moleculer

Amyloid plaques composed of fibrils of misfolded Aβ peptides are pathological hallmarks of Alzheimer's disease (AD). Aβ fibrils are polymorphic in their tertiary and quaternary molecular structures. This structural polymorphism may carry different pathologic potencies and can putatively contribute to clinical phenotypes of AD. Therefore, mapping of structural polymorphism of Aβ fibrils and structural evolution over time is valuable to understanding disease mechanisms. Here, we investigated how Aβ fibril structures in situ differ in Aβ plaque of different mouse models expressing familial mutations in the AβPP gene...

We propose a framework for describing the dynamics associated with the adsorption of small molecules to liquid-vapor interfaces using an intermediate resolution between traditional continuum theories that are bereft of molecular detail and molecular dynamics simulations that are replete with them. In particular, we develop an effective single particle equation of motion capable of describing the physical processes that determine thermal and mass accommodation probabilities. The effective equation is parametrized with quantities that vary through space away from the liquid-vapor interface...

Of the 27 million surgeries performed in the United States each year, a reported 2.6% result in a surgical site infection (SSI), and Staphylococci species are commonly the culprit. Alternative therapies, such as nitric oxide (NO)-releasing biomaterials, are being developed to address this issue. NO is a potent antimicrobial agent with several modes of action, including oxidative and nitrosative damage, disruption of bacterial membranes, and dispersion of biofilms. For targeted antibacterial effects, NO is delivered by exogenous donor molecules, like S -nitroso- N -acetylpenicillamine (SNAP)...

Neurogenesis involves the precisely coordinated action of genetic programs controlling large-scale neuronal fate specification down to terminal events of neuronal differentiation. The Q neuroblasts in Caenorhabditis elegans, QL on the left and QR on the right, divide, differentiate, and migrate in a similar pattern to produce three neurons each. However, QL on the left migrates posteriorly, and QR on the right migrates anteriorly. The MAB-5/Hox transcription factor is necessary and sufficient for posterior Q lineage migration and is normally expressed only in the QL lineage...

The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These tumor-host interactions are often affected by soluble bioactive molecules such as proteoglycans. Decorin, an archetypical small leucine-rich proteoglycan primarily expressed by stromal cells, affects cancer growth in its soluble form by interacting with several receptor tyrosine kinases (RTK). Overall, decorin leads to a context-dependent and protracted cessation of oncogenic RTK activity by attenuating their ability to drive a prosurvival program and to sustain a proangiogenic network...

Drug abuse is a severe social problem worldwide. Particularly, the issue of new psychoactive substances (NPSs) have increasingly emerged. NPSs are structural or functional analogs of traditional illicit drugs, such as cocaine, cannabis, and amphetamine; these molecules provide the same or more severe neurological effects. Usually, immunoassays are utilized in the preliminary screening method. However, NPSs have poor detectability in commercially available immunoassay kits. Meanwhile, various chromatography combined with the mass spectrometry platform have been developed to quantify NPSs...

Despite their widespread use as therapeutics, clinical development of small molecule drugs remains challenging. Among the many parameters that undergo optimization during the drug development process, increasing passive cell permeability (i.e., log(P)) can have some of the largest impact on potency. Cyclic peptides (CPs) have emerged as a viable alternative to small molecules, as they retain many of the advantages of small molecules (oral availability, target specificity) while being highly effective at traversing the plasma membrane...

Universal and early recognition of pathogens occurs through recognition of evolutionarily conserved pathogen associated molecular patterns (PAMPs) by innate immune receptors and the consequent secretion of cytokines and chemokines. The intrinsic complexity of innate immune signaling and associated signal transduction challenges our ability to obtain physiologically relevant, reproducible and accurate data from experimental systems. One of the reasons for the discrepancy in observed data is the choice of measurement strategy...

An amino acid-conjugated naphthalene diimide (NDI)-based highly red fluorescent radical anion has been found in a water medium under the photoradiated condition. This molecule has failed to form the radical anion in the monomeric state; however, the J aggregation in the aqueous medium has ensured the formation of radical anion in the ambient condition after the irradiation of both sunlight and UV light exposure. Electron paramagnetic resonance (EPR) studies clearly suggest the formation of radical anions. Herein, the stability of the radical anion in the aqueous medium is only a few minutes as a small amount of shaking is enough to quench the radical anion in the solution state...

The signaling molecule auxin sits at the nexus of plant biology and coordinates essentially all growth and developmental processes in plants. Auxin molecules are transported throughout plant tissues and are capable of evoking highly specific physiological responses in plant cells by inducing various molecular pathways. In many of these pathways, proteolysis plays a crucial role for correct physiological responses. This review provides a chronology of the discovery and characterisation of the auxin receptor, which is a fascinating example of separate research trajectories ultimately converging on the discovery of a core auxin signaling hub which relies on degradation of a family of transcriptional inhibitor proteins - the Aux/IAAs...

