In Vitro Folliculogenesis in Mammalian Models: A Computational Biology Study

In vitro folliculogenesis (ivF) has been proposed as an emerging technology to support follicle growth and oocyte development. It holds a great deal of attraction from preserving human fertility to improving animal reproductive biotechnology. Despite the mice model, where live offspring have been achieved,in medium-sized mammals, ivF has not been validated yet. Thus, the employment of a network theory approach has been proposed for interpreting the large amount of ivF information collected to date in different mammalian models in order to identify the controllers of the in vitro system. The WoS-derived data generated a scale-free network, easily navigable including 641 nodes and 2089 links. A limited number of controllers (7.2%) are responsible for network robustness by preserving it against random damage. The network nodes were stratified in a coherent biological manner on three layers: the input was composed of systemic hormones and somatic-oocyte paracrine factors; the intermediate one recognized mainly key signaling molecules such as PI3K, KL, JAK-STAT, SMAD4, and cAMP; and the output layer molecules were related to functional ivF endpoints such as the FSH receptor and steroidogenesis. Notably, the phenotypes of knock-out mice previously developed for hub.BN indirectly corroborate their biological relevance in early folliculogenesis. Finally, taking advantage of the STRING analysis approach, further controllers belonging to the metabolic axis backbone were identified, such as mTOR/FOXO, FOXO3/SIRT1, and VEGF, which have been poorly considered in ivF to date. Overall, this in silico study identifies new metabolic sensor molecules controlling ivF serving as a basis for designing innovative diagnostic and treatment methods to preserve female fertility.

Recent Advances in Layered Double Hydroxide-Based Electrochemical and Optical Sensors

Layered double hydroxides (LDHs) have attracted considerable attention as promising materials for electrochemical and optical sensors owing to their excellent catalytic properties, facile synthesis strategies, highly tunable morphology, and versatile hosting ability. LDH-based electrochemical sensors are affordable alternatives to traditional precious-metal-based sensors, as LDHs can be synthesized from abundant inorganic precursors. LDH-modified probes can directly catalyze or host catalytic compounds that facilitate analyte redox reactions, detected as changes in the probe’s current, voltage, or resistance. The porous and lamellar structure of LDHs allows rapid analyte diffusion and abundant active sites for enhanced sensor sensitivity. LDHs can be composed of conductive materials such as reduced graphene oxide (rGO) or metal nanoparticles for improved catalytic activity and analyte selectivity. As optical sensors, LDHs provide a spacious, stable structure for synergistic guest–host interactions. LDHs can immobilize fluorophores, chemiluminescence reactants, and other spectroscopically active materials to reduce the aggregation and dissolution of the embedded sensor molecules, yielding enhanced optical responses and increased probe reusability. This review discusses standard LDH synthesis methods and overviews the different electrochemical and optical analysis techniques. Furthermore, the designs and modifications of exemplary LDHs and LDH composite materials are analyzed, focusing on the analytical performance of LDH-based sensors for key biomarkers and pollutants, including glucose, dopamine (DA), H2O2, metal ions, nitrogen-based toxins, and other organic compounds.

A Data-Driven Approach to the Development and Understanding of Chiroptical Sensors for Alcohols with Remote γ-Stereocenters

Dynamic covalent chemistry-based sensors have recently emerged as powerful tools to rapidly determine the enantiomeric excess of organic small molecules. While a bevy of sensors have been developed, those for flexible molecules with stereocenters remote to the functional group that binds the chiroptical sensor remain scarce. In this study, we develop an iterative, data-driven workflow to design and analyze a chiroptical sensor capable of assessing challenging acyclic γ-stereogenic alcohols. Fol-lowing sensor optimization, the mechanism of sensing was probed with a combination of computational parameterization of the sensor molecules, statistical modeling, and high-level density functional theory (DFT) calculations. These were used to elucidate the mechanism of stereochemical recognition and revealed that competing attractive non-covalent interactions (NCIs) determine the overall performance of the sensor. It is anticipated that the data-driven workflows developed herein will be generally applicable to the development and understanding of dynamic covalent and supramolecular sensors.

Acridino-Diaza-20-Crown-6 Ethers: New Macrocyclic Hosts for Optochemical Metal Ion Sensing

Acridino-diaza-20-crown-6 ether derivatives as new turn-on type fluorescent chemosensors with an excellent functionality and photophysical properties have been designed and synthesized for metal ion-selective optochemical sensing applications. Spectroscopic studies revealed that in an acetonitrile-based semi-aqueous medium, the sensor molecules exhibited a remarkable fluorescence enhancement with high sensitivity only toward Zn2+, Al3+ and Bi3+, among 23 different metal ions. Studies on complexation showed a great coordinating ability of logK > 4.7 with a 1:1 complex stoichiometry in each case. The detection limits were found to be from 59 nM to micromoles. The new ionophores enabled an optical response without being affected either by the pH in the range of 5.5–7.5, or the presence of various anions or competing metal ions. Varying the N-substituents of the new host-backbone provides diverse opportunities in both immobilization and practical applications without influencing the molecular recognition abilities.

