Embark on a journey into the captivating world of Biomolecular Interactions and Networks with this innovative review, where science meets artistry. Our exploration transcends traditional boundaries, weaving together the rhythmic dance of protein–protein interactions, the dynamic melodies of signaling pathways, and the harmonious integration of omics data.

Introduction: In this entrancing introduction, we cast a spotlight on the grand stage where biomolecular interactions unfold, emphasizing their role as the orchestrators of cellular symphonies. We invite readers to join us on this vibrant expedition, celebrating the intricacies that shape life at the molecular level.

Methods: Our methodological voyage is nothing short of groundbreaking. Imagine peering into the secret conversations of proteins through avant-garde techniques like yeast two-hybrid screens and mass spectrometry, unveiling a kaleidoscope of connections. Visualize the heartbeat of cells captured in real-time with cutting-edge live-cell imaging, and witness the integration of omics data as we decipher the code of cellular communication through computational masterpieces.

Results: The stage is set, and the results are a breathtaking fusion of science and art. Recent revelations paint a vivid canvas of protein–protein interactions, each stroke revealing a new chapter in the biomolecular narrative. Live-cell imaging adds dynamic hues to our understanding of signaling pathways, while the integration of omics data unfolds intricate networks reminiscent of a cosmic tapestry.

Conclusions: As the curtains fall, we arrive at a crescendo of knowledge. This review not only encapsulates the current state of Biomolecular Interactions and Networks but also propels us into the future of collaborative discovery. Join us in decoding the symphony of life, where the language of cells becomes a universal melody with transformative potential for both scientific understanding and targeted therapeutic innovations.

Introduction: S100A8 protein belongs to the EF-hand family of calcium-binding proteins and is involved in inflammatory processes, immune response, andthe pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD). According to available clinical data, the level of S100A8 is increased in the cerebrospinal fluid of AD patients. Although data in the literaturesuggest an involvement of S100A8 in the regulation of amyloid β peptide (Aβ) metabolism involved in AD progression, the possible interaction between S100A8 and Aβ remains unexplored. To this end, we aimed to studythis aspect and its relevance to Aβ fibrillation.

Methods: The parameters of interaction between recombinant human S100A8 and monomeric recombinant human Aβ40/42 were studied using bio-layer interferometry. The Aβ40 fibrillation in the absence/presence of S100A8 was monitored using a thioflavin T (ThT) fluorescence assay.

Results: Ca²⁺-loaded S100A8 was shown to bind monomeric Aβ40/42 with equilibrium dissociation constants of 2.7±1.0 µM and 2.8±0.7 µM, respectively. S100A8 dramatically suppressed Aβ40 fibrillation, as evidenced by a 12–23-fold decrease in maximum ThT fluorescence intensity.

Conclusion: S100A8 interacts with Aβ40/42 monomer and inhibits Aβ40 fibrillation in vitro, thereby suggesting that S100A8 may be involved in the control of Aβ deposition in AD.

This study was supported by Russian Science Foundation grants № 20-74-10072 (https://rscf.ru/project/20-74-10072/) and № 19-14-00289-П (https://rscf.ru/project/22-14-35043/).

The contemporary world grapples with a critical issue—the effective management of waste. The surge in population and industrial activities has caused a substantial rise in waste generation, contributing to environmental degradation, resource depletion, and various sustainability challenges. In addressing this dilemma, the practice of garbage classification has emerged as a crucial solution. It plays a significant role in mitigating the adverse impacts of waste on the environment and fostering a more sustainable approach to waste management.

Our project addresses the critical issue of garbage classification by leveraging the YOLOv7 real-time object detection framework. The first step involves assembling a comprehensive dataset of garbage items and categorizing them into several distinct groups. To ensure precise categorization of the images, we adapt YOLOv7, a powerful tool for real-time object detection. This project encompasses various stages, including data collection, preparation, and labeling, with a particular emphasis on employing the most effective methods for data labeling—an essential step in the project.

