A magnetically enabled simulation of microgravity represses the auxin response during early seed germination on a microfluidic platform

For plants on Earth, the phytohormone auxin is essential for gravitropism-regulated seedling establishment and plant growth. However, little is known about auxin responses under microgravity conditions due to the lack of a tool that can provide an alteration of gravity. In this paper, a microfluidic negative magnetophoretic platform is developed to levitate Arabidopsis seeds in an equilibrium plane where the applied magnetic force compensates for gravitational acceleration. With the benefit of the microfluidic platform to simulate a microgravity environment on-chip, it is found that the auxin response is significantly repressed in levitated seeds. Simulated microgravity statistically interrupts auxin responses in embryos, even after chemical-mediated auxin alterations, illustrating that auxin is a critical factor that mediates the plant response to gravity alteration. Furthermore, pretreatment with an auxin transportation inhibitor (N-1-naphthylphthalamic acid) enables a decrease in the auxin response, which is no longer affected by simulated microgravity, demonstrating that polar auxin transportation plays a vital role in gravity-regulated auxin responses. The presented microfluidic platform provides simulated microgravity conditions in an easy-to-implement manner, helping to study and elucidate how plants correspond to diverse gravity conditions; in the future, this may be developed into a versatile tool for biological study on a variety of samples.

Potential COVID-19 Drug Candidates Based on Diazinyl-Thiazol-Imine Moieties: Synthesis and Greener Pastures Biological Study

A novel series of 1-aryl-N-[4-phenyl-5-(arylazo)thiazol-2-yl)methanimines has been synthesized via the condensation of 2-amino-4-phenyl-5-arylazothiazole with various aromatic aldehydes. The synthesized imines were characterized by spectroscopic techniques, namely 1H and 13C NMR, FTIR, MS, and Elemental Analysis. A molecular comparative docking study for 3a–f was calculated, with reference to two approved drugs, Molnupiravir and Remdesivir, using 7BQY (Mpro; PDB code 7BQY; resolution: 1.7 A°) under identical conditions. The binding scores against 7BQY were in the range of −7.7 to −8.7 kcal/mol for 3a–f. The high scores of the compounds indicated an enhanced binding affinity of the molecules to the receptor. This is due to the hydrophobic interactions and multi-hydrogen bonds between 3a–f ligands and the receptor’s active amino acid residues. The main aim of using in silco molecular docking was to rank 3a–f with respect to the approved drugs, Molnupiravir and Remdesivir, using free energy methods as greener pastures. A further interesting comparison presented the laydown of the ligands before and after molecular docking. These results and other supporting statistical analyses suggested that ligands 3a–f deserve further investigation in the context of potential therapeutic agents for COVID-19. Free-cost, PASS, SwissADME, and Way2drug were used in this research paper to determine the possible biological activities and cytotoxicity of 3a–f.

Synthesis, Physicochemical and Biological Study of Gallium-68- and Lutetium-177-Labeled VEGF-A165/NRP-1 Complex Inhibitors Based on Peptide A7R and Branched Peptidomimetic

Neuropilin-1 (NRP-1) is a surface receptor found on many types of cancer cells. The overexpression of NRP-1 and its interaction with vascular endothelial growth factor-165 (VEGF165) are associated with tumor growth and metastasis. Therefore, compounds that block the VEGF165/NRP-1 interaction represent a promising strategy to image and treat NRP-1-related pathologies. The aim of the presented work was to design and synthesize radioconjugates of two known peptide-type inhibitors of the VEGF165/NRP-1 complex: A7R peptide and its shorter analog, the branched peptidomimetic Lys(hArg)-Dab-Pro-Arg. Both peptide-type inhibitors were coupled to a radionuclide chelator (DOTA) via a linker (Ahx) and so radiolabeled with Ga-68 and Lu-177 radionuclides, for diagnostic and therapeutic uses, respectively. The synthesized radioconjugates were tested for their possible use as theranostic-like radiopharmaceuticals for the imaging and therapy of cancers that overexpress NRP-1. The obtained results indicate good efficiency of the radiolabeling reaction and satisfactory stability, at least 3t1/2 for the 68Ga- and 1t1/2 for the 177Lu-radiocompounds, in solutions mimicking human body fluids. However, enzymatic degradation of both the studied inhibitors caused insufficient stability of the radiocompounds in human serum, indicating that further modifications are needed to sufficiently stabilize the peptidomimetics with inhibitory properties against VEGF165/NRP-1 complex formation.