Comparison in practical applications of crown ether sensor molecules containing an acridone or an acridine unit – a study on protonation and complex formation

Crown ethers containing an acridone or an acridine unit are successfully applied opto- and electrochemical cation sensors. The heteroaromatic unit of these macrocycles can be in different forms during the applications, which have a strong influence on the sensing behavior. Moreover, in the case of acridono-macrocycles a prototropic equilibrium takes place upon complexation, which is effected by the physicochemical characteristics. A Pb2+-selective acridono-18-crown-6 ether and its 9-phenylacridino-analogue were used as model compounds for comparing the different forms of the heterocyclic units of these sensor molecules. Since in most practical sensor applications of the fluorescent hosts a non-neutral aqueous medium is present, studies on complexation and signaling were carried out from the aspect of the relationship among protonation, coordinating ability, complex stability and tautomeric equilibrium. A strong interdependence among these factors was found and limitations of using unsubstituted acridino- and acridono-sensor molecules in comparison with their 9-substituted-acridino-analogues were discussed. This study will hopefully serve as a useful standpoint for future development of ionophore-based sensors containing an acridone or an acridine unit.

Signaling Through Nucleic Acid Sensors and Their Roles in Inflammatory Diseases

Recognition of pathogen-derived nucleic acids by pattern-recognition receptors (PRRs) is essential for eliciting antiviral immune responses by inducing the production of type I interferons (IFNs) and proinflammatory cytokines. Such responses are a prerequisite for mounting innate and pathogen-specific adaptive immune responses. However, host cells also use nucleic acids as carriers of genetic information, and the aberrant recognition of self-nucleic acids by PRRs is associated with the onset of autoimmune or autoinflammatory diseases. In this review, we describe the mechanisms of nucleic acid sensing by PRRs, including Toll-like receptors, RIG-I-like receptors, and DNA sensor molecules, and their signaling pathways as well as the disorders caused by uncontrolled or unnecessary activation of these PRRs.

Steric Effects on Intramolecular Charge Transfer Fluorescence of Benzo[b]thiophene-1,1-dioxide Bridged Macrocages

Intramolecular charge transfer (ICT) fluorescence has been widely investigated and exploited in sensor molecules. However, steric effects on the ICT fluorescence properties have rarely been reported so far, although research...

Fluorescence turn-off mechanism of norbornene derived homopolymer – an Al3+ colorimetric and fluorescent chemosensor

A deep understanding of fluorescence turn-off or turn-on mechanism is fundamental in designing highly effective sensor molecules. However, these mechanisms are subtle as multiple factors may affect the fluorescence signals....

Integrins, cadherins and channels in cartilage mechanotransduction: perspectives for future regeneration strategies

Articular cartilage consists of hyaline cartilage, is a major constituent of the human musculoskeletal system and has critical functions in frictionless joint movement and articular homoeostasis. Osteoarthritis (OA) is an inflammatory disease of articular cartilage, which promotes joint degeneration. Although it affects millions of people, there are no satisfying therapies that address this disease at the molecular level. Therefore, tissue regeneration approaches aim at modifying chondrocyte biology to mitigate the consequences of OA. This requires appropriate biochemical and biophysical stimulation of cells. Regarding the latter, mechanotransduction of chondrocytes and their precursor cells has become increasingly important over the last few decades. Mechanotransduction is the transformation of external biophysical stimuli into intracellular biochemical signals, involving sensor molecules at the cell surface and intracellular signalling molecules, so-called mechano-sensors and -transducers. These signalling events determine cell behaviour. Mechanotransducing ion channels and gap junctions additionally govern chondrocyte physiology. It is of great scientific and medical interest to induce a specific cell behaviour by controlling these mechanotransduction pathways and to translate this knowledge into regenerative clinical therapies. This review therefore focuses on the mechanotransduction properties of integrins, cadherins and ion channels in cartilaginous tissues to provide perspectives for cartilage regeneration.

Synthesis, Molecular Recognition Study and Liquid Membrane-Based Applications of Highly Lipophilic Enantiopure Acridino-Crown Ethers

New highly lipophilic enantiopure crown ethers containing a heterocyclic unit have been synthesized. Phase transport, UV-Vis- and fluorescence spectrophotometric investigations as well as electrochemical studies on the complexation of the new macrocycles with several amine and amino acid derivatives were also carried out. Achiral amines were used for studying the structural preference of the new macrocycles. Among the studied structural features of the guest molecules, the intermolecular π-π interaction showed the most significant effect on complexation, which made the aralkylamine-type compounds the most preferable guest molecules. The studied liquid membrane-based applications and photophysical investigations showed appreciable enantiomeric recognition toward some aralkylamine model compounds with homochiral preferences. New crown ether derivatives (R,R)-2 and (S,S)-2 were successfully applied as enantioselective carrier and sensor molecules.