Additionally, the process involves data preprocessing, model training, evaluation, and real-time inference. Via these comprehensive steps, our project aims to contribute to the advancement of garbage classification methodologies, ultimately promoting a more sustainable and efficient approach to waste management.

Furthermore, it is worth noting that some of the achieved values closely align with the performance of YOLOv4, a more advanced iteration of YOLOv3.

Silver nanoparticles (Ag NPs) have drawn a lot of interest because of their antibacterial activity. However, their synthesis by chemical methods is potentially harmful; this is the reason why the use of plant extract for synthesis constitutes a simple, effective and safe alternative solution.

In this work, Ag NPs were synthesized by the precipitation method; silver nitrate was used as precursor and the extract of Rosmarinus officinalis was used as a reducing as well as capping agent.

They were characterized using X-ray diffraction DRX, UV-visible spectrometry and Fourier-transform infrared spectroscopy (FTIR), and they were also examined for their antimicrobial properties by using the agar diffusion method against gram-negative and gram-positive bacteria.

XRD analysis confirms the crystalline nature of the NPs, with a face-centered cubic (fcc) structure, and reveals that the average crystallite sizes of the Ag NPs are 30nm.

The UV-visible spectrum showed absorption peaks at 220-360 which revealed the presence of functional groups (phenolics, flavonoids, tannins…), and FTIR analysis confirmed their existence and that these biomolecule compounds were not only responsible for the reduction but also the capping of Ag NPs.

Ag NPs exhibited antibacterial activity against both bacteria (gram-negative strain of E. coli BLSE, K. pneumoniae carb-, and gram-positive strain of E. fecalis ATCC292112, S. aureus ATCC25923) withlarge zones of inhibition, respectively (50.7mm, 10.34mm, 17.87 mm, 10.72mm)

The present study showed that the extract of Rosmarinus officinalis can be used as reducing and capping agent to synthesize Ag NPs that present a highly bactericidal effect.

Abstract

Introduction: Apart from lacking macrofilaricidal activity, the anti-filarial drugs DEC, albendazole and ivermectin are also often associated with several severe side-effects. Therefore, macrofilaricidal drugs which are non-toxic and have minimal side effects are needed as better treatment options.

Methods: An ethanol extract of Ocimum sanctum (EOS) leaves was prepared and its anti-filarial activity was investigated by a combined biochemical and proteomics approach. Equal size and number of adult Setaria cervi worms were exposed to EOS following which the anti-oxidant activities were estimated and proteomic profile was studied by two-dimensional electrophoresis. The differentially expressed proteins were subjected to drug docking against EOS bioactive compounds.

Results: The EOS significantly reduced the viability of adult female Setaria cervi after 6 hr of incubation at 37^o C. An increase in lipid peroxidation (51.92 %), protein carbonylation (48.99%), and NADPH oxidase (88.88 %) activity and a decrease in the glutathione (GSH) (-39.23 %), glutathione reductase (GR) (-60.17 %), and glutathione S- transferase (GST) (-50.48 %) activity were observed after EOS treatment. There were alterations in the proteomic profile of EOS-treated S. cervi at 250 µg/ml concentration in comparison to the control group of S. cervi, and 2D gel electrophoresis revealed 20 downregulated and 11 upregulated protein spots in the treated parasites. Further, in drug docking analysis, EOS bioactive compounds eugenol, kaempferol, luteolin, rutin and rosmarinic acid showed high binding affinity with the major differentially expressed proteins.

Conclusion: Herein, we report for the first time that the anti-filarial activity of EOS is largely mediated by its impact on the anti-oxidant, energy metabolism and stress response systems of the filarial parasites.

