Small molecular

Residue-level coarse-grained (CG) molecular dynamics (MD) simulation is widely used to investigate slow biological processes that involve multiple proteins, nucleic acids, and their complexes. Biomolecules in a large simulation system are distributed non-uniformly, limiting computational efficiency with conventional methods. Here, we develop a hierarchical domain decomposition scheme with dynamic load balancing for heterogeneous biomolecular systems to keep computational efficiency even after drastic changes in particle distribution...

New thermostable β-1,3-1,4-glucanase (lichenase) designated as Blg29 was expressed and purified from a locally isolated alkaliphilic bacteria Bacillus lehensis G1. The genome sequence of B. lehensis predicted an open reading frame of Blg29 with a deduced of 249 amino acids and a molecular weight of 28.99 kDa. The gene encoding for Blg29 was successfully amplified via PCR and subsequently expressed as a recombinant protein using the E. coli expression system. Recombinant Blg29 was produced as a soluble form and further purified via immobilized metal ion affinity chromatography (IMAC)...

This study investigated nine provinces in northern Morocco and collected 275 skin scraping, 22 bone marrow aspirates, and 89 fine needle aspirations from suspected cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL) patients and potentially infected dogs. Molecular analysis using ITS1 RFLP PCR and RT-PCR revealed a higher prevalence of L. infantum (66.18 %; χ2  = 28.804; df = 1; P-value = 8.01e-08) than L. tropica in skin scraping, with L. infantum being the sole causative agent for both VL and canine leishmaniasis...

Signalling networks are critical for virtually all cell functions. Our current knowledge of cell signalling has been summarised in signalling pathway databases, which, while useful, are highly biassed towards well-studied processes, and do not capture context specific network wiring or pathway cross-talk. Mass spectrometry-based phosphoproteomics data can provide a more unbiased view of active cell signalling processes in a given context, however, it suffers from low signal-to-noise ratio and poor reproducibility across experiments...

Acute mesenteric ischemia (AMI) is a clinically significant vascular and gastrointestinal condition, which is closely related to the blood supply of the small intestine. Unfortunately, it is still challenging to properly discriminate small intestinal tissues with different degrees of ischemia. In this study, hyperspectral imaging (HSI) was used to construct pseudo-color images of oxygen saturation about small intestinal tissues and to discriminate different degrees of ischemia. First, several small intestine tissue models of New Zealand white rabbits were prepared and collected their hyperspectral data...

In aqueous binary solvents with fluorinated alcohols, 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), and aliphatic alcohols, ethanol (EtOH) and 2-propanol (2-PrOH), the denaturation of hen egg white lysozyme (HEWL) with increasing alcohol mole fraction x A has been investigated in a wide view from the molecular vibration to the secondary and ternary structures. Circular dichroism (CD) measurement showed that the secondary structure of α-helix content of HEWL increases on adding a small amount of the fluorinated alcohol to the aqueous solution, while the β-sheet content decreases...

Liquid-liquid phase separation is an intracellular mechanism by which molecules, usually proteins and RNAs, interact and then rapidly demix from the surrounding matrix to form membrane-less compartments necessary for cellular function. Occurring in both the cytoplasm and the nucleus, properties of the resulting droplets depend on a variety of characteristics specific to the molecules involved, such as valency, density, and diffusion within the crowded environment. Capturing these complexities in a biologically relevant model is difficult...

Epigenetic gene silencing induced by expanded repeats can cause diverse phenotypes ranging from severe growth defects in plants to genetic diseases such as Friedreich's ataxia in humans. The molecular mechanisms underlying repeat expansion-induced epigenetic silencing remain largely unknown. Using a plant model with a temperature-sensitive phenotype, we have previously shown that expanded repeats can induce small RNAs, which in turn can lead to epigenetic silencing through the RNA-dependent DNA methylation pathway...

KRAS is the most frequently mutated oncogene in human cancer and facilitates uncontrolled growth through hyperactivation of the RTK/MAPK pathway. The Son of Sevenless homolog 1 (SOS1) protein functions as a guanine nucleotide exchange factor (GEF) for the RAS subfamily of small GTPases and represents a druggable target in the pathway. Using a structure-based drug discovery approach, MRTX0902 was identified as a selective and potent SOS1 inhibitor that disrupts the KRAS:SOS1 protein-protein interaction to prevent SOS1-mediated nucleotide exchange on KRAS and translates into an anti-proliferative effect in cancer cell lines with genetic alterations of the KRAS-MAPK pathway...

The Hippo pathway is a key regulator of tissue growth, organ size, and tumorigenesis. Activating the Hippo pathway by gene editing or pharmaceutical intervention has been proven to be a new therapeutic strategy for treatment of the Hippo pathway-dependent cancers. To now, a number of compounds that directly target the downstream effector proteins of Hippo pathway, including YAP and TEADs, have been disclosed, but very few Hippo pathway activators are reported. Here, we discovered a new class of Hippo pathway activator, YL-602, which inhibited CTGF expression in cells irrespective of cell density and the presence of serum...

