Single-molecule magnets (SMMs) have garnered significant interest in the field of molecular magnetism due to their unique magnetic properties at the nanoscale. These molecular systems exhibit magnetisation behaviour reminiscent of conventional bulk magnets but with distinct advantages such as size-dependent properties and potential applications in quantum computing and high-density data storage. However, challenges remain in harnessing their properties for practical applications, including their susceptibility to degradation and limited control over their assembly and organisation.

The cornerstone of molecular magnetism is a detailed understanding of the relationship between structure and magnetic behaviour, i.e. the development of magneto-structural correlations. Traditionally, the synthetic chemist approaches this challenge by making multiple compounds that share a similar magnetic core but differ in peripheral ligation. Changes in the ligand framework induce changes in the bond angles and distances around the metal ions which are manifested in changes to magnetic susceptibility and magnetisation data. This approach requires the synthesis of series of different ligands and assumes that the chemical/electronic nature of the ligands and their coordination to the metal, the nature and number of counter ions and how they are positioned in the crystal lattice, and the molecular and crystallographic symmetry have no effect on the measured magnetic properties. In short, the assumption is that everything outwith the magnetic core is innocent, which is a huge oversimplification. The ideal scenario would be to have the same complex available in multiple structural conformations, and this is something that can be achieved through the application of external hydrostatic pressure, correlating structural changes observed through high pressure single crystal X-ray crystallography with changes observed in high pressure magnetometry, in tandem with high pressure inelastic neutron scattering (INS), high pressure electron paramagnetic resonance (EPR) spectroscopy and high pressure absorption/emission/Raman spectroscopy. In this review, which summarises our work in this area over the last 15 years, we show that the application of pressure to molecule-based magnets can (reversibly): (1) lead to changes in bond angles, distances and Jahn-Teller orientations; (2) break and form bonds; (3) induce polymerisation/depolymerisation; (4) enforce multiple phase transitions; (5) instigate piezochromism; (6) change the magnitude and sign of pairwise exchange interactions and magnetic anisotropy and (7) lead to significant increases in magnetic ordering temperatures.

The rationalization of single molecule magnets’ (SMMs) magnetic properties by quantum mechanical approaches represents a major task in the field of the Molecular Magnetism. The fundamental interpretative key of molecular magnetism is the phenomenological Spin Hamiltonian and the understanding of the role of its different terms by electronic structure calculations is expected to steer the rational design of new and more performing SMMs. This paper deals with the ab initio calculation of isotropic and anisotropic exchange contributions in the Fe(III) dimer [Fe₂(OCH₃)₂(dbm)₄]. This system represents the building block of one of the most studied Single Molecule Magnets ([Fe₄RC(CH₂O)₃)₂(dpm)₆] where R can be an aliphatic chain or a phenyl group just to name the most common functionalization groups) and its relatively reduced size allows the use of a high computational level of theory. Calculations were performed using CASSCF and NEVPT2 approaches on the X-ray geometry as assessment of the computational protocol, which has then be used to evinced the importance of the outer coordination shell nature through organic ligand modelization. Magneto-structural correlations as function of internal degrees of freedom for isotropic and anisotropic exchange contributions are also presented, outlining for the first time the extremely rapidly changing nature of the anisotropic exchange coupling.

Single particle tracking (SPT) is a powerful class of methods for studying the dynamics of biomolecules inside living cells. The techniques reveal the trajectories of individual particles, with a resolution well below the diffraction limit of light, and from them the parameters defining the motion model, such as diffusion coefficients and confinement lengths. Most existing algorithms assume these parameters are constant throughout an experiment. However, it has been demonstrated that they often vary with time as the tracked particles move through different regions in the cell or as conditions inside the cell change in response to stimuli. In this work, we propose an estimation algorithm to determine time-varying parameters of systems that discretely switch between different linear models of motion with Gaussian noise statistics, covering dynamics such as diffusion, directed motion, and Ornstein-Uhlenbeck dynamics. Our algorithm consists of three stages. In the first stage, we use a sliding window approach, combined with Expectation Maximization (EM) to determine maximum likelihood estimates of the parameters as a function of time. These results are only used to roughly estimate the number of model switches that occur in the data to guide the selection of algorithm parameters in the second stage. In the second stage, we use change detection (CD) techniques to identify where the models switch, taking advantage of the off-line nature of the analysis of SPT data to create non-causal algorithms with better precision than a purely causal approach. Finally, we apply EM to each set of data between the change points to determine final parameter estimates. We demonstrate our approach using experimental data generated in the lab under controlled conditions.

Long-read single-molecule sequencing has revolutionized de novo genome assembly and enabled the automated reconstruction of reference-quality genomes. It also has been widely used to study structural variants, phase haplotypes and more. Here, we introduce the assembler— SMARTdenovo, which is an SMS assembler that follows the overlap-layout-consensus (OLC) paradigm. SMARTdenovo (RRID: SCR_017622) was designed to be a fast assembler that did not require highly accurate raw reads for error correction, unlike other, contemporaneous SMS assemblers. It has performed well for evaluating congeneric assemblers and has been successful for a variety of assembly projects. It is compatible with Canu for assembling high-quality genomes, and several of the assembly strategies in this program have been incorporated into subsequent popular assemblers. The assembler has been in use since 2015, and here we provide information on the development of SMARTdenovo and how to implement its algorithms into current projects.

The main property of tripodal ligands is the predictable type of coordination. Homo- and heteroleptic lanthanide complexes with tripodal ligands are a representative class of compounds. However, despite the fact that many of them are paramagnetic their magnetic behavior is poorly understood. This is because their photophysical and catalytic properties have been more attractive. In the present review, we are trying to summarize the available structural information and extremely few data on magnetic properties in order to draw some conclusions about the prospective of tripods using in the design of quantum molecular magnets based on Ln ions. We would like to draw the reader's attention to the fact that despite the consideration of a large part of the currently known lanthanide compounds with tripodal ligands, this review is not exhaustive. However, our goal was to draw the attention of researchers to the fact that a whole niche of air-stable Ln complexes remained outside the attention of magnetochemists and theoreticians.

In this work we demonstrate the proof-of-concept of real-time discrimination between patches of serine or isoleucine monomers in the primary structure of custom-engineered, macro-dipole-like peptides, at uni-molecular level. We employed single-molecule recordings to examine the ionic current through the α-hemolysin (α-HL) nanopore, when hydrophilic serine or hydrophobic isoleucine residues, flanked by segments of oppositely charged arginine and glutamic amino acids functioning as a voltage-dependent ‘molecular brake’ on the peptide, were driven at controllable rates across the nanopore. The observed differences in the ionic currents blockades through the nanopore, visible at time resolutions corresponding to peptide threading through the α-HL’s constriction region, was explained by a simple model of the volumes of electrolyte excluded by either amino acid species, as groups of three serine or isoleucine monomers transiently occupy the α-HL. To provide insights into the conditions ensuring optimal throughput of peptide readout through the nanopore, we probed the sidedness-dependence of peptide association to and dissociation from the electrically and geometrically asymmetric α-HL.

Microfluidic devices have been extensively investigated in recent years in fields including ligand-binding analysis, chromatographic separation, molecular dynamics, and DNA sequencing. To prolong the observation of a single molecule in aqueous buffer, the solution in a sub-micron scale channel is driven by the electric field and reversed after a fixed delay following each passage, so that the molecule passes back and forth through the laser focus and the time before irreversible photobleaching is extended. However, this practice requires complex chemical treatment to the inner surface of the channel to prevent unexpected sticking to the surface and the confined space renders features, such as a higher viscosity and lower dielectric constant, which slow the Brownian motion of the molecule compared to the bulk liquid. In this paper, we have fixed a capillary microchannel with an inner diameter of 2 microns on top of a piezo stage to recycle the molecule and collected the fluorescence by a confocal microscope. The passing times of the molecule through the laser focus are calculated by a real-time control system based on an FPGA and the commands of translation are given to the piezo stage through a feedback algorithm. We have achieved a maximum number of recycles of more than 200 and developed a maximum-likelihood estimation of the diffusivity of the molecule, which attains results of the same magnitude as previous reports. This technique simplifies the overall procedure of the single-molecule recycling and could be useful for the ligand-binding studies of biomolecules.

HIV-1 assembly is a complex mechanism taking place at the plasma membrane of the host cell. It requires nice spatial and temporal coordination to end up with a full immature virus. Researchers have extensively studied HIV-1 assembly molecular mechanism during the past decades, in order to dissect the respective roles of viral proteins, viral genome and host cell factors. Nevertheless, the time course of the process has been observed in living cells only a decade ago. The very recent revolution of optical microscopy, combining high speed and high spatial resolution now permit to study assemblies and their consequences at the single molecule level within (living) cells. In this review, after a short description of these new approaches, we will show how HIV-1 assembly in cells has been revisited using these advanced super resolution microscopy techniques and how much it could make a bridge in studying assembly from the single molecule to the host cell.

Quantum leaps advances in the single-molecule investigative science have been made possible over the past decades through the implication of nanopores, as versatile components on dedicated biosensors. Here, we employed the nanopore-tweezing technique to capture amino acid-functionalized, peptide-nucleic acids (PNA) with -hemolysin-based nanopores, and correlate the ensuing stochastic fluctuations of the ionic current through the nanopore with the composition and order of bases in the PNAs primary structure. We demonstrate that while the system enables detection of distinct bases on homopolymeric PNA or triplet bases on heteropolymeric strands, it also reveals rich insights into the conformational dynamics of the entrapped PNA within the nanopore, relevant for perfecting the recognition capability single-molecule sequencing.

Receptor–ligand interactions at cell interfaces initiate signaling cascades essential for cellular communication and effector functions. Specifically, T cell receptor (TCR) interactions with pathogen-derived peptides presented by the major histocompatibility complex (pMHC) molecules on antigen-presenting cells are crucial for T cell activation. The binding duration, or dwell time, of TCR–pMHC interactions correlates with downstream signaling efficacy, with strong agonists exhibiting longer lifetimes compared to weak agonists. Traditional surface plasmon resonance (SPR) methods quantify 3D affinity but lack cellular context and fail to account for factors like membrane fluctuations. In the recent years, single-molecule Förster resonance energy transfer (smFRET) has been applied to measure 2D binding kinetics of TCR–pMHC interactions in a cellular context. Here, we introduce a rigorous mathematical model based on survival analysis to determine exponentially distributed receptor–ligand interaction lifetimes, verified through simulated data. Additionally, we developed a comprehensive analysis pipeline to extract interaction lifetimes from raw microscopy images, demonstrating the model’s accuracy and robustness across multiple TCR–pMHC pairs. Our new software suite automates data processing to enhance throughput and reduce bias. This methodology provides a refined tool for investigating T cell activation mechanisms, offering insights into immune response modulation.

Single-Molecule Magnets (SMMs) have attracted much interest because of their spin properties and potential technological applications. Besides, a great effort has been devoted to their functionalization, which is made with functional groups convenient to connect suitable SMMs to junction devices or to perform their grafting on surfaces of different substrates. We have synthesized and characterized two lipoic acid-functionalized and oxime-based MnIII compounds, of formula [Mn6(μ3-O)2(H2N-sao)6(lip)2(MeOH)6][Mn6(μ3-O)2(H2N-sao)6(cnph)2(MeOH)6]}·10MeOH (1) and [Mn6(μ3-O)2(H2N-sao)6(lip)2(EtOH)6]·EtOH·2H2O (2) [H2N-saoH2 = salicylamidoxime, lip = lipoate anion, cnph = 2-cyanophenolate anion]. 1 crystallizes in the triclinic system with space group Pī and 2 crystallizes in the monoclinic system with space group C2/c. In their crystal packing, adjacent Mn6 complexes are connected through non-coordinating solvent molecules, which are H-bonded to N atoms of –NH2 groups of salicylamidoxime ligand. In addition, Hirshfeld surfaces of 1 and 2 were calculated to study the variety of intermolecular interactions and different level of importance that take place in their crystal lattice, this type of computed study being the first time performed on Mn6 molecules. The study of the magnetic properties of 1 and 2 through dc magnetic susceptibility measurements reveals the coexistence of ferro- and antiferromagnetic exchange couplings between the Mn(III) metal ions in both compounds, the latter being the predominant magnetic interaction. A ground state spin value of S = 4 was obtained through isotropic simulations of the experimental magnetic susceptibility data for both 1 and 2. Ac magnetic susceptibility measurements show the occurrence of slow relaxation of the magnetization in 1 and 2, which indicate that SMM behavior take place in both compounds.