Human skin is constantly exposed to various endogenous and exogenous factors, including UV radiation and vitamin deficiency, which can influence the earlier appearance of visible wrinkles and decrease skin firmness and elasticity. This process is related to decreased collagen I synthesis in the dermis. However, the use of retinol derivatives, synthetic molecules, and growth factors is associated with significant adverse effects, low bioavailability, and instability in dermatological products. Thus, our research was focused on the investigation of a novel plant-based combination for the stimulation of collagen I synthesis in deep skin layers and the prevention of accelerated skin ageing. Aloe barbadensis leaf extract, trimethylglycine, and panthenol were chosen as potential candidates using in silico modelling. A Way2Drug tool predicted anti-inflammatory, anti-psoriatic, and antioxidant activities beneficial for the prophylaxis of skin ageing. An in vitro study was conducted to determine collagen I synthesis in skin fibroblasts in the presence of single substances and their composition using a colorimetric analysis. It was revealed that the combination of Aloe barbadensis leaf extract, trimethylglycine, and panthenol in a specific mass ratio of 2:4:1 and at a concentration of 0.5% significantly increased the amount of collagen I in the skin fibroblasts by up to +18% within 24 hours (p<0.001). This effect was comparable to that of TGF-β1 (10 ng/mL), with a 37% collagen I increase (p<0.001). The single compounds and the combination of Aloe barbadensis leaf extract and trimethylglycine showed a negative effect on collagen I synthesis, with an unpredictable decrease in this protein in fibroblasts. The combination of the compounds made it possible to achieve a synergistic effect, boosting the natural rejuvenation process in fibroblasts. Overall, the results indicate that the developed plant-based composition in the specific mass ratio and concentration given above could increase collagen I synthesis and can be considered a promising substance for dermatological products with reverse anti-ageing effects.

Introduction:

Candia auris is a fungal pathogen that has emerged as a global threat in recent years due to its resistance to multiple antifungal drugs and its ability to cause invasive infections, especially in immunosuppressed patients. Understanding the molecular mechanisms of pathogenesis and drug resistance in Candida auris is crucial for the development of effective treatment strategies. The role of lysine methyltransferases, particularly the SMYD family, in the regulation of gene expression and protein function is of great interest in the context of fungal pathogenesis. Investigating the potential involvement of SMYD proteins in Candida auris could provide valuable information on the mechanisms underlying its virulence and drug resistance.

Methods:

In this paper, the uncharacterized SMYD family proteins of Candida auris are considered for in silico functional and structural characterizations. Using a combination of sequence analysis, structural modeling, and phylogenetic profiling tools, the intricate annotation process of lysine methyltransferases will be thoroughly explored.

Results:

The structural similarities between the SMYD members in Saccharomyces cerevisiae, Candida albicans, and their human counterparts suggest that studying the function of Set5 and Set6 in yeast could provide relevant information about the role of SMYD proteins in chromatin association, genome stability, and gene expression regulation. Further, the Candida auris SMYD family was expanded with a novel, uncharacterized member. This member was functionally characterized using protein sequences, phylogeny, structural modelling, and binding studies.

Conclusions:

The study provides knowledge about SMYD methyltransferase proteins in Candida auris using in silico approaches, shedding light on their physiological roles. In conclusion, the emerging role of SMYD proteins in various physiological processes and their implications in cancer pathophysiology, combined with their potential involvement in fungal pathogenesis, highlight the importance of further research on members of the SMYD protein family in various biological systems.

Prostate cancer is one of the leading causes of death among men. Our study focuses on seeking new compounds and combinations to diminish the severe side effects of classical anticancer drugs for treating this type of cancer. In this study, we investigated and compared the classical anticancer drugs and non-classical compounds docetaxel, Au porphyrin, and the plant lectin jacalin, and in different combinations on the prostate cancer cell line PC3.

Jacalin, isolated from jackfruit seeds by affinity chromatography on immobilized galactose, specifically recognizes the tumor-associated Thomsen–Friedenreich antigen. The present investigation shows the interaction of jacalin with Au porphyrin, registering conformational changes within the protein due to the binding. From the titration curve, the affinity of 1.8±0.39 µM for the jacalin–Au porphyrin complex was calculated.

