De Novo Discovery of Pseudo-Natural Prenylated Macrocyclic Peptide Ligands.

Prenylation of peptides is widely observed in the secondary metabolites of diverse organisms, granting peptides unique chemical properties distinct from proteinogenic amino acids. Discovery of prenylated peptide agents has largely relied on isolation or genome mining of naturally occurring molecules. To devise a platform technology for de novo discovery of artificial prenylated peptides targeting a protein of choice, here we have integrated the thioether-macrocyclic peptide (teMP) library construction/selection technology, so-called RaPID (Random nonstandard Peptides Integrated Discovery) system, with a Trp-C3-prenyltransferase KgpF involved in the biosynthesis of a prenylated natural product. This unique enzyme exhibited remarkably broad substrate tolerance, capable of modifying various Trp-containing teMPs to install a prenylated residue with tricyclic constrained structure. We constructed a vast library of prenylated teMPs and subjected it to in vitro selection against a phosphoglycerate mutase. This selection platform has led to the identification of a pseudo-natural prenylated teMP inhibiting the target enzyme with an IC50 of 30 nM. Importantly, the prenylation was essential for the inhibitory activity, enhanced serum stability, and cellular uptake of the peptide, highlighting the benefits of peptide prenylation. This work showcases the de novo discovery platform for pseudo-natural prenylated peptides, which is readily applicable to other drug targets.

A sustainable, low-cost carbonaceous hydrochar adsorbent for methylene blue adsorption derived from corncobs.

In this study, activated carbon from corncobs was successfully synthesized by hydrothermal carbonization and hydrochemical activation at low temperatures, followed by pyrolysis. A developed method of hydrochemical activation of hydrochar that uses only small amounts of chemicals is a promising approach. After activation, the activator residues in the hydrothermal product can constantly act as a chemical activator during pyrolysis to form corncob-activated carbon (AHC-KOH), which had specific surface area of 965.028 m2/g and oxygenated functional groups of 0.3780 mmol/g, 31.67 and 4 times, respectively, of those of the inactivated sample. AHC-KOH was used to study the adsorption characteristics of methylene blue (MB). The MB adsorption efficiency of AHC-KOH was the highest at 489.560 mg/g, which was considerably higher than that of activated carbons produced from other biomasses. The isotherm equilibrium and adsorbent kinetics parameters of MB adsorption on AHC-KOH were also determined using the Langmuir isotherm model (R2 = 0.99) and pseudo-second-order kinetic model (R2 > 0.99). Thus, the results indicate that an inexpensive adsorbent produced from corncobs using the above method is a promising material for wastewater treatment.

Reference the seabed topographic depth observations based on the national mean dynamic topography model.

The mean sea surface in different regions is non-equipotential, rendering Vietnam's traditional approach, which relies on the Hon-Dau tide gauge station as a reference, not yet scientifically invalid. To overcome this, our study utilized the Vietnam national mean dynamic topography model (MDTVN22) for depth observations, particularly in the Gulf of Tonkin. Covering 3430 monitoring sites in Hai Phong and 813 sites in Quang Ninh, our experiments highlighted a 5 to 6 mm difference between the mean sea surface and MDTVN22 references. •Our research establishes a resilient methodology, integrating shore tide gauge station data and the MDTVN22 model, aimed at enhancing precision in depth observations.•Validation experiments in Hai Phong demonstrate a minimal discrepancy of ±0.006 m between measurements obtained from the traditional mean sea surface and the MDTVN22 model.•These findings underscore the significance of adopting the MDTVN22 model for improved accuracy in assessing Vietnam's seabed topography.

Enhanced growth performance of abi5 plants under high salt and nitrate is associated with reduced nitric oxide levels.

Numerous environmental stresses have a significant impact on plant growth and development. By 2050, it is anticipated that high salinity will destroy more than fifty percent of the world's agricultural land. Understanding how plants react to the excessive use of nitrogen fertilizers and salt stress is crucial for enhancing crop yield. However, the effect of excessive nitrate treatment on plant development is disputed and poorly understood; so, we evaluated the effect of excessive nitrate supply and high salinity on abi5 plant growth performance. We demonstrated that abi5 plants are tolerant to the harmful environmental conditions of excessive nitrate and salt. abi5 plants have lower amounts of endogenous nitric oxide than Arabidopsis thaliana Columbia-0 plants due to their decreased nitrate reductase activity, caused by a decrease in the transcript level of NIA2, a gene encoding nitrate reductase. Nitric oxide appeared to have a critical role in reducing the salt stress tolerance of plants, which was diminished by an excess of nitrate. Discovering regulators such as ABI5 that can modulate nitrate reductase activity and comprehending the molecular activities of these regulators are crucial for the application of gene-editing techniques. This would result in the appropriate buildup of nitric oxide to increase the production of crops subjected to a variety of environmental stresses.