Single particle tracking is a powerful technique to investigate the motion of molecules or particles. Here we review methods for analyzing the reconstructed trajectories, step needed for deciphering the underlying mechanisms driving the motion. First, we review the traditional analysis based on the mean square displacement (MSD), highlighting sometimes-neglected factors potentially affecting results accuracy. We then report methods that exploit distributions of parameters other than displacements, e.g. angles, velocities, and times and probabilities of reaching a target, discussing how they are more sensitive in characterizing heterogeneities and transient behaviors masked in MSD analysis. Hidden Markov Models are also used for this purpose, and these allow identifying different states, their populations and the switching kinetics. Finally, we discuss a rapidly expanding field: trajectory analysis based on machine learning. Various approaches, from random forest to deep learning, are used to classify trajectory motions, which can be identified by motion models or by model-free sets of trajectory features, either previously defined or automatically identified by the algorithms. We also review free software available for some of the analysis methods. We emphasize that approaches based on combined different methods, including classical statistics and machine learning, may be the way to obtain the most informative and accurate results.

Experiments to measure a single molecule/particle, i.e. an individual molecule/particle, at room temperature or under physiological conditions without immobilization, for example on a surface, or without significant hydrodynamic flow have so far failed. This failure has given impetus to the underlying theory of Brownian molecular motion towards its stochastics due to diffusion. Quantifying the thermodynamic jitter of molecules/particles inspires many and forms the theoretical basis of single-molecule/single-particle biophysics and biochemistry. For the first time, our simulation results for a live cell (cytoplasm) show that the tracks of individual single molecules are localized in Brownian motion, while there is fanning out in fractal diffusion (anomalous diffusion).

Single molecule de novo protein sequencing based on the 'superspecificity' of amino-acyl tRNA synthetases (aaRS) is proposed. An unfolded protein molecule is threaded through a nanopore in an electrolytic cell (e-cell) to expose the terminal residue in the e-cell's trans chamber. After the residue is cleaved with an exopeptidase, a set of tRNAs, their aaRSs, and ATP are added to trans. An aaRS charges a cognate tRNA molecule with the residue. The charged tRNA (along with the other reactants) is transferred to an extended e-cell with N (20 ≤ N ≤ 61) pores in N individual cis chambers and a single trans chamber. Each pore holds an RNA molecule ending in a unique codon that is exposed in trans. The charged tRNA's anticodon base-pairs with the terminal codon of an RNA. If tRNAs and residues are fluorescently tagged with two different colors, the residue can be identified from the observed position of the resulting color pair. As charging is 'superspecific' identification is unambiguous. The protein molecule in the first e-cell is advanced by one residue and the process repeated. In this approach there is no need for precise pore current or optical intensity measurements. Potential implementation issues are discussed. Other possibilities, including one in which the terminal residue is cleaved after charging, are also examined.

Experiments to measure a single molecule/particle, i.e. an individual molecule/particle, at room temperature or under physiological conditions without immobilization, for example on a surface, or without significant hydrodynamic flow have so far failed. This failure has given impetus to the underlying theory of Brownian molecular motion towards its stochastics due to diffusion. Quantifying the thermodynamic jitter of molecules/particles inspires many and forms the theoretical basis of single-molecule/single-particle biophysics and biochemistry. For the first time, our simulation results for a live cell (cytoplasm) show that the tracks of individual single molecules are localized in Brownian motion, while there is fanning out in fractal diffusion (anomalous diffusion).

Functional dependence of the axial zero-field splitting parameter D with respect to a properly chosen geometrical parameter (Dstr) in metal complexes is termed the Magnetostructural D-Correlation. In mononuclear hexacoordinate Ni(II) complexes with the ground electronic term 3B1g (3A2g in the regular octahedron) it proceeds along two intercepting straight lines allowing to predict the sign and magnitude of the D-parameter by knowing the X-ray structure alone; Dstr is constructed from the metal-ligand bond lengths. In hexacoordinate Co(II) complexes it is applicable only in the segment of the compressed bipyramid where the ground electronic term 4B1g is orbitally non-degenerate so that the spin Hamiltonian formalism holds true. The D vs Dstr correlation is strongly non-linear and it is represented by a set of decreasing exponentials. In tetracoordinate Co(II) complexes, on the contrary, the angular distortion from the regular tetrahedron is crucial so that the appropriate structural parameter Dstr is constructed of bond angles. All of these empirical correlations originate in the electronic structure of metal complexes that can be modelled by the generalized crystal-field theory. As the barrier to spin reversal in the single-molecule magnets is proportional to the D-value, for a rational tuning and/or prediction of the single-molecule magnetic behavior knowledge/prediction of the D-parameter is beneficial. In this review, we present the statistical processing of an extensive set of structural and magnetic data of Co(II) and Ni(II) complexes, which were published over the past 15 years. Magnetostructural D-correlations defined for this data set are reviewed in detail.

There have been several developments in the field of nanopore biosensor development and sequencing applications that address previous limitations that restricted widespread nanopore use. These innovations, paired with the large-scale commercialization of biological nanopore sequencing by Oxford Nanopore Technologies, are making these platforms a mainstay in contemporary research labs. Equipped with the ability to provide long and short-read sequencing information with quick turn-around times and simple sample preparation, nanopore sequencers are quickly improving our understanding of unsolved genetic, transcriptomic, and epigenetic problems. However, there remain some key obstacles that have yet to be improved. In this review, we provide a general introduction to nanopore sequencing principles, discussing biological and solid-state nanopore developments, obstacles to single-base detection, and library preparation considerations. We conclude with examples of important clinical applications to give perspective on the potential future of nanopore sequencing in the field of molecular diagnostics.

Bloodstream infection is a major health problem worldwide, with extremely high mortality. Detecting infection in the early stage is challenging due to the extremely low concentration of bacteria in the blood. Digital PCR provides unparalleled sensitivity and can achieve absolute quantification, but it is time-consuming. Moreover, the presence of unavoidable background signals in negative controls poses a significant challenge for single-molecule detection. Here, we propose a novel strategy called “Ultrafast flexible thin tube-based droplet digital PCR (utPCR)” that can shorten the digital PCR process from 2 hours to only 5 minutes, with primer annealing/extension time reduced from minutes to only 5 seconds. Importantly, the ultrafast PCR eliminates the nonspecific amplification and thus enables single-molecular detection. The utPCR enabled sensitive detection and digital quantification of E. coli O157 in the high background of 106-fold excess of E. coli K12 cells. Moreover, this method also displayed the potential to detect rare pathogens in blood samples, and the limit of detection (LOD) could be as low as 10 CFU per mL of blood without false positive results. Considering ultrafast (<5 min) and highly sensitive (single-molecule detection), the utPCR holds excellent prospects in the next generation of molecular diagnosis.

Single-molecule fluorescence detection (SMFD) experiments are useful in distinguishing sub-populations of molecular species when measuring heterogeneous samples. One experimental platform for SMFD is based on a confocal microscope, where molecules randomly traverse an effective detection volume. The non-uniformity of the excitation profile and the random nature of Brownian motion, produce fluctuating fluorescence signals. For these signals to be distinguished from the background, burst analysis is frequently used. Yet, the relation between the results of burst analyses and the underlying information of the diffusing molecules is still obscure and requires systematic assessment. In this work we performed three-dimensional Brownian motion simulations of SMFD, and tested the positions at which molecules emitted photons that passed the burst analysis criteria for different values of burst analysis parameters. The results of this work verify which of the burst analysis parameters and experimental conditions influence both the position of molecules in space when fluorescence is detected and taken into account, and whether these bursts of photons arise purely from single molecules, or not entirely. Finally, we show, as an example, the effect of bursts that are not purely from a single molecule on the accuracy in single-molecule Förster resonance energy transfer measurements.

The nuclear lamina consists of a dense fibrous meshwork made of nuclear lamins, Type V intermediate filaments, and is ~14 nm thick according to recent cryo-electron tomography studies. Recent advances in light microscopy have extended the resolution to a scale allowing for the fine structure of the lamina to be imaged in the context of the whole nucleus. We review quantitative approaches to analyze the imaging data of the nuclear lamina as acquired by structured illumination microscopy (SIM) and single molecule localization microscopy (SMLM), as well as the requisite cell preparation techniques. In particular, we discuss the application of steerable filters and graph based methods to segment the structure of the four mammalian lamin isoforms (A, C, B1, and B2) and extract quantitative information.

Nanometer-curved surfaces are abundant in biological systems as well as in nano-sized technologies. Properly functionalized polymer-grafted nanoparticles (PGNs) adhere to surfaces with different geometries and curvatures. This work explores some of the energetic and mechanical characteristics of the adhesion of PGNs to surfaces with positive, negative and zero curvatures using Coarse-Grained Molecular Dynamics (CGMD) simulations. Our calculated free energies of binding of the PGN to the curved and flat surfaces as a function of separation distance show that curvature of the surfaces critically impacts the adhesion strength. We find that the flat surface is the most adhesive, and the concave surface is the least adhesive surface. This somewhat counterintuitive finding suggests that while a bare nanoparticle is more likely to adhere to a positively curved surface than a flat surface, grafting polymer chains to the nanoparticle surface inverts this behavior. Moreover, we studied the rheological behavior of PGN upon separation from the flat and curved surfaces under external pulling force. The results presented herein can be exploited in drug delivery and self-assembly applications.

ATTO 565, a Rhodamine-type dye, has garnered significant attention due to its remarkable optical properties, such as a high fluorescence quantum yield, it is a relatively stable structure, and has low biotoxicity. ATTO 565 has found extensive applications in combination with microscopy technology. In this review, the chemical and optical properties of ATTO 565 are introduced, along with the principles behind them. Then, the functionality of ATTO 565 in confocal microscopy, stimulated emission depletion (STED) microscopy, single-molecule tracking (SMT) techniques, and fluorescence correlation spectroscopy (FCS) is discussed. These studies demonstrate that ATTO 565 plays a crucial role in areas such as biological imaging and single-molecule localization, thus warranting further in-depth investigation. Finally, we present some prospects and concepts for the future applications of ATTO 565 in the fields of biocompatibility and metal ion detection.

Base excision repair (BER) is a cellular process that removes damaged bases arising from exogenous and endogenous sources including reactive oxygen species, alkylation agents, and ionizing radiation. BER is mediated by the actions of multiple proteins that work in a highly concerted manner to resolve DNA damage efficiently to prevent toxic repair intermediates. During the initiation of BER, the damaged base is removed by one of 11 mammalian DNA glycosylases resulting in abasic sites. Many DNA glycosylases are product inhibited by binding to the abasic site more avidly than the damaged base. Traditionally apurinic/apyrimidinic endonuclease, APE1, was believed to help turnover the glycosylases to undergo multiple rounds of damaged base removal. However, in a series of papers from our laboratory we have demonstrated that UV-damaged DNA binding protein (UV-DDB) stimulates the glycosylase activities of human 8-oxoguanine glycosylase (OGG1), MUTY DNA glycosylase (MUTYH), alkyladenine glycosylase/N-methylpurine DNA glycosylase (AAG/MPG), and single-strand selective monofunctional glycosylase (SMUG1), between three-to-five-fold. Moreover, we have shown UV-DDB can assist chromatin decompaction facilitating access of OGG1 to 8-oxoguanine damage in telomeres. This review summarizes the biochemistry, single-molecule, and cell biology approaches that our group used to directly demonstrate the essential role of UV-DDB in BER.