A better understanding of the aggregation states of adhesive molecules in the interfacial region with an adherend is crucial for controlling the adhesion strength and is of great inherent academic interest. The adhesion mechanism has been described through four theories: adsorption, mechanical, diffusion, and electronic. While interfacial characterization techniques have been developed to validate the aforementioned theories, that related to the electronic theory has not yet been thoroughly studied. We here directly detected the electronic interaction between a commonly used thermosetting adhesive, cured epoxy of diglycidyl ether of bisphenol A (DGEBA) and 4,4'-diaminodiphenylmethane (DDM), and copper (Cu)...

The detection and identification of nanoscale molecules are crucial, but traditional technology comes with a high cost and requires skilled operators. Solid-state nanopores are new powerful tools for discerning the three-dimensional shape and size of molecules, enabling the translation of molecular structural information into electric signals. Here, DNA molecules with different shapes were designed to explore the effects of electroosmotic forces (EOF), electrophoretic forces (EPF), and volume exclusion on electric signals within solid-state nanopores...

The bromide-chloride mixed quasi-two-dimensional (2D) perovskite, with a natural quantum well structure and tunable exciton binding energy, has gained significant attention for high-performance blue perovskite light-emitting diodes (PeLEDs). However, the relative importance of having a low trap state density or efficient exciton transfer for high-efficiency electroluminescence (EL) performance remains elusive. Here, two molecules with the benzoic acid group, sodium 4-fluorobenzoate (SFB) and 3,5-dibromobenzoic acid (DBA), are used to modulate the phase distribution and trap state to explore the effect between energy transfer and defect passivation...

The infrared beamline at BESSY II storage ring was upgraded recently to extend the capabilities of infrared microscopy. The endstations available at the beamline are now facilitating improved characterization of molecules and materials at different length scales and time resolutions. Here, the current outline of the beamline is reported and an overview of the endstations available is given. In particular, the first results obtained by using a new microscope for nano-spectroscopy that was implemented are presented...

The discovery of safe and efficient inhibitors against efflux pumps as well as metallo-β-lactamases (MBL) is one of the main challenges in the development of multidrug-resistant (MDR) reversal agents which can be utilized in the treatment of carbapenem-resistant Gram-negative bacteria. In this study, we have identified that introduction of an ethylene-linked sterically demanding group at the 3-OH position of the previously reported MDR reversal agent di-F-Q endows the resulting compounds with hereto unknown multitarget inhibitory activity against both efflux pumps and broad-spectrum β-lactamases including difficult-to-inhibit MBLs...

CD8+ T cell dysfunction impedes anti-tumor immunity in solid cancers but the underlying mechanisms are diverse and poorly understood. Extracellular matrix (ECM) composition has been linked to impaired T cell migration and enhanced tumor progression; however, impacts of individual ECM molecules on T cell function in the tumor microenvironment (TME) are only beginning to be elucidated. Upstream regulators of aberrant ECM deposition and organization in solid tumors are equally ill-defined. Therefore, we investigated how ECM composition modulates CD8+ T cell function in undifferentiated pleomorphic sarcoma (UPS), an immunologically active desmoplastic tumor...

Esophageal squamous cell carcinoma (ESCC) is the predominant form of esophageal cancer and is characterized by an unfavorable prognosis. To elucidate the distinct molecular alterations in ESCC and investigate therapeutic targets, we performed a comprehensive analysis of transcriptomic, proteomic, and phosphoproteomic data derived from 60 paired treatment-naive ESCC and adjacent non-tumor tissue samples. Additionally, we conducted a correlation analysis to describe the regulatory relationship between transcriptomic and proteomic processes, revealing alterations in key metabolic pathways...

Scientific knowledge of cancer has advanced greatly throughout the years, with most recent studies findings includes many hallmarks that capture disease's multifaceted character. One of the novel approach utilized for the delivery of anti-cancer agents includes mesenchymal stem cell mediated drug delivery. Mesenchymal stem cells (MSCs) are non-hematopoietic progenitor cells that may be extracted from bone marrow, tooth pulp, adipose tissue and placenta/umbilical cord blood dealing with adult stem cells. MSCs are mostly involved in regeneration of tissue, they have also been shown to preferentially migrate to location of several types of tumor in-vivo ...

The development of a bio-sensing strategy based on CRISPR/Cas that is exceptionally sensitive is crucial for the identification of trace molecules. Colorimetric miRNA detection utilizing CRISPR/Cas13a-triggered DNAzyme signal amplification was described in this article. The developed strategy was implemented for miRNA-21 detection as a proof of concept. The cleavage activity of Cas13a was triggered when the target molecule bonded to the Cas13a-crRNA complex and cleaved uracil ribonucleotides (rU) in the substrate probe...

This study elucidates the mass transfer mechanism of myoglobin (Mb) within a single silica particle with a 50 nm pore size at various pH levels (6.0, 6.5, 6.8, and 7.0). Investigation of Mb distribution ratio (R) and distribution kinetics was conducted using absorption microspectroscopy. The highest R was observed at pH 6.8, near the isoelectric point of Mb, as the electrostatic repulsion between Mb molecules on the silica surface decreased. The time-course absorbance of Mb in the silica particle was rigorously analyzed based on a first-order reaction, yielding the intraparticle diffusion coefficient of Mb (Dp )...