Post-vaccine COVID-19 in patients with multiple sclerosis or neuromyelitis optica

Introduction: Recent studies suggested that anti-CD20 and fingolimod may be associated with lower anti-spike protein-based immunoglobulin-G response following COVID-19 vaccination. We evaluated if COVID-19 occurred despite vaccination among patients with multiple sclerosis (MS) and neuromyelitis optica (NMO), using the COVISEP registry. Case series: We report 18 cases of COVID-19 after two doses of BNT162b2-vaccination, 13 of which treated with anti-CD20 and four with fingolimod. COVID-19 severity was mild. Discussion: These results reinforce the recommendation for a third COVID-19 vaccine dose among anti-CD20 treated patients and stress the need for a prospective clinical and biological study on COVID-19 vaccine efficacy among MS and NMO patients.

Stimulation of Sulfonamides Antibacterial Drugs Activity as a Result of Complexation with Ru(III): Physicochemical and Biological Study

Antibiotic resistance is a global problem, and one promising solution to overcome this issue is using metallodrugs, which are drugs containing metal ions and ligands. These complexes are superior to free ligands in various characteristics including anticancer properties and mechanism of action. The pharmacological potential of metallodrugs can be modulated by the appropriate selection of ligands and metal ions. A good example of proper coordination is the combination of sulfonamides (sulfamerazine, sulfathiazole) with a ruthenium(III) ion. This work aimed to confirm that the activity of sulfonamides antibacterial drugs is initiated and/or stimulated by their coordination to an Ru(III) ion. The study determined the structure, electrochemical profile, CT-DNA affinity, and antimicrobial as well as anticancer properties of the synthesized complexes. The results proved that Ru(III) complexes exhibited better biological properties than the free ligands.

Mathematical Investigation and Computers Simulation of Plant Protection Process Taking into Account the Temporary Age Structure and Arbitrary Tropic Functions

The problem of describing the process of protecting agricultural crops in mathematical modeling is relevant. Today, the problem of plant protection attracts the attention of a large circle of scientists in connection with its promising use in priority areas of development of science, technology and agriculture. Mathematical modeling of the process of protecting the planned crop is one of the main tools in predicting the state of natural systems and managing them. One of the most important national economic, social and environmental problems at present is the improvement of systems for protecting agricultural crops from pests. Mathematical modeling of the process of protecting the planned harvest obliges to improve regional systems for protecting cotton on the basis of a targeted ecological and biological study, revealing the specifics of the formation and development of agro ecosystems in intensive crop production. The main task of the integrated method of combating agricultural pests of the plant protection process is the management of agrocenoses of “harmful insects” and “beneficial insects” of species based on the use of biological, chemical methods as a means or a management tool.The use of mathematical methods and computer software products to solve the problem of protecting the planned crop significantly increases the efficiency of planned and economic work and ensure optimal results. In this paper, we consider a mathematical model of the plant protection process, taking into account the temporal age structure and arbitrary trophic functions, formulate the task of plant protection. Necessary and sufficient conditions for the solvability of the plant protection problem with arbitrary trophic functions are found

Chemical Diversity and Antimicrobial Potential of Cultivable Fungi from Deep-Sea Sediments of the Gulf of Mexico

A collection of 29 cultivable fungal strains isolated from deep-sea sediments of the Gulf of Mexico were cultivated under the “one strain, many compounds” approach to explore their chemical diversity and antimicrobial potential. From the 87 extracts tested, over 50% showed antimicrobial activity, and the most active ones were those from cultures grown at 4 °C in darkness for 60 days (resembling deep-sea temperature). PCA analysis of the LC-MS data of all the extracts confirmed that culture temperature is the primary factor in the variation of the 4462 metabolite features, accounting for 21.3% of the variation. The bioactivity-guided and conventional chemical studies of selected fungal strains allowed the identification of several active and specialized metabolites. Finally, metabolomics analysis by GNPS molecular networking and manual dereplication revealed the biosynthetic potential of these species to produce interesting chemistry. This work uncovers the chemical and biological study of marine-derived fungal strains from deep-sea sediments of the Gulf of Mexico.