Biological systems are highly regulated. They are also highly resistant to sudden perturbations enabling them to maintain the dynamic equilibrium essential for sustenance of life. This robustness is conferred by regulatory mechanisms that influence the activity of enzymes/proteins within their cellular context, to adapt to changing environmental conditions. However, the initial rules governing the study of enzyme kinetics were tested and implemented for mostly cytosolic enzyme systems that were easy to isolate and/or recombinantly express. Moreover, these enzymes lacked complex regulatory modalities. Now, with academic labs and pharmaceutical companies turning their attention to more complex systems (for instance, multi-protein complexes, oligomeric assemblies, membrane proteins and post-translationally modified proteins), the initial axioms defined by Michaelis-Menten (MM) kinetics are rendered inadequate and the development of a new kind of kinetic analysis to study these systems is required. The current review strives to present an overview of enzyme kinetic mechanisms that are atypical and, oftentimes, do not conform to the classical MM kinetics. Further, it presents initial ideas on the design and analysis of experiments in early drug-discovery for such systems, to enable effective screening and characterisation of small-molecule inhibitors with desirable physiological outcomes.

Comparing to males, females require much more morphine to produce comparable levels of analgesia, suggesting a difference in the endogenous hyperalgesia and analgesia modulation between sexes. Aside from hormones, emerging evidence suggests sex-differential intrinsic neural regulation of pain generation and maintenance. According to the International Association for the Study of Pain (IASP) and American College of Gastroenterology (ACG), up to 25 % of the population having visceral pain at any one time, and in the United States 10-15 percent of adults suffering from irritable bowel syndrome (IBS). Here we analyzed literatures on clinical reports of sex differences in visceral pain focusing on IBS, other form of bowel dysfunction and comorbidities, and summarized animal models that provided means to investigate the underlying molecular mechanisms in sexual dimorphism of visceral pain. Neurons and nonneuronal cells (glia and immune cells) in the peripheral and central nervous systems all contribute to sex-dependent nociception and nociplasticity in the painful signal processing. Emotion is another factor in pain perception and appears to have sexual dimorphism.

Yellow fever (YF) is a pansystemic disease caused by the yellow fever virus (YFV), the prototype species of the family Flaviviridae and genus Flavivirus, and has a highly complex host-pathogen relationship, in which endothelial dysfunction reflects viral disease tropism. In this study, the in situ endothelial response was evaluated. Liver tissue samples were collected from 21 YFV-positive patients who died due to the disease and five flavivirus-negative controls who died of other causes and whose hepatic parenchyma architecture was preserved. Immunohistochemical analysis of tissues in the hepatic parenchyma of YF cases showed significantly higher expression of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and very late antigen-4 in YFV-positive cases than in flavivirus-negative controls. These results indicate that endothelium activation aggravates the inflammatory response by inducing the expression of adhesion molecules that contribute to the rolling, recruitment, migration, and construction of the inflammatory process in the hepatic parenchyma in fatal YF cases.

A growing body of research aims at solving what is often referred to as the stimulus-percept problem in olfactory perception. Although computational efforts have made it possible to predict perceptual impressions from the physicochemical space of odors, studies with large psychophysical data sets from non-experts remain scarce. Following previous approaches, we developed a physicochemical odor space using 4,094 molecular descriptors of 1,389 odor molecules. For 20 of these odors, we examined associations with perceived pleasantness, intensity, odor quality and detection threshold, obtained from a dataset of 2,000 naïve participants. Our results show significant differences in perceptual ratings, and we were able to replicate previous findings on the association between perceptual ratings and the first dimensions of the physicochemical odor space. However, the present analyses also revealed striking interindividual variations in perceived pleasantness and intensity. Additionally, interactions between pleasantness, intensity, and olfactory and trigeminal qualitative dimensions were found. Our results support previous findings on the relation between structure and perception on the group level in our sample of non-expert raters. Nevertheless, human olfactory perception is no analytic process of molecule detection alone. Therefore, to gain an understanding of stimulus-percept relationship in the individual, future studies should shift towards a more holistic view that takes into account the influences of context, experience and other interpersonal characteristics.

Biological parameters extracted from electrical signals from various body parts have been used for many years to analyze the human body and its behavior. In addition, electrical signals from cancer cell lines, normal cells, and viruses, among others, have been widely used for the detection of various diseases. Single-cell parameters such as cell and cytoplasmic conductivity, relaxation frequency, and membrane capacitance are important. There are many techniques available to characterize biomaterials, such as scanning tunneling microscopy (STM), nanotechnology, microstrip cavity resonance measurement, dielectric impedance measurement (DEPIM), etc. This article reviews the single cell isolation and sorting techniques, summarizes the common single cell operations such as impedance flow cytometry, cell electrical impedance, electrical impedance sensing, and summarizes the current single cell analysis techniques and their applications.

Ribosome assembly is one of the most fundamental processes in gene expression and has served as a playground to investigate the molecular mechanisms of how protein-RNA complexes (RNPs) assemble. The bacterial ribosome is composed of around 50 ribosomal proteins several of which are co-transcriptionally assembled on a ~4,500 nucleotides long pre-rRNA transcript that is further processed and modified during transcription, the entire process taking around 2 minutes in vivo and assisted by dozens of assembly factors. How this complex molecular process works so efficiently to produce an active ribosome has been investigated over decades and has resulted in the development of a plethora of novel approaches that can also be used to study the assembly of other RNPs. Here we review biochemical, structural and biophysical methods that have been developed and integrated to provide a detailed and quantitative understanding of this complex and intricate molecular process of assembly. We also discuss emerging cutting-edge approaches that could be used in the future to study how transcription, rRNA processing, cellular factors and the native cellular environment shape ribosome assembly and RNP assembly at large.

Small molecule kinase inhibitors (SMKIs) are one of the heightened concerns in the field of drug research and development. There are seventy-nine (up to July 2023) small molecule kinase inhibitors have been approved by FDA and hundreds kinase inhibitors candidates in clinical trials, which shed light on the treatment of some major diseases. As an important strategy of drug design, computer-aided drug design (CADD) plays an indispensable role in the discovery of SMKIs. CADD methods, such as docking, molecular dynamic, pharmacophore have been applied to the design and optimization of small molecule kinase inhibitors. In the review, we provide an overview of recent advances in CADD and SMKIs; and the application of CADD for discovery of SMKIs.

The poor water-solubility and instability of Ru(II) carbonyl complex hamper the therapeutic application as CO releasing materials (CO-RMs). To enhance the hydrophilicity and bio-utility of CO, a robust Ru(I) carbonyl sawhorse skeleton were grafted with water-soluble PEGlyated sidearms. Twelve PEGlyted sawhorse Ru2(CO)4 complexes were prepared with satisfactory yields and characterized by IR and 1H- and 13C- NMR. X-ray diffraction analysis of CO-RM 8, 13 and 14 revealed the featured diruthenium sawhorse skeleton and PEGylated axial ligands. The flask-shaking method measures the hydrophilicity of CO-RMs, indicating that both bridging carboxylate ligand and PEGlyated axial ligands regulate the hydrophilicity of these CO-RMs. Under photolysis conditions, CO-RM 4-13 sustainable released therapeutic amounts of CO in myoglobin assay. The correlation of the CO release kinetics and hydrophilicity of CO-RMs demonstrated that the more hydrophilic CO-RM released CO faster. The biological test found the low cytotoxic CO-RM 4 showed a specific anticancer activity toward HT-29 tumour cells.

Aminoacyl-tRNA synthetases (ARSs) are essential enzymes for translating amino acids for protein synthesis. Their function in pathogen-derived infectious diseases has been well established, which has led to development of small molecule therapeutics. The applicability of ARS inhibitors for other human diseases such as fibrosis has recently been explored in the clinical setting. There are active studies to find small molecule therapeutics for cancers. Studies on central nervous system (CNS) disorders are burgeoning as well. In this regard, we present a concise analysis of the recent development of ARS inhibitors based on small molecules from the discovery research stage to clinical studies as well as a recent patent analysis from the medicinal chemistry point of view.

We consider the problem of scheduling tasks on a single machine subject to an uncertain breakdown to minimize the flowtime. Assume the machine is unavailable during the breakdown; the starting time of the breakdown is a random variable s with distribution function D(s) and the terminating time of the breakdown has no any other information; jobs are non-resumable. Under the assumptions, starting from the perspective of statistical optimization, we first define the expected competitive ratio of an algorithm to find the optimized solution with the considered problem. Further, we propose and prove a certain result on the expected competitive ratio of the SPT rule. In particular, we show that under a quite loose condition the expected competitive ratio of the SPT rule is no more than 5/4. Meanwhile, we also make some discussions about our studies. What we have done will rich and improve the studying results on the area of scheduling to minimize flowtime and advance the development of online optimization and statistical optimization.

The microspheres constituted by proteinoids synthesized from Fox’s simulation experiments. They had peptide bond structure and weak catalysis, as well as proliferated themselves. Such microspheres were believed the models for primitive life. Due to lack of metabolism and self-reproduction, the microspheres could not meet requirements of life. Thus, how microspheres could evolved into primitive life remain unsolved mysteries. The microspheres were supposed a dissipative structure and the processes of absorption and hydrolysis could be balanced to maintain their stability by consuming proteinoid. Proteinoid molecules differed in their life spans, which were mainly determined by their multi-space structures. Consequently, molecule selection and retention could occur spontaneously in microspheres and lead to a more organized and stabilized structure of the whole microsphere with time through dissipative process. More complex chain network of chemical reactions could happen in microspheres because the proteinoid with complex, ordered multi-space structure and relatively high catalytic activity would retain. In such microspheres, nucleotides could produce and further aggregate into RNA. The synthesis of real proteins could take place with RNA as the template catalyzed by proteinoids or RNA inside microspheres. When template-based protein molecules replaced the proteinoid inside the microspheres, a protein-based self-catalyzed network of chemical reactions could take place. It is plausible if Fox’s proteinoids microspheres is to dawn on a dissipative structure, then molecule selection could occur spontaneously by “dissipative” proteinoids, and the microspheres would acquire catalytic activity due to preserved the proteinoid with a large molecular weight and relatively complex and ordered multi-space structure, and relatively high catalytic activity. Thus the microspheres would spontaneously go to self-organizing, and evolve into primitive life.

Background: Biological processes are based on complex networks of cells and molecules. Single cell multi-OMICs is a new tool aiming to provide new incites in the complex network of events controlling the functionality of the cell.; Methods: Since single cell technologies provide many sample measurements, they are the ideal environment for the application of deep learning and machine learning approaches. An autoencoder (AE) is composed of an encoder and a decoder sub-model. AE are very powerful in data compression and noise removal. However, the decoder model remains a black box from which is impossible to depict the contribution of the single input elements. We have recently developed a new class of autoencoders, called Sparsely Connected Autoencoders (SCA), which have the advantage of providing a controlled association among the input layer and the decoder module. This new architecture has the benefit that the decoder model is no anymore a black box and it can be used to depict new biologically interesting features from single cell data; Results: In this paper, we show that SCA hidden layer can grab new information usually hidden in single cell data, like as providing clustering on meta-features difficult, i.e. transcription factors expression, or impossible, miRNA expression, to depict in single cell RNAseq data. Furthermore, a SCA representation of cell clusters has the advantage of simulating a conventional bulk RNAseq, which is a data transformation allowing the identification of similarity among independent experiments; Conclusions: In our opinion, SCA represent the bioinformatics version of a “Swiss Army knife” for the extraction of hidden knowledgeable features from single cell OMICs data.