The androgen receptor (AR) and estrogen receptor alpha (ERα) are steroid receptor transcription factors with critical roles in the development and progression of prostate and breast cancers. Advances in the understanding of mechanisms underlying the ligand-dependent activation of these transcription factors have contributed to the development of small molecule inhibitors that block AR and ERα actions. These inhibitors include competitive antagonists and degraders that directly bind the ligand binding domains of these receptors, luteinizing hormone releasing hormone (LHRH) analogs that suppress gonadal synthesis of testosterone or estrogen, and drugs that block specific enzymes required for biosynthesis of testosterone or estrogen...

There is an increasing demand for small-diameter blood vessels. Currently, there is no clinically available small-diameter artificial vessel. Bacterial nanocellulose (BNC) has vast potential for applications in artificial blood vessels due to its good biocompatibility. At the same time, medical polyurethane (PU) is a highly elastic polymer material widely used in artificial blood vessels. This study reports a composite small-diameter BNC/PU conduit using a non-solvent-induced phase separation method with the highly hydrophilic BNC tube as the skeleton and the hydrophobic polycarbonate PU as the filling material...

Spray-drying of nucleic acid-based drugs designed for gene therapy or gene knockdown is associated with many advantages including storage stability and handling as well as the possibility of pulmonary application. The encapsulation of nucleic acids in nanoparticles prior to spray-drying is one strategy for obtaining efficient formulations. This, however, strongly relies on the definition of optimal nanoparticles, excipients and spray-drying conditions. Among polymeric nanoparticles, polyethylenimine (PEI)-based complexes with or without chemical modifications have been described previously as very efficient for gene or oligonucleotide delivery...

Cryoconite holes, small meltwater pools on the surface of glaciers and ice sheets, represent extremely cold ecosystems teeming with diverse microbial life. Cryoconite holes exhibit greater susceptibility to the impacts of climate change, underlining the imperative nature of investigating microbial communities as an essential module of polar and alpine ecosystem monitoring efforts. Microbes in cryoconite holes play a critical role in nutrient cycling and can produce bioactive compounds, holding promise for industrial and pharmaceutical innovation...

Microbial herbicide degradation is an efficient bioremediation method. In this study, a strain of Streptomyces nigra, LM01, which efficiently degrades atrazine and nicosulfuron, was isolated from a corn field using a direct isolation method. The degradation effects of the identified strain on two herbicides were investigated and optimized using an artificial neural network. The maximum degradation rates of S. nigra LM01 were 58.09 % and 42.97 % for atrazine and nicosulfuron, respectively. The degradation rate of atrazine in the soil reached 67...

Solar dehydration processes, implemented with NIR sensors, were studied. The research plan was divided into phases to achieve specific objectives. Phase 1: laboratory tests on micro plants; phase 2: scale transposition tests on small-sized plants - pilot scale; phase 3: tests on commercial systems already in use by Italian SMEs. The realisation of the scheduled activities started with the design, programming, and positioning of NIR sensor for data collection and configuration optimization. NIR spectra were collected in reflectance mode (900-1700 nm) using the MicroNIR1700™ or the MicroNIR On-site W™ (VIAVI Solutions Italia S...

Cellular and molecular alterations associated with hearing loss are now better understood with advances in molecular biology. These changes indicate the participation of distinct damage and stress pathways that are unlikely to be fully addressed by conventional pharmaceutical treatment. Sensorineural hearing loss is a common and debilitating condition for which comprehensive pharmacologic intervention is not available. The complex and diverse molecular pathology that underlies hearing loss currently limits our ability to intervene with small molecules...

Natural small molecular organic matter (NSOM), ubiquitous in natural waters and distinct from humic acid or fulvic acid, is a special type of dissolved organic matter (DOM) which is characterized as strong photosensitivity and simple molecular structure. However, little study had been directed on the role of NSOM in eliminating emerging contaminants in advanced reduction process (ARP). This study took three small molecular isomeric organic acids (p-hydroxybenzoic acid, pHBA; salicylic acid, SA; m-hydroxybenzoic acid, mHBA) as the representative substances of NSOM to explore these mechanisms on promoting Ribavirin (RBV, an anti COVID-19 medicine) degradation in ultraviolet activated sulfite (UV/Sulfite) process...

Long-term visualization of changes in plasma membrane dynamics during important physiological processes can provide intuitive and reliable information in a 4D mode. However, molecular tools that can visualize plasma membranes over extended periods are lacking due to the absence of effective design rules that can specifically track plasma membrane fluorescent dye molecules over time. Using plant plasma membranes as a model, we systematically investigated the effects of different alkyl chain lengths of FMR dye molecules on their performance in imaging plasma membranes...

Ultrasmall gold nanoparticles were functionalized with peptides of two to seven amino acids that contained one cysteine molecule as anchor via a thiol-gold bond and a number of alanine residues as nonbinding amino acid. The cysteine was located either in the center of the molecule or at the end (C-terminus). For comparison, gold nanoparticles were also functionalized with cysteine alone. The particles were characterized by UV spectroscopy, differential centrifugal sedimentation (DCS), high-resolution transmission electron microscopy (HRTEM), and small-angle X-ray scattering (SAXS)...