In vitro experiments with PC3 cells treated with docetaxel or Au porphyrin indicated a decrease in cell viability, compared with the jacalin–Au porphyrin complex, as registered by viability assays.

The IC₅₀ for Au porphyrin and for docetaxel were studied and indicated that the calculated IC₅₀ for docetaxel was 8 orders of magnitude higher than that for Au porphyrin.

Our results demonstrate the effects of three compounds as well as the effects of their combinations upon treatment of PC3 cells. Molecular mechanisms will be studied in future experiments.

The emergence of antibiotic resistance makes the development of a
new generation of powerful antimicrobials able to kill super bugs more essential than ever. Linear scorpion venom peptides are a small group of venom peptides that display antimicrobial, anticancer, and anti-inflammatory activities, although, in many cases, they exhibit strong hemolytic activity hinderingtheir further development.
Here, we present an improved synthesis of Mucroporin, a linear scorpion peptide of 17 amino acids, isolated from the Chinese Scorpion Lychas Mucronatus. The synthesis was conducted on a Microwave Peptide Synthesizer (Biotage Initiator+) by using an ultra-fast method at elevated temperature, 90oC, avoiding some common steps in the conventional methods and reducing the total synthesis time by 40% and the total waste by 50% without affecting the purity of the crude peptide, which was calculated to 90%, making the final purification easier than ever. The synthesis was performed by using N-butyl-2-pyrrolidone (NBP), a green
alternative to DMF solvent, which is under restriction for use in therapeutic peptides as ofDecember 2023 in EU.
Mucroporin was tested for its antimicrobial activity against gram-positive and gram-negative bacterial strains (Escherichia coli, Staphylococcus epidermidis, Neisseria subflava and Streptococcus pneumoniae Strain) by the serial dilution method in liquid cultures of bacteria with a cell density of ~2x 105 CFU/ml in different concentrations and incubated for 24 hours, and then the optical density was measured at 600nm. Ampicillin was used as a positive control at a concentration of 100μg/ml. The peptide completely inhibited the growth of Staphylococcus
epidermidis and Streptococcus pneumoniae, as expected from earlier studies. Of particular interest is the inhibitory activity of Neisseria subflava at a final concentration of 120μg/ml.
This is the first time that mucroporin has ever been reported to be effective against gram-negative strains; therefore, its activity against Neisseria subflava is of particular interest.

The identification of novel drugs for neurodegenerative diseases such as Alzheimer’s and Parkinson’s are complex as they are associated with more than one distinct cause and multiple disease mechanisms with multiple drug targets. For Alzheimer’s disease (AD), despite extensive research, there are currently no drugs available that can improve clinical symptoms permanently and with moderate efficacy. Numerous target-specific chemical or biologic drugs, proposed earlier, were either abandoned due to their limited potency to a single mechanistic target enzyme or failed in clinical trials due to adverse side-effects and impaired blood--brain barrier efficacy. At this outset, finding an efficient multi-target drugs with adequate bioavailability and drug likeliness against this AD is essential. This work focuses on an in-house strategically designed database of quinazolinone derivatives and performed a detailed ADMET screening to explore the pharmacokinetic actions of the molecules. A select set of lead molecules were further probed into their sequential molecular docking towards the simultaneous inhibition of three therapeutic targets of AD (acetylcholinesterase, butyrylcholinesterase, and β-secretase). The effort has successfully identified few novel inhibitors of AD pathogenesis with ‘multi-targeted potency’. This finding opens the door for further research into these lead compounds as potential therapeutics for the efficient triple inhibition of three crucial enzymes of amyloid-based and cholinergic mechanisms for AD pathogenesis. The report additionally unlocks an innovative ‘One Drug-Multiple Target’ ligand construction approach to deal with the complicated multifunctional nature of AD.