Although early work on parental burnout in the 1980s did not link parental burnout to specific parenting situations, the idea that parents affected by specific vulnerability factors were particularly at risk of burnout quickly emerged. Based on the etiological model of parental burnout (i.e., the balance between risks and resources), the objective of this study was to determine if there were specific vulnerability factors that significantly increase the risk of parental burnout. 2,563 parents participated in the study. We compared parents with a child with special needs (n = 25), parents who had adopted a child (n = 130), and single parents (n = 109), to strictly matched control groups of parents. Parents with a child with special needs displayed higher burnout and lower balance between risk and resources than the control group; parents with an adopted child had similar levels of both parental burnout and balance; and single parents had higher parental burnout but similar balance. Parents who combined specific several vulnerability factors were at greater risk of burnout. Single parenthood and adoption do not in themselves trigger a process leading de facto to other risk factors, but having a child with special needs does.

The beta-galactoside-binding mammalian lectin galectin-1 can bind, via its carbohydrate recognition domain (CRD), various cell surface glycoproteins and has been implicated in a range of cancers. As a consequence of binding to sugar residues on cell surface receptors it has been shown to have a pleiotropic effect across many cell types and mechanisms resulting in immune system modulation and cancer progression. As a result, it has started to become a therapeutic target for both small and large molecules. In previous studies, we have used fluorescence polarisation (FP) assays to determine KD values to screen and triage small molecule glycomimetics that bind to the galectin-1 CRD. In this study surface plasmon resonance (SPR) was used to compare human and mouse galectin-1 affinity measures with FP as SPR has not been applied for compound screening against this galectin. Binding affinities for a selection of mono- and di-saccharides covering a 1,000-fold range correlated well between FP and SPR assay formats for both human and mouse galectin-1. It was shown that slower dissociation drove the increased affinity at human galectin-1 whilst faster association was responsible for the effects at mouse galectin-1. This study demonstrates that SPR is a sound alternative to FP for early drug discovery screening and determining affinity estimates. Consequently, it also allows association and dissociation constants to be measured in a high throughput manner for small molecule galectin-1 inhibitors.

Advanced glycation end products (AGEs) play a significant role in the aging processes, further regarding as a hallmark of aging. Despite the importance, a lack of monitoring tools has hampered the study of relationship between AGEs and aging. Here, we firstly report a novel AGEs-selective probe, AGO. AGO presented its ability to detect AGEs more sensitively than a conventional approach of measuring autofluorescence from AGEs. In addition, we confirmed that AGO can detect AGEs depending on kinetics, reflecting by a preference to ribose-derived AGEs. Finally, AGO revealed its competence to visualize glycation products in glycation mimicking model, made by collagen framework. We believe that this study will enrich molecular toolboxes to understand physiological processes of AGEs during aging processes.

The glycosaminoglycan, heparan sulphate (HS), orchestrates many developmental processes. Yet its biological role has not yet fully been elucidated. Small molecule chemical inhibitors can be used to perturb HS function and these compounds pro-vide cheap alternatives to genetic manipulation methods. However, existing chemical inhibition methods for HS also interfere with chondroitin sulphate (CS), complicating data interpretation of HS function. Herein, a simple method for the selective inhibition of HS biosynthesis is described. Using endogenous metabolic sugar pathways, Ac4GalNAz produces UDP-GlcNAz, which can target HS synthesis. Cell treatment with Ac4GalNAz resulted in defective chain elongation of the polymer and decreased HS expression. Conversely, no adverse effect on CS production was observed. The inhibition was transient and dose-dependent, affording rescue of HS expression after removal of the unnatural azido sugar. The utility of inhibition is demonstrated in cell culture and in whole or-ganisms, demonstrating that this small molecule can be used as a tool for HS inhibition in biological systems.

The folding of certain proteins (e.g., enzymes) into perfectly defined 3D conformations via multi-orthogonal interactions is critical to their function. Concerning synthetic polymers chains, the “folding” of individual polymer chains at high dilution via intra-chain interactions leads to so-called single-chain nanoparticles (SCNPs). This review article describes the advances carried out in recent years in the folding of single polymer chains into discrete SCNPs via multi-orthogonal interactions using different reactive chemical species where intra-chain bonding only occurs between groups of the same species. First, we summarize results from computer simulations of multi-orthogonally folded SCNPs. Next, we comprehensively review multi-orthogonally folded SCNPs synthesized via either non-covalent bonds or covalent interactions. Finally, we conclude by summarizing recent research about multi-orthogonally folded SCNPs prepared through both reversible (dynamic) and permanent bonds.

ACE2, the putative receptor for the novel coronavirus (2019-nCoV), played an important role in cell entry of 2019-nCoV. However, it is not yet clear what cell types within the human body express ACE2. Here, a systematic analysis was undertaken using published single cell datasets. In total, our study analyzed 229652 cells, from five different organs, derived from 88 donors. The top ACE2 expressing cells include proximal tubule cells in the kidney and enterocytes in the intestine. Other major ACE2 expressing cells in the kidney include podocytes, intercalated cells and endothelial cells. Our results offer a comprehensive atlas of ACE2 expression at the single cell level and unravel the enormous potential targets of 2019-nCoVinfection beyond the lung.

Clean use of photons from light to activate chemical reactions offer many possibilities in different fields, from chemistry and biology to materials science and medicine. This review article describes the advances carried out in last decades toward the phototriggered synthesis of single-chain polymer nanoparticles (SCNPs) as soft nanomaterials with promising applications in enzyme-mimicking catalysis and nanomedicine, among other different uses. First, we summarize different strategies developed to synthesize SCNPs based on photoactivated intrachain homocoupling, phototriggered intrachain heterocoupling and photogenerated collapse induced by external cross-linker. Next, we comprehensively review the emergent topic of photoactivated multifolding applied to SCNP construction. Finally, we conclude by summarizing recent strategies towards phototriggered disassembly of SCNPs.

Amino acid sequences of native proteins are generally not palindromic. The protein molecule obtained as a result of reading the amino acid sequence backwards, i.e., a retro-protein, having the same amino acid composition and the same hydrophobicity profile as the native sequence may behave as a different molecule. Here we have used R4, a directed evolution product of Scfv-13, a protein that binds β-galactosidase, and report the properties of the retro-R4 (rR4). rR4 remains a binding protein and its new target is Glutamine-fructose-6-phosphate aminotransferase (GLMS), a native E. coli protein. Additionally, a tight junction immunoglobulin domain- containing membrane protein, junctional adhesion molecule A (JAMA) retro-protein retains the ability to drive cell-cell interactions. Thus, protein engineering suggests a new potential application to retro-proteins of the immunoglobulin superfamily.

Soluble cell adhesion molecules (sCAMs) are secreted ectodomain fragments of surface adhesion molecules, ICAM1 and VCAM1. sCAMs have diverse immune functions beyond their primary function, impacting immune cell recruitment and activation. Elevated sVCAM1 levels have been associated with poor cardiovascular disease (CVD) outcomes, supporting its role as a potential diagnostic marker and therapeutic target. Inhibiting sVCAM1 release or interaction with immune cells could offer cardioprotection in conditions such as diabetes. Membrane bound surface adhesion molecules are widely expressed in a wide variety of cell types with higher expression in endothelial cells (ECs), but the source of sCAMs in the circulation is not clear. Hypothesizing that endothelial cells (ECs) could be a potential source of sCAMs, this study investigated whether dysfunctional EC signaling mechanisms during diabetes cause VCAM1 ectodomain shedding. Our results from samples from a inducible diabetic mouse model revealed increased sVCAM1 plasma levels in diabetes. Protein analysis indicated upregulated VCAM1 expression and metalloproteases ADAM10 and ADAM17 in diabetic ECs. ADAMs are known for proteolytic cleavage of adhesion molecules, contributing to inflammation. GSK3β, implicated in EC VCAM1 expression, was found to be activated in diabetic ECs. GSK3β overexpression in control ECs increased ADAM10/17 and VCAM1. A GSK3β inhibitor reduced active GSK3β and VCAM1 ectodomain shedding. These findings suggest that diabetic ECs with elevated GSK3β activity led to VCAM1 upregulation and ADAM10/17-mediated sVCAM1 shedding. This mechanism underscores the potential therapeutic role of GSK3β inhibition in reducing the levels of circulating sVCAM1. The complex roles of sCAMs extend well beyond CVD. Thus, unraveling the intricate involvement of sCAMs in the initiation and progression of vascular disease particularly in diabetes, holds significant therapeutic potential.

Plant roots host various microorganisms around and inside their roots, known as the root microbiome. To become healthy and productive, plants should keep under surveillance niches around the roots to recognize disease-causing microbes and similarly exploit the services of beneficial microorganisms in nutrient acquisition, stress mitigation and growth promotion. Here we presented the communication strategies between plant roots and root-associated microbes in improving plant growth and yield. Understanding how plant root and root-associated microbes communicate is vital in designing ecofriendly strategies for targeted disease suppression and improved plant growth that will help in sustainable agriculture.

Resolving small molecule mixtures by nuclear magnetic resonance (NMR) spectroscopy has been of great interest for a long time for its precision, reproducibility and efficiency. However, spectral analyses for such mixtures are often highly challenging due to overlapping resonance lines and limited chemical shift windows. The existing experimental and theoretical methods to produce shift NMR spectra in dealing with the problem have limited applicability owing to sensitivity issues, inconsistency and / or requirement of prior knowledge. Recently, we have resolved the problem by decoupling multiplet structures in NMR spectra by the wavelet packet transform (WPT) technique. In this work, we developed a scheme for deploying the method in generating highly resolved WPT NMR spectra and predicting the composition of the corresponding molecular mixtures from their 1H NMR spectra in an automated fashion. The four-step spectral analysis scheme consists of calculating WPT spectrum, peak matching with a WPT shift NMR library, followed by two optimization steps in producing the predicted molecular composition of a mixture. The robustness of the method was tested on an augmented dataset of 1000 molecular mixtures, each containing 3 to 7 molecules. The method successfully predicted the constituent molecules with a median true positive rate of 1.0 against the varying compositions, while a median false positive rate of 0.04 was obtained. The approach can be scaled easily for much larger datasets.

Ramsey theory influences the dynamics of mechanical systems, which may be described as abstract complete graphs. We address a mechanical system which is completely interconnected with the two kinds of ideal Hookean springs. The suggested system mechanically corresponds to the cyclic molecules, in which functional groups are interconnected with two kinds of chemical bonds, represented mechanically with two springs k1 and k2. In this paper, we consider a Cyclic system (molecule) built of six equal masses m and two kinds of springs. We pose the following question: what is the minimal number of masses in the such a system in which three masses are constrained to be connected with spring k1 or three masses to be connected with spring k2? The answer to this question is supplied by the Ramsey theory, and it is formally stated as follows: what is the minimal number R3,3? The result emerging from the Ramsey theory is R3,3=6. Thus, in the aforementioned interconnected mechanical system will be necessarily present the triangles (at least one triangle), built of masses and springs. This prediction constitutes the vibrational spectrum of the system. Thus, the Ramsey Theory supplies the selection rules for the vibrational spectra of the cyclic molecules. Symmetrical system built of six vibrating entities is addressed. The Ramsey approach works for 2D and 3D molecules, which may be described as abstract complete graphs. The extension of the proposed Ramsey approach to the systems, partially connected by ideal springs, viscoelastic systems and systems, in which elasticity is of an entropy nature is discussed. “Multi-color systems” built of three kinds of ideal springs are addressed. The notion of the inverse Ramsey network is introduced and analyzed.

