and invasion, we hypothesized that chemical inhibition of EPHA2/4 could have therapeutic value. We screened DNA-encoded chemical libraries (DECL) to rapidly identify EPHA2/4 kinase inhibitors. Hit compound, CDD-2693, exhibited picomolar/nanomolar kinase activity against EPHA2 (Ki: 4.0 nM) and EPHA4 (Ki: 0.81 nM). Kinome profiling revealed that CDD-2693 bound to most EPH family and SRC family kinases. Using NanoBRET target engagement assays, CDD-2693 had nanomolar activity versus EPHA2 (IC50: 461 nM) and EPHA4 (IC50: 40 nM) but was a micromolar inhibitor of SRC, YES, and FGR. Chemical optimization produced CDD-3167, having picomolar biochemical activity toward EPHA2 (Ki: 0.13 nM) and EPHA4 (Ki: 0.38 nM) with excellent cell-based potency EPHA2 (IC50: 8.0 nM) and EPHA4 (IC50: 2.3 nM). Moreover, CDD-3167 maintained superior off-target cellular selectivity. In 12Z endometriotic epithelial cells, CDD-2693 and CDD-3167 significantly decreased EFNA5 (ligand) induced phosphorylation of EPHA2/4, decreased 12Z cell viability, and decreased IL-1β-mediated expression of prostaglandin synthase 2 (PTGS2). CDD-2693 and CDD-3167 decreased expansion of primary endometrial epithelial organoids from patients with endometriosis and decreased Ewing's sarcoma viability. Thus, using DECL, we identified potent pan-EPH inhibitors that show specificity and activity in cellular models of endometriosis and cancer. [ABSTRACT FROM AUTHOR]

Cooperative interactions between amino acids are critical for protein function. A genetic reflection of cooperativity is epistasis, which is when a change in the amino acid at one position changes the sequence requirements at another position. To assess epistasis within an enzyme active site, we utilized CTX-M β-lactamase as a model system. CTX-M hydrolyzes β-lactam antibiotics to provide antibiotic resistance, allowing a simple functional selection for rapid sorting of modified enzymes. We created all pairwise mutations across 17 active site positions in the β-lactamase enzyme and quantitated the function of variants against two β-lactam antibiotics using next-generation sequencing. Context-dependent sequence requirements were determined by comparing the antibiotic resistance function of double mutations across the CTX-M active site to their predicted function based on the constituent single mutations, revealing both positive epistasis (synergistic interactions) and negative epistasis (antagonistic interactions) between amino acid substitutions. The resulting trends demonstrate that positive epistasis is present throughout the active site, that epistasis between residues is mediated through substrate interactions, and that residues more tolerant to substitutions serve as generic compensators which are responsible for many cases of positive epistasis. Additionally, we show that a key catalytic residue (Glu166) is amenable to compensatory mutations, and we characterize one such double mutant (E166Y/N170G) that acts by an altered catalytic mechanism. These findings shed light on the unique biochemical factors that drive epistasis within an enzyme active site and will inform enzyme engineering efforts by bridging the gap between amino acid sequence and catalytic function. [ABSTRACT FROM AUTHOR]

In this study the recent developments in raw materials, manufacturing processes, and applications of natural fiber composites (NFCs) were reviewed. Natural fibers can represent a substitute for man-made fibers (including glass, aramid, and carbon) in a variety of biocomposite applications. Physical and chemical properties of the natural fibers are given and compared with the synthetic fibers. Advantages and disadvantages of NFCs in comparison with synthetic fibers such as glass and carbon fibers have been proposed. Criteria are described for the selection and processing of natural fibers for polymer composites used in different sectors such as automotive and building industries. The nanocellulose production methods, unique properties, and its recent industrial application in various sectors are given. This short review on NFCs considers their chemical, physical, and mechanical characteristics, as well as their various applications. [ABSTRACT FROM AUTHOR]

Mycelium from fungi can serve as the matrix or as a self-grown binder in a biocomposite. The reinforcing component may consist of various combinations of agro-based waste in short fiber or powder form. The complexity of their development is linked not only to the selection of the substrate, but also to the growth conditions of the mycelial material and its consolidation in a final form by the temperature increase that takes place. These materials have initially been proposed as a replacement for polystyrene foams, and the characterization is concentrated on compression performance and acoustic and thermal insulation properties. The present review concentrates on substrates that originated from the large productive system based on hemp (shives or hurds, waste fibers, and mats). Attention is paid to the performance obtained and to the amount of waste that is possibly employed to serve as the substrate. [ABSTRACT FROM AUTHOR]