The Loss of Function of the NODULE INCEPTION-Like PROTEIN 7 Enhances Salt Stress Tolerance in Arabidopsis Seedlings.

Plants acquire nitrogen, an essential macronutrient, from the soil as nitrate. Since nitrogen availability is a major determinant of crop productivity, the soil is amended with nitrogenous fertilizers. Extensive use of irrigation can lead to the accumulation of salt in the soil, which compromises crop productivity. Our characterization of NODULE INCEPTION (NIN)-like PROTEIN 7 (NLP7), a transcription factor regulating the primary response to nitrate, revealed an intersection of salt stress and nitrate metabolism. The growth of loss-of-function mutant nlp7 was tolerant to high salinity that normally reduces the fresh weight and chlorophyll and protein content of wild type (Col-0). On a medium with high salinity, the nlp7 experienced less stress, accumulating less proline, producing less nitric oxide (NO) and reactive oxygen species (ROS), and expressing lower transcript levels of marker genes, such as RD29A and COR47, than Col-0. Nevertheless, more sodium ions were translocated to and accumulated in the shoots of nlp7 than that of Col-0. Since nlp7 also expressed less nitrate reductase (NR) activity, nitrate accumulated to abnormally high levels with or without salinity. We attributed the enhanced salt tolerance of nlp7 to the balanced accumulation of nitrate anions and sodium cations. Our results suggest that nitrate metabolism and signaling might be targeted to improve salt tolerance.

Adsorption isotherms and kinetic modeling of methylene blue dye onto a carbonaceous hydrochar adsorbent derived from coffee husk waste.

In this study, activated carbon in the form of carbonaceous hydrochar adsorbents with highly functionalized surface-active sites were produced from coffee husk waste via hydrothermal carbonization under low-temperature conditions (180 °C) and subsequent chemical activation. Thereafter, the hydrochars were characterized using diverse analytical techniques, and batch experiments of methylene blue (MB) adsorption were performed under various operating conditions. The results indicated that the activated hydrochar (AH) had a larger specific surface area (862.2 m2 g-1) compared to that of its carbonaceous precursor (33.7 m2 g-1). The maximum MB sorption capacity of the hydrochar activated with potassium hydroxide was extremely high (415.8 mg g-1 at 30 °C). In addition, adsorption isotherms and kinetics were studied using experimental data fitting to further understand and describe the dynamic equilibrium, dynamic kinetics, and mechanism of MB adsorption onto the prepared hydrochars. As compared to the Freundlich isotherm model, the Langmuir isotherm model provided a better fit with the experimental data exhibiting a maximum monolayer adsorption capacity of 418.78 mg g-1. The linear pseudo-second-order kinetic model was found to be suitable for describing the adsorptive kinetics of the hydrochar. The results demonstrated the immense potential of coffee husk waste to produce activated carbon as an alternative green hydrochar that can be applied to dye removal from wastewater as well as improvement of waste management.

Antioxidant activities of thiosemicarbazones from substituted benzaldehydes and N-(tetra-O-acetyl-ß-D-galactopyranosyl)thiosemicarbazide.

Reaction of N-(2,3,4,6-tetra-O-acetyl-ß-d-galactopyranosyl)thiosemicarbazide and different substituted benzaldehydes gave some new substituted benzaldehyde N-(2,3,4,6-tetra-O-acetyl-ß-d-galactopyranosyl)thiosemicarbazones. The reaction was performed using conventional and microwave-assisted heating methods. The structures of thiosemicarbazones were confirmed by spectroscopic (IR, (1)H NMR, (13)C NMR and ESI-MS) method. The antioxidant activity of these thiosemicarbazones was evaluated in vitro and in vivo, and it's shown that some of these compounds had significant antioxidant activity. Amongst the compounds screened for antioxidant activity, thiosemicarbazones 4a, 4b and 4c showed good antioxidant activity on DPPH. The compounds 4g, 4i, 4l caused significant elevation of SOD activity and 4e, 4g, 4i, 4l had higher catalase activity, and only compounds 4c and 4f expressed the GSH-Px activity.