HIV-1 Tat protein interacts with TAR RNA and recruits CDK9/cyclin T1 and other host factors to induce HIV-1 transcription. Thus Tat-TAR RNA interaction, which is unique for HIV-1, represents an attractive target for anti-HIV-1 therapeutics. To target Tat-TAR RNA interaction, we used a crystal structure of TAR RNA with acetylpromazine bound to the bulge of TAR RNA, to dock compounds from Enamine database containing 1.6 million individual compounds. Docking identified 173 compounds that were analyzed for the inhibition of HIV-1 infection. Top ten inhibitory compounds with IC50 ≤ 6 µM were selected and the three least toxic compounds, T6780107 (IC50=2.97 μM), T0516-4834 (IC50=0.2 μM) and T5628834 (IC50=3.46 μM), were further tested for HIV-1 transcription inhibition. Only T0516-4834 compound showed selective inhibition of Tat-induced HIV-1 transcription, whereas T6780107 compound inhibited equally basal and Tat-induced transcription and T5628834 compound only inhibited basal HIV-1 transcription. The T0516-4834 compound also showed strongest inhibition of HIV-1 gag RNA expression and p24 production in CEM T cells infected with HIV-1 IIIB. Of the three compounds, only the T0516-4834 compound disrupted Tat-TAR RNA interaction indicating that it might target TAR RNA. Also, of the three tested compounds, T5628834 but not T6780107 or T0516-4834 disrupted Tat-CDK9/cyclin T1 interaction. Taken together, our study identified novel compound T0516-4834 that disrupted Tat-TAR RNA interaction and inhibited Tat-induced transcription and HIV-1 infection suggesting that this compound might serve as a new lead for anti-HIV-1 therapeutics.

Nisin, an antibacterial compound produced by Lactococcus lactis strains, has been approved by the US Food and Drug Administration to be used as a safe food additive to control the growth of undesirable pathogenic bacteria. Nisin is commonly described as a pH-dependent primary metabolite, since its production depends on growth and culture pH evolution. However, the relationship between bacteriocin synthesis and the consumption of the limiting nutrient has not been described until now. Therefore, this study aimed to develop a competitive four-dimensional Lotka Volterra-like equation to describe the relationships between culture pH, limiting nutrient (total nitrogen: TN) consumption and production of biomass (X) and nisin (BT) in four series of batch fermentation with L. lactis CECT 539 in diluted whey (DW)-based media. The developed four-dimensional LV-like equation (with a unique set of parameters) could not be used to describe all cultures belonging to each fermentation series. However, the four-dimensional LV-like equation described accurately each individual culture, providing a good description of the relationships between pH, TN, X and BT, higher values for R2 and F-ratios, lower values (&lt; 10%) for the mean relative percentage deviation modulus, with bias and accuracy factor values approximately equal to one.

Drug design is used for different applications of bioinformatics tools analyze DNA, genome, and sequence target region of a small organic molecule in order to understand the molecules of disease. Bioinformatics tools are identified a newly wide research field and minimize future risks through web servers and data mining. Clinical sample test performed with the bioinformatics tools as the biomedical detective. A particular structure and configuration of protein obliging in Drug design concluded Bioinformatics. This review bioinformatics tools and webserver will discuss functions of small organic molecules according to clinical pharmacology.

Filamentous fungi such as Aspergillus spp. are opportunistic pathogens, which cause highly invasive infections, especially in immunocompromised individuals. Control of such fungal pathogens is increasingly problematic due to the small number of effective drugs available for treatment. Moreover, the increased incidence of fungal resistance to antifungal agents makes this problem a global human health issue. The cell wall integrity system of fungi is the target of antimycotic drugs echinocandins, such as caspofungin (CAS). However, echinocandins cannot completely inhibit the growth of filamentous fungal pathogens, which results in survival/escape of fungi during treatment. Chemosensitization was developed as an alternative intervention strategy, where co-application of CAS with the intervention catalyst octyl gallate (OG; chemosensitizer) greatly enhanced CAS efficacy, thus achieved ≥ 99.9% elimination of filamentous fungi in vitro. Based on hypersensitive responses of Aspergillus antioxidant mutants to OG, it is hypothesized that, besides destabilizing cell wall integrity, the redox-active characteristic of OG may further debilitate fungal antioxidant system.

p-Hydroxyphenylpyruvate dioxygenase (HPPD) is not only the useful molecular target in treating life-threatening tyrosinemia type I, but also an important target for chemical herbicides. A combined in silico structure-based pharmacophore and molecular docking based virtual screening were performed to identify novel potential HPPD inhibitors. The complex based pharmacophore model (CBP) with 0.721 of ROC used for screening compound showed remarkable ability to retrieve known active ligands from decoy molecule. The ChemDiv database was screened using CBP-Hypo2 as a 3D query, and the best-fit hits subjected to molecular docking with two methods of LibDock and CDOCKER in Accelrys Discovery Studio 2.5(DS 2.5) to discern interactions with key residues at the active site of HPPD. 4 Compounds with top rank in HipHop model and well-known binding model were finally chosen as identification of lead compounds with potentially inhibitory effects on active site of target. The results provided powerful insight to the development of novel HPPD inhibitors herbicides using computational techniques.

The application of hydrogen flooding was recently shown to be a simple and effective approach towards improved layer differentiation and interface determination during SIMS depth profiling of thin films as well as an approach with a potential in the field of quantitative SIMS analyses. To further study the effects of hydrogen, the flooding of H₂ molecules was compared to the reactions of the atomic H on the samples of pure metals and their alloys. H₂ was introduced into the analytical chamber via a capillary which was, to achieve the dissociation, heated to approximately 2200 K. Dissociation of H₂ up to 30% resulted in a significant increase in the intensity of the metal hydride cluster secondary ions originating from the metallic samples. Comparison of time scales of possible processes provided an insight into the mechanism of the hydride cluster secondary ion formation. Cluster ions presumably form during the recombination of the atoms and molecules from the sample and adsorbed atoms and molecules from the gas. This process occurs on the surface or just above it during the sputtering process. These findings coincide with the previous mechanistic and computational studies.

The effect of doublet state metalloradical complex in a solar cell inside the common active layer poly(3-hexylthiophene)/ [6,6]-phenyl-C61-butyric acid methyl ester (P3HT/PC60BM) is explored. In this work is demonstrated that the role of the Bis-[1,3-Bis-(2,6-diisopropylphenyl)-4,5-dichloroimidazol-2-ylidene]palladium(I) hexafluoridophosphate dopant, [Pd(IPrCl)2][PF6], is crucial because, by having a stable unpaired electron in the molecule, it significantly improves the optoelectronic performance of the devices. We found the optimal concentration of this molecule in the active layer, and we demonstrated that the presence of this additive in the active layer helps to significantly improve the morphology of the device. The improvements in optoelectronic and morphological parameters are associated with a remarkable increase of photocurrent generation due to more favourable mechanisms of charge separation at the donor/acceptor (D/A) interfaces of the active layer and reduced recombinations. Moreover, the presence of this additive improves the stability of the unencapsulated solar cell against photochemical degradation produced by sunlight.

Ab initio density functional theory molecular dynamics extensive calculations were used for the first time to evaluate stability conditions for relevant phases of InN. In particular, thermal decomposition of InN with formation of N2 molecules and pressure induced wurtzite – rocksalt solid-solid phase transition were established. The results consistent with available experimental data allowed a critical evaluation of potential and limitations of the proposed simulation method. The ab initio molecular dynamics as an efficient tool for simulations of phase transformations of InN including solid-solid structural transition and thermal decomposition with formation of N2 molecules has been demonstrated. It is of high interest because InN being important component of epitaxial quantum structures has still not been obtained as a bulk single crystal making difficult a determination of its basic physical properties and designing new applications.

Optical beam splitter is used for dividing an input optical beam into several separate beams with specific power ratio. Usually, conventional beam splitters have bulky dimensions and fixed dividing ratio which significantly limit the design of new miniaturized optical devices and integrated optical circuits. We propose and investigate a novel physical concept of a miniaturized planar optical splitter/coupler with a switching element in the form of a photonic molecule (PM) pair dispersing input optical fluxes along multiple ways with variable power proportions. The structural design of the proposed splitter is based on a silicon-on-insulator (SOI) platform and composed of high-quality resonators in the form of electromagnetically coupled submicron-sized microcylinders. The control on the power division ratio and the selection of optical beam directions is realized by tuning the photonic splitter structure to the corresponding resonance of PM supermode. Compared to known analogues, the proposed design is easy to fabricate, suitable for integration into a "System-on-a-chip" platform and can dynamically change the beam power division ratio by input wave-phase manipulation.

The purpose of this study was to determine the effects of aerobic exercise on carotid to femoral pulse wave velocity (cf-PWV), cell adhesion molecules (intracellular adhesion molecules (ICAM-1), vascular cell adhesion molecules (VCAM-1), and endothelial selectin (E-selectin), and oxidized-LDL in elderly women aged 70–85 years, and to identify the effect of and correlation with vascular stiffness. Forty participants were recruited and divided into three groups; vascular stiffness (VSG, n=14), obesity (OG, n=14), and normal (NG, n=12). All groups were given a 16-week intervention of aerobic exercise, and the data collected before and after exercise were analyzed using SPSS Ver. 23.0. Two-way repeated-measures ANOVA was used to evaluate between-group and time-dependent interaction effects. One-way ANOVA was used to evaluate between-group variations. In addition, the significance was tested using a post-hoc test (Scheffe). The within-group variations by time before and after exercise were examined using a paired t-test, and correlation analysis was performed using Pearson correlation coefficients. Simple regression analysis was performed for variables showing significant differences. The results indicated interaction effects for cf-PWV (p<.001), VCAM-1 (p<.01), E-selectin (p<.05) and oxidized LDL (p<.001). The rate of change of cf-PWV was positively correlated with that of VCAM-1 (r=.352, p<.05) and that of oxidized-LDL (r=.325, p<.05) with statistical significance. To determine the effect of the rate of change of cf-PWV on the rate of change of VCAM-1, the variables were tested, and the coefficient of determination in the regression analysis was .124, indicating that 12.4% of the tested variables fit the standard regression line. The variables for the effect of the rate of change of cf-PWV on the rate of change of oxidized LDL were also tested, and the coefficient of determination in the regression analysis was .106, indicating that 10.6% of the tested variables fit the standard regression line. Thus, the 16-week regular and consistent aerobic exercise program had significant effects on the cf-PWV, ICAM-1, VCAM-1, E-selectin, and oxidized-LDL in elderly Korean women with vascular stiffness, suggesting improvements in vascular stiffness, based on which the intervention is predicted to contribute to the prevention of vascular dysfunction by lowering the risk of cardiovascular disease due to atherosclerosis, as well as having a positive effect in the prevention of impairment of vascular endothelial cells.

Targeted radionuclide therapy is become increasingly prominent as a nuclear medicine subspe-cialty. For many decades, treatment with radionuclides has been mainly restricted to the use of iodine-131 in thyroid disorders. Currently, radiopharmaceuticals, consisting of a radionuclide coupled to a vector that binds to a desired biological target with high specificity, are being de-veloped. The objective is to be as selective as possible at the tumor level, while limiting the dose received at the healthy tissue level. In recent years, a better understanding of molecular mecha-nisms of cancer, as well as the appearance of innovative targeting agents (antibodies, peptides, small molecules) and the availability of new radioisotopes, have enabled considerable advances in the field of vectorized internal radiotherapy with a better therapeutic efficacy, radiation safety and personalized treatments. For instance, targeting the tumor microenvironment, instead of the cancer cells, now appears as particularly attractive. Several radiopharmaceuticals for therapeutic targeting have shown clinical value in severals types of tumors and have been or will soon be approved and authorized for clinical use.

Background DaVinci Single-Port (SP) robotic surgery offers several benefits compared to traditional multiport laparoscopic or robotic surgeries. One of the main advantages is that it allows for a minimally invasive approach, resulting in a single, smaller incision and reduced trauma to the patient’s body leading to less postoperative pain, faster recovery, and reduced risk of complications. The cosmesis of a single port with minimal visible scarring is also an attractive aspect to the patients; however, many surgeons use an additional port for energy device, stapler use, and drain insertion. Pure single port surgery with one incision is still rare. Here we share our experience of first 10 cases using SP robotic platform in colorectal surgery. Methods From May 2023 to December 2023, colorectal patients who underwent SP-robotic surgery were analyzed. Placement of the incision was umbilicus for 8 patients, and right lower quadrant for 2 patients through which ileostomy maturation was performed. Data including perioperative parameters and postoperative outcomes were analyzed with a median follow-up of 4.6months (range 0.6-7.4months). Results A total number of 10 colorectal patients underwent DaVinci Single-Port robotic colorectal surgery at our institution during this period. Demographics of the patients showed 4 males (40%) and 6 females (60%) with a median age of 63.5years (range 50-75years). Median body mass index (BMI) was 22.89kg/m2 (range 19.92-26.84kg/m2), and 9 patients were diagnosed with colorectal cancer and 1 patient was diagnosed with rectal gastrointestinal tumor. One patient underwent anterior resection and cholecystectomy simultaneously. Mean operation time was 222min (range 142-316min), and mean wound size was 3.25cm (range 2.5-4.5cm). Nine patients underwent surgery with single incision through which single port trocar was inserted, and one patient had one additional port for drain insertion. Mean hospital stay was 6 days (range 4-8 days) with 1 postoperative complication of bleeding requiring transfusion, but there was no re-admission within 30 days. Conclusion Overall, our experience with single-port robotic colorectal surgery has been promising. With only one patient with additional port for drain insertion, all nine patients underwent SP-robotic surgery with single incision for colon as well as rectal surgeries. Compared to an average postoperative length of stay of 6.5-8 days in laparoscopic colorectal surgeries reported in literature, SP-robotic surgery showed faster recovery of 6 days highlighting its benefits in patient recovery and satisfaction.

This study investigated the influence of nutrient inputs and their timing on saffron yield and quality. The study was conducted from 2016 to 2020 and involved the application of eight different fertilization treatments at various stages of saffron growth. These treatments included single doses in Autumn (A), Winter (W), and Spring (S); double doses in Winter-Spring (AW), Autumn-Spring (AS), and Winter-Spring (WS); and a triple dose in Autumn-Winter-Spring (AWS). A control group (C) received no fertilizer. A compound fertilizer with a 15-15-15 composition was applied across all treatments, with nitrogen (N) rates of 67.5 kg/ha for single doses (A, W, S), 135 kg/ha for double doses (AWF, ASF, WSF), and 202.5 kg/ha for the triple dose (AWSF). Similar rates were applied for phosphorus (P) and potassium (K). The findings demonstrated that fertilization generally enhanced saffron attributes. The triple dose treatment yielded the most effective results. The timing of fertilization also played a crucial role, as split applications during different growth stages led to higher production especially winter fertilization. However, spring fertilization had limited impact due to decreased plant activity and reduced nutrient absorption during that period. Although the yield increased, the qualitative aspects of saffron, including color (crocin), taste (picrocrocin), and aroma (safranal), were not significantly influenced by the fertilization treatments. Nevertheless, these attributes remained within the natural limits defined by ISO-3632, indicating that fertilization practices did not compromise saffron quality. Our study highlights the significance of nutrient inputs and their timing in optimizing saffron yield. It provides valuable insights for developing efficient fertilization programs to enhance saffron production while preserving its quality characteristics.

Background. In the central-eastern region of the Mediterranean island of Sardinia more than two decades ago, a mountain area was identified where the population displays exceptional longevity, especially among men (the longevity Blue Zone, LBZ). This community was thoroughly investigated seeking to understand the underlying factors of this phenomenon. In the present study, 11 genetic markers previously associated with longevity in several long-lived populations were analyzed. Methods. APOE (rs429358 and rs7412), APOE promoter (rs449647, rs769446, and rs405509), ACE1 (rs1799752), IL6 ‒174G/C (rs1800795), TNFα ‒308G/A (rs1800629), FOXO3A (rs2802292), KLOTHO (rs9536314) and G6PD (c.563C→T) were investigated. PCR-based genotyping was performed following genomic DNA extraction from 150 nonagenarians living in the LBZ and 150 controls from a nearby area. Results. No significant deviation of the frequency of the analyzed markers was detected between the two groups except a weak association with the –174G&gt;C gene variant of the IL-6 gene (p=0.040), a major modulator of the inflammatory response. Conclusions. The findings of this study do not support a significant association of known genetic variants on survival in the population of the Sardinian LBZ. Other genetic or epigenetic traits might play a role not yet identified.

Sperm gain fertilization ability and forward movement characteristics during epididymal transport. Sperm maturation is inseparable from the processing of the epididymis. Compared with other reproductive organs, relatively little is known about the epididymis. However, with the development of molecular biology and the improvement of single-cell sequence technology, we gradually realized that we should re-examine the importance of the epididymis for sperm mat-uration and for the entire male reproductive system. Recently, epididymis related reports have tended to be more regionalized and more refined. We can understand cell distribution and gene expression from the perspective of a single cell. It has been reported that different regions of the epididymis have different functions and different cell compositions, which may be determined by gene expression. Here, we comprehensively reviewed the epididymal studies. From the ana-tomical structure of the epididymis to the division of its regions, we focused on the cell compo-sition and region-specific genes differentially expressed in the epididymis. The gene expression of the epididymis extends to a series of biological processes of sperm in the epididymal cavity, and the serious effects of epididymal diseases on reproduction are discussed. Therefore, the importance of the epididymis in male reproduction is emphasized. With the maturity of single-cell spatial transcriptomics, it is hoped that the technology can be applied to epididymal research and bring about the spatiotemporal landscape of the epididymis at the single-cell level.

The strong coupling between individual quantum emitters and resonant optical micro/nanocavities is beneficial to understand light and matter interactions. Here we propose a plasmonic nanoantenna placed on a metal film to achieve an ultra-high electric field enhancement in the nanogap and ultra-small optical mode volume. The strong coupling between a single quantum dot and the designed structure is investigated in detail by both numerical simulations and theoretical calculations. When a single QD is inserted into the nanogap of the silver nanoantenna, scattering spectra show remarkably large spectral splitting and typical anti-crossing behavior of the vacuum Rabi splitting, which can be realized in the scattering spectra by varying the nanoantenna thickness. Our work shows a possible way to enhance light-matter interaction at a single quantum emitter limit, which can be useful for future quantum and nanophotonic applications.

An experiment was conducted to investigate the role of single nucleotide polymorphisms of the gene RNF34 3′UTR-588 G>A and RNF128 I1-2380C>T with carcass and meat quality traits of Chinese Simmental-cross steers. METHOD: We performed sequencing and restriction enzyme digestion to detect genotypes of RNF34 3′UTR-588 G>A and RNF128 I1-2380C>T. Then, we analyzed the association of novel single nucleotide polymorphisms in intron regions of the RNF128 gene and in the 3′UTR region of RNF34 and meat quality traits of Chinese Simmental-cross steers. RESULTS: Statistical analyses revealed that SNP of RNF128 (I1-2380C>T) was significantly associated with dressed weight, forepaw weight, carcass depth, carcass brisket depth, hind legs length (P<0.05), etc. And RNF34 (3′UTR-588 G>A) were significantly associated with testis weight, kidney weight, tare weight (P<0.05), etc. CONCLUSION: Our findings suggest that polymorphisms in RNF34 and RNF128 might be important genetic factors that influence carcass and meat quality in beef cattle. Thus, they might be useful markers for meat quality traits in future marker-assisted selection programs in beef cattle breeding and production.

In the last decade, we have witnessed an upsurge in nuclei-based studies, particularly coupled with next-generation sequencing. Such studies aim at understanding the molecular states that exist in heterogeneous cell populations by applying increasingly more affordable sequencing approaches, in addition to optimized methodologies developed to isolate and select nuclei. Although these powerful new methods promise unprecedented insights, it is important to understand and critically consider the associated challenges. Here, we provide a comprehensive overview of the rise of nuclei-based studies and elaborate on their advantages and disadvantages. Improved designs and appropriate use of the various experimental strategies will result in acquiring biologically accurate and meaningful information.

A simulation is performed to analyze the forces that arise in a conducting DNA-like double helix in the field of a microwave electromagnetic wave under half-wave resonance conditions. The helix is comprised of twenty-and-a-half turns and has geometric parameters proportional to the size of an actual DNA molecule. The forces acting on the strands of a double helix, both in the central region and at the edges of the helix, are investigated. It has been demonstrated that the afore-mentioned forces induce a change in the shape of the helix, specifically mutual repulsion of the strands, as well as their stretching and twisting in the field of electromagnetic waves. As opposed to a pair of parallel straight conductors, there is a radial repulsion of strands in all regions of a double DNA-like helix, including the center and the edges. This unique interaction of currents in a double DNA-like helix can be attributed to its pitch angle, a characteristic that has been estab-lished through empirical evidence. Consequently, exposure to an electromagnetic wave under half-wave resonance can damage the double helix. Conversely, the impact of electromagnetic waves has the potential to introduce novel avenues for controlling the shape of the double helix. These nonlinear effects must be considered for both actual DNA molecules and double DNA-like helices that serve as components of metamaterials and metasurfaces.

(1) Background: This study aimed to identify the recurrence and survival rates according to the mismatch repair (MMR), p53, and L1 cell adhesion molecule (L1CAM) states in patients with advanced and recurrent endometrial cancer receiving systemic chemotherapy.; (2) Methods: This single-center retrospective cohort study included chemotherapy-naïve patients (n=156) with advanced-stage (III/IV) or recurrent endometrial cancer who were administered chemotherapy as adjuvant therapy (n=112) or first-line palliative treatment (n=44) between January 2015 and June 2022. MMR and p53 states were assessed using PCR, and L1CAM was tested using immunohistochemistry in the no specific molecular profile (NSMP) group. The primary outcomes were progression-free survival (PFS) and overall survival (OS).; (3) Results: Of the 156 patients, 62 (39.7%), 53 (34.0%), and 41 (26.3%) had NSMP, abnormal p53 (p53abn), and an MMR deficiency (MMR-D), respectively. PFS and OS were longest in MMR-D, followed by NSMP, and were the least in p53abn tumors (PFS: p=0.0006, OS: p=0.0013). After NSMP was classified according to positive or negative L1CAM status, the L1CAM-negative group exhibited significantly lower survival rates than the L1CAM-positive group (PFS: p=0.0001, OS: p=0.0027); p53abn tumors were independent prognostic factors for poor PFS (p=0.039 on the multivariable analysis).; (4) Conclusions: In chemotherapy-naïve patients with advanced and recurrent endometrial cancer, the best prognosis after chemotherapy was obtained using MMR-D, followed by NSMP and p53abn tumors. The L1CAM status is a useful new marker for stratifying NSMP in advanced and recurrent patients.

Besides external high-energy photon or proton beam therapy, targeted radionuclide therapy (TRNT) is an alternative approach to deliver radiation to cancer cells. TRNT is distributed within the body by the vascular system and allows targeted irradiation of a primary tumor and all its metastases, resulting in substantially less collateral damage to normal tissues as compared to ex-ternal beam radiotherapy (EBRT). It is a systemic cancer therapy, tackling systemic spread of the disease, which is the cause of death in most cancer patients. The α-emitting radionuclide bis-muth-213 (213Bi) has interesting properties and can be considered as a magic bullet for TRNT. The benefits and drawbacks of targeted alpha therapy with 213Bi are discussed in this review, covering the entire chain from radionuclide production to bedside. First, the radionuclide properties and production of 225Ac and its daughter 213Bi are discussed, followed by the fundamental chemical properties of bismuth. Next, an overview of available acyclic and macrocyclic bifunctional chelators for bismuth, and general considerations for designing a 213Bi-radiopharmaceutical are provided. Finally, we will provide an overview of preclinical and clinical studies involving 213Bi-radiopharmaceuticals, as well as the future perspectives of this promising cancer treatment option.

Water deficit caused by drought is a significant threat to crop growth and production. Nitric oxide (NO), a water- and lipid-soluble free radical, plays an important role in cytoprotection. Apart from a few studies supporting the role of NO in drought responses, little is known about this pivotal molecular amendment in the regulation of abiotic stress signaling. In this review, we highlight the knowledge gaps in NO roles under drought stress and the technical challenges underlying NO detection and measurements, and we provide recommendations regarding potential avenues for future investigation. The modulation of NO production to alleviate abiotic stress disturbances in higher plants highlights the potential of genetic manipulation to influence NO metabolism as a tool with which plant fitness can be improved under adverse growth conditions.

Primary hyperoxalurias (PHs) are a group of inherited alterations of the hepatic glyoxylate metabolism. PHs classification based on gene mutations parallel a variety of enzymatic defects, and all involve the harmful accumulation of calcium oxalate crystals that produce systemic damage. These geographically widespread rare diseases have a deep impact in the life quality of the patients. Until recently, treatments were limited to palliative measures and kidney/liver transplants in the most severe forms. Efforts made to develop pharmacological treatments succeeded with the biotechnological agent lumasiran, a siRNA product against glycolate oxidase, which has become the first effective therapy to treat PH1. However, small molecule drugs have classically been preferred since they benefit from experience and have better pharmacological properties. The development of small molecule inhibitors designed against key enzymes of glyoxylate metabolism is on the focus of research. Enzyme inhibitors are successful and widely used in several diseases and their pharmacokinetic advantages are well known. In PHs, effective enzymatic targets have been determined and characterized for drug design and interesting inhibitory activities have been achieved both in vitro and in vivo. This review describes the most recent advances towards the development of small molecule enzyme inhibitors in the treatment of PHs, introducing the multi-target approach as a more effective and safe therapeutic option.

In this paper we propose the generation of synthetic small and more sophisticated molecule structures that optimize the binding affinity to a target (ASYNT-GAN). To achieve this we leverage on three important achievements in A.I.: Attention, Deep Learning on Graphs and Generative Adversarial Networks. Similar to text generation based on parts of text we are able to generate a molecule architecture based on an existing target. By adopting this approach, we propose a novel way of searching for existing compounds that are suitable candidates. Similar to question and answer Natural Language solutions we are able to find drugs with highest relevance to a target. We are able to identify substructures of the molecular structure that are the most suitable for binding. In addition, we are proposing a novel way of generating the molecule in 3D space in such a way that the binding is optimized. We show that we are able to generate compound structures and protein structures that are optimised for binding to a target.

Room-temperature phosphorescent (RTP) materials have been attracted tremendous interest owing to their unique material characteristics and potential applications for state-of-the-art optoelectronic devices. Recently, we have reported a synthesis and fundamental photophysical properties of new RTP materials based on benzil, i.e., fluorinated monobenzil derivative and fluorinated and non-fluorinated bisbenzil derivative analogues [Yamada, S. et al, Beilstein J. Org. Chem. 2020, 16, 1154–1162.]. To further understand their RTP properties, here we investigated the excited-state dynamics and photostability of the derivatives by means of time-resolved and steady-state photoluminescence spectroscopies. For these derivatives, clear RTP emissions with lifetimes on the microsecond timescale were identified. Among them, the monobenzil derivative was found to be the most efficient RTP material, showing both the longest lifetime and highest amplitude RTP emission. Time-resolved photoluminescence spectra measured at 77 K and density functional theory calculations revealed the existence of a second excited triplet state in the vicinity of the first excited singlet state for the monobenzil derivative, indicative of the presence of a fast intersystem crossing pathway. A discussion of the correlation between the excited state dynamics, emission properties, and conformational flexibility of the three derivatives is presented.

It is proposed that the primary living cells (“probionts”) cannot emerge of organic substance simply by continuous chemical complication of prebiotic macromolecules and microsystems. The complication must be accompanied by the radical thermodynamic transformation (“jump”) of prebiotic microsystems that resulted in the acquired ability to extract free energy from the environment and export entropy. This transformation is called “the thermodynamic inversion” The inversion may occur by means of the efficient (intensified) response of the microsystems on the oscillations of physic-chemical parameters in hydrothermal environment. In this case the surplus available free energy within a microsystem, when combined with the informational modality, facilitates its conversion into a new microsystem—a living probiont. It is shown the schematic representation of an oscillating prebiotic microsystem that is transforming into a living probiont. A new kind of laboratory and computational experiments on prebiotic chemistry under oscillating conditions is offered to verify the inversion concept.

Polychlorinated phenoxathiins (PCPTs), polychlorinated dibenzothiophenes (PCDTs), and polychlorinated thianthrenes (PCTAs) are sulfur analogues of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/DFs). Chlorothiophenols(CTPs) and chlorophenols (CPs) are key precursors to form PCTA/PT/DTs, which can form chloro(thio)phenoxy radical, sulfydryl/hydryl-substituted phenyl radical and (thio)phenoxyl diradicals. The available radical/radical PCTA/DT formation mechanism failed to explain the higher concentration of PCDTs than that of PCTAs under the pyrolysis or combustion conditions. Thus in this work, a detailed thermodynamics and kinetic calculations were carried out to investigate the pre-intermediates formation for PCTA/PT/DTs from radial/molecule coupling of 2-C(T)P with their key radical species. Our study found that the radial/molecule mechanism can thermodynamically and kinetically contribute to the gas-phase formation of PCTA/PT/DT/s. The S/C coupling modes to form thioether-(thio)enol intermediats are preferable over the O/C coupling modes to form ether-(thio)enol intermediats. Thus, although the radial/molecule coupling of chlorophenoxy radical with 2-C(T)P have no effect on the PCDD/PTs formation, the radial/molecule coupling of chlorothiophenoxy radical with 2-C(T)P play an important role in the PCDT/PT formation. Most importantly, the pre-PCDT intermediates formation pathways from the coupling of sulfydryl/hydryl-substituted phenyl radical with 2-C(T)P and the coupling of (thio)phenoxyl diradicals with 2-C(T)P are more favorable to pre-PCTA/PT intermediates formation pathways from the coupling of chlorothiophenoxy radical with 2-C(T)P, which can give reasonable explanation for the high PCDT-to-PCTA ratio in the environment.

Natural and synthetic small molecules from the NCI Developmental Therapeutics Program (DTP) were employed in molecular dynamics-based docking with DNA repair proteins whose RNA-Seq based expression was associated with overall cancer survival (OS) after adjustment for the PCNA metagene. The compounds employed were required to elicit a sensitive response (vs. resistance) in more than half of the cell lines tested for each cancer. Methodological approaches included peptide sequence alignments and homology modeling for 3D protein structure determination, ligand preparation, docking, toxicity and ADME prediction. Docking was performed for unique lists of DNA repair proteins which predict OS for AML, cancers of the breast, lung, colon, and ovaries, GBM, melanoma, and renal papillary cancer. Results indicate hundreds of drug-like and lead-like ligands with best-pose binding energies less than -6 kcal/mol. Ligand solubility for the top 20 drug-like hits approached lower bounds, while lipophilicity was acceptable. Most ligands were also blood-brain barrier permeable with high intestinal absorption rates. While the majority of ligands lacked positive prediction for Herg channel blockage and Ames carcinogenicity, there was considerable variation for predicted fathead minnow, honey bee, and Tetrahymena pyriformis toxicity. The computational results suggest the potential for new targets and mechanisms of repair inhibition and can be directly employed for in vitro and in vivo confirmatory laboratory experiments to identify new targets of therapy for cancer survival.

The molten salt reactor (MSR) specific 3D spatial dynamics code leveraging the neutronics and thermal-hydraulics (TH) coupling method, TMSR3D, has been extended for static and transient analysis of large advanced light water reactors (LWRs), particularly focusing on control rod ejection accidents. The code is built upon the neutron diffusion model leveraging the widely used "two-step" strategy in three-dimensional Cartesian coordinates. A polynomial nodal expansion method (NEM) is utilized to handle spatial variables, while the neutron kinetics solver employs the exponential transformation technique. The code also integrates a single-channel TH module and a steam table set at 15.5 Mpa. The accuracy of the code has been validated through three transient benchmarks, including the 3D-LRA benchmark for boiling water reactors (BWRs), the NEACRP 3D benchmark, and the MOX/UO2 core benchmark for pressurized water reactors (PWRs). These benchmarks cover both static and transient behaviors, and the results have been thoroughly analyzed. The close alignment of extended version of TMSR3D outcomes with reference data and other codes supports its reliability, making it a promising tool for future dynamic analyses of large-scale advanced PWRs.

Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and the most common form of head and neck cancer, posing significant challenges for disease management. Single-cell RNA sequencing (sc-RNAseq) has emerged as a valuable tool for addressing these challenges by enabling detailed characterization of the tumor microenvironment (TME) at the cellular level. This review assesses the utility of sc-RNAseq in HNSCC research, compiling current strategies employing single-cell technologies. For HNSCC etiology, sc-RNAseq allows for the construction of cellular atlases, characterization of different cell types, and investigation of key genes and processes involved in cancer initiation, development, and progression within the TME. In terms of HNSCC diagnosis and prognosis, the high resolution offered by sc-RNAseq enables the identification of cell type-specific signatures, enhancing prognostic models and disease stratifiers for more accurate patient outcome assessments. Regarding HNSCC treatment, sc-RNAseq provides insights into cellular responses to various treatments, including radiotherapy, chemotherapy, and immunotherapy, contributing to improved patient stratification and personalized treatment strategies. This review highlights the unique contributions of sc-RNAseq to HNSCC research, addressing its cellular and biological complexity, and emphasizes its potential for advancing research and clinical practice in other cancer types.

We fabricated high-quality MAPbBr3 single crystals (SC) by introducing moderate amount electron-rich poly(propylene glycol bis(2-aminopropyl ether) (PEA) additives with an inverse temperature crystallization (ITC) method. The intramolecular vibrations and defective states of prepared MAPbBr3 single crystals were systemically studied by the in situ variable-temperature Fourier Transform Infrared (FTIR) Spectroscopy, X-ray photoelectron spectroscopy (XPS), and the synchrotron-based X-ray absorption near edge structure (XANES), et al. We infer that the proper amount of PEA additives would prevent the formation of intermediate states and crystal boundaries, passivating the density of defective states. The X-ray detection properties of single-crystal MAPbBr3 crystals were investigated, using both high dose and low dose X-ray photons at 40keV in synchrotron beamlines. The photocurrent of optimized PEA-treated MAPbBr3 single crystals demonstrate better performance compared with the as-prepared single crystals. Meanwhile, the decay time of MAPbBr3 single crystal is decreased from 460 ns to 210 ns by Time-resolved photoluminescence (TRPL) decay measurement, owing to the defect passivation by 0.5wt% PEA additives. The PEA-treated single crystals possess much faster decay time than the commercialized Ce:YAG scintillator (>500ns). These results help elucidate the passivation of defective states and contribute paths to manufacture high-quality single crystal perovskites for next-generation optoelectronic devices.

The first single crystal structure of the homoleptic copper (II) ML2 complex (M=Cu (II), L=curcumin) was obtained and its structure was elucidated by X-ray diffraction showing a square planar geometry. The supramolecular arrangement is supported by C-H···O interactions and the solvent (MeOH) plays an important role in stabilizing the crystal packing. The cytotoxic activity of the complex against six cancer cell lines substantially surpasses that of curcumin itself, and it is particularly selective against leukemia (K562) and human glioblastoma (U251) cell lines with similar antioxidant activity to BHT. This constitutes the first crystal structure of pristine curcumin complexed with a metal ion.

Cancer is a multifactorial disease that continues to increase. Lignans are known to be important anticancer agents. However, due to the structural diversity of lignans, it is difficult to associate anticancer activity with a particular subclass. Therefore, the present study sought to evaluate the association of lignan subclasses with antitumor activity, considering the genetic profile of the variants of the selected targets. For this, predictive models were built against the targets tyrosine-protein kinase ABL (ABL), epider-mal growth factor receptor erbB1 (EGFR), histone deacetylase (HDAC), Serine/threonine-protein kinase mTOR (mTOR) and Poly [ADP-ribose] polymerase-1 (PARP1). Then, mapped single nucleotide polymorphisms and designed target mutations, and performed molecular docking with the lignans with the best predicted biological activity. The results showed more anticancer activity in the dibenzocyclooctadiene, furofuran and aryltetralin subclasses. The lignans with the best predictive values of biological activity showed varying binding energy results in the presence of certain genetic variants.

Atypical hemolytic uremic syndrome (aHUS) is a rare and life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury, necessitating differentiation from other thrombotic microangiopathy disorders. Definitive biomarkers for disease diagnosis and activity are currently lacking, and identifying molecular markers is essential. We conducted single-cell sequencing on peripheral blood mononuclear cells from 13 aHUS patients, 3 aHUS family members, and 4 healthy controls. Analysis included clustering, cell type annotation, pseudotime estimation, and cell-cell communication. Immune cell populations differ among aHUS, aHUS families, and healthy controls. Disease activity and treatment influence T, NK, B, and monocyte subpopulations, with increased intermediate monocyte levels distinguishing aHUS from controls and aHUS groups with varying disease activity. Subclustering revealed differential gene expression in patients compared to controls; higher expression of mitochondria-related genes suggests cell metabolism may influence clinical course. Pseudotime trajectory analysis demonstrated unique immune cell differentiation, and cell-cell interaction analysis identified distinct signaling pathways among patients, family members, and controls. This single-cell sequencing study is the first to confirm immune cell dysregulation in aHUS pathogenesis, offering valuable insights into molecular mechanisms and potential new diagnostic and disease activity markers.

A quantum Otto engine with a single ion harmonic oscillator as its working substance is studied for an adiabatic operation at high and low temperature limits. Using the universal optimization method, the heat engine is effectively optimized and found to yield better working conditions in some ranges of temperature ratios. Accordingly, the figure of merit, ψ, is found to be greater than unity in the range: 0&lt;β2β1≤0.12; showing that the heat engine performs better in the optimized condition than in the maximum power working condition. ψ is determined to be less than one in the range 0.12≤β2β1≤0.35 under the same temperature limit ; depicting that the maximum power working condition is preferred to the optimized working condition. On the other hand, in the low temperature limit, the figure of merit, ψ, is found to be greater than unity in the range 3.7&lt;ω1ω2≤18; revealing that optimized working condition is better than the maximum power working condition for the heat engine. In the same temperature limit, ψ is found to be less than one in the range 0≤ω1ω2≤3.7; showing that maximum power working condition is preferred to the optimized one. For the model of heat engine studied, in some ranges of temperature ratio, it is found to work better in the optimized condition, whereas in the other ranges it performs better under the maximum power working condition. So, it is possible to switch the engine between the two conditions depending on one’s need.

Glioblastoma (GBM) is the most common primary brain tumor in adults, with few available therapies and a 5-year survival rate of 7.2%. Hence, strategies for improving GBM prognosis are urgently needed. The translocator protein 18kDa (TSPO) plays crucial roles in essential mito-chondria-based physiological processes and is a validated biomarker of neuroinflammation, which is implicated in GBM progression. The TSPO gene has a germline single nucleotide pol-ymorphism, rs6971, which is the most common SNP in the Caucasian population. High TSPO gene expression is associated with reduced survival in GBM patients; however, the relation between the most frequent TSPO genetic variant and GBM pathogenesis is not known. The present study ret-rospectively analyzed the correlation of the TSPO polymorphic variant rs6971 with overall and progression-free survival in GBM patients using three independent cohorts. TSPO rs6971 poly-morphism was significantly associated with shorter overall survival and progression-free survival in male GBM patients but not in females in one large cohort of 441 patients. We observed similar trends in two other independent cohorts. These observations suggest that the TSPO rs6971 pol-ymorphism could be a significant predictor of poor prognosis in GBM, with a potential for use as a prognosis biomarker in GBM patients. These results reveal for the first time a biological sex-specific relation between rs6971 TSPO polymorphism and GBM.

“Clickase” single-chain nanoparticles (Ck-SCNPs) are folded, enzyme-mimetic unimolecular polymeric nano-objects containing copper (Cu) ions able to catalyze the azide-alkyne Huisgen cycloaddition reaction in water and/or selected organic solvents, often in the presence of a reductant. Herein, we investigate the effect of morphology on catalytic activity of Ck-SCNPs synthesized by means of two different routes. An amphiphilic random copolymer composed of oligo(ethylene glycol) methyl ether methyl methacrylate (OEGMA) and 2-acetoacetoxy ethyl methacrylate (AEMA) units was used as precursor of these Ck-SCNPs. Folding was promoted through metal complexation between Cu(II) ions and beta-ketoester-containing AEMA moieties. The first route resulted in Ck-SCNPs1 containing Cu ions homogeneously distributed within each nanoparticle, whereas the second one promoted intra-chain clustering of Cu ions inside Ck-SCNPs2. A model fluorogenic “click” reaction between 9-(azidomethyl)anthracene and phenylacetylene, which was catalyzed either by Ck-SCNPs1 or Ck-SCNPs2, was used to unravel the effect of morphology on catalytic activity. This work paves the way to improve the catalytic activity of metallo-folded SCNPs through control of the intra-chain distribution of catalytic sites.

Single cell proteins are the dead dried cells of microorganisms or purified protein isolated from microorganism’s cell culture, used as a food supplement to humans’ food and animals feed. World suffer from malnutrition particularly developing countries, due to rapid increase in population, increased the demand for protein and nutrients requirement. Bacteria is potential microorganism for SCP production due to high protein content, fast generation time, bio-active secondary metabolites production and can grow on various substrates. Actinobacteria species and strain have capability to produce biological active compounds, produced about two-thirds of antibiotics available in the market, actively used as antibiotics, antiprotozoal, antifungal, antiviral, anticancer, anticholesterol, antihelminth and immunosuppressant. Actinomycetes can be used as probiotic as well as single cell protein that will deal with antibiotic as well as protein source.

The present study investigates the failure mechanisms of industrial fiber materials, using a custom designed fiber cutting performance test bench. The fracture morphologies of single PA6 fibers are examined by scanning electron microscopy. The analysis reveals that fiber cutting can be distinguished according to four distinct stages of fiber failure represented by shearing, cutting, brittle fracture, and tensile failure, which are the result of different mechanisms active during the processes of crack initiation, extension and fracture. The results of fractographic analysis are further verified by an analysis of the blade assembly speed with respect to time over the entire fracture failure process based on high-speed camera data. The results of fractographic analysis and blade assembly speed are fully consistent.

Tight junctions (TJ) are cell-cell adhesive structures that define the permeability of barrier-forming epithelia and endothelia. In contrast to this seemingly static function, TJs display a surprisingly high molecular complexity and an unexpected dynamic regulation, which allows the TJs to maintain a barrier in the presence of physiological forces and in response to perturbations. Cell-cell adhesion receptors play key roles during the dynamic regulation of TJs. They connect individual cells within cellular sheets and link sites of cell-cell contacts to the underlying actin cytoskeleton. Recent findings support roles of adhesion receptors in transmitting mechanical forces and promoting phase separation. In this review, we discuss newly discovered functions of cell adhesion receptors localized at the TJs and their role in the regulation of the barrier function.

Infection of hosts by morbilliviruses is facilitated by the interaction between viral hemagglutinin (H-protein) and the signaling lymphocytic activation molecule (SLAM). Recently, the functional importance of the N-terminal region of human SLAM as a measles virus receptor was demonstrated. However, the functional roles of this region in the infection process by other morbilliviruses and host range determination remain unknown partly because this region is highly flexible, which has hampered accurate structure determination of this region by X-ray crystallography. In this study, we analyzed the interaction between the H-protein from canine distemper virus (CDV-H) and SLAMs by a computational chemistry approach. Molecular dynamics simulations and fragment molecular orbital analysis demonstrated that the unique His28 in the N-terminal region of SLAM from Macaca is a key determinant that enables formation of a stable interaction with CDV-H, providing a basis for CDV infection in Macaca. The computational chemistry approach presented should enable determination of molecular interactions involving regions of proteins that are difficult to predict from crystal structures because of their high flexibility.

Discovery of inhibitors for endothelial-related transcription factors can contribute to the development of angiogenic therapies that treat diseases ranging from cardiovascular to cancer. The role of transcription factor Vezf1 in vascular development and regulation of angiogenesis has been defined by several earlier studies. Through construction of a computational model for Vezf1, work here has identified a novel small molecule drug capable of inhibiting Vezf1 from binding to its cognate DNA binding site. Using structure-based design and virtual screening of the NCI Diversity Compound Library, 12 shortlisted compounds were tested for their ability to interfere with the binding of Vezf1 to DNA using electrophoretic gel mobility shift assays. We identified one compound, T4, which has an IC50 of 20uM. Using murine endothelial cells, MSS31, we tested the effect of T4 on endothelial cell viability and angiogenesis by using tube formation assay. Our data show that addition of T4 in cell culture medium does not affect cell viability at concentrations lower or equal to its IC 50 but strongly inhibits the network formation by MSS31 in the tube formation assays. Given its potential efficacy, this inhibitor has significant therapeutic potential in several human diseases raging from wound healing to cancer.

The World Health Organization (WHO) recently added snakebite envenoming to the priority list of Neglected Tropical Diseases (NTD). It is thought that ~75% of mortality following snakebite occurs outside the hospital setting, making the temporal gap between a bite and antivenom administration a major therapeutic challenge. Small molecule therapeutics (SMTs) have been proposed as potential pre-referral treatments for snakebite to help address this gap. Herein, we discuss the characteristics, potential uses and development of SMTs as potential treatments for snakebite envenomation. We focus on SMTs that are secretory phospholipase A2 (sPLA2) inhibitors and metalloprotease (MP) inhibitors.

It is well known that fiber sizing is one of the most important component in the manufacturing of composites, and it does affect the mechanical properties including strength and stiffness. In this work, the influence of fiber sizing levels on the mechanical properties of carbon fibers (CF) is reported at room temperature by using single fiber tensile testing (Favimat+), single fiber pullout testing (SFPO), and interfacial elemental analysis using X-ray photoelectron spectroscopy (XPS). Standard modulus of CF (7±0.2 μm in diameter) were sized using two Michelman commercially available sizing formulations. The average solid content for each sizing formulation is 26.3 ± 0.2% and 34.1 ± 0.2%, respectively. HEXION RIMR 135 with curing agent RIMH 137 was used as a model thermoset epoxy matrix during the SFPO measurements. A predictive engineering fiber sizing methodology is also developed. Sizing amounts of 0.5, 1, and 2 wt. % on the surface of the fiber is achieved for both sizing formulations. For each fiber sizing level, 50 single fiber tensile testing experiments and 20 single fiber pull-out tests were conducted. The ultimate tensile strength (σult) of the carbon fibers and the interfacial shear strength (τ_app) of the single fiber composite were analyzed. it is also investigated the effect of the sizing levels on the interfacial shear stress and the O/C (Oxygen/Carbon) surface composition ratio. As a result, generalized fiber sizing and characterization methods were established. The developed methods can be used to characterize the strength and interfacial shear strength of any man-made fibers with different sizing formulations and solid contents, irrespective of the matrix i.e. thermoset or thermoplastic.

Numerous dynamic and complicated processes characterize development from the oocyte to the embryo. However, given the importance of functional transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms, and alternative splicing during embryonic development, the effect that these features have on the blastomeres of 2-, 4-, 8-, 16-cell, and morula stages of development have not been studied. Here, we conducted a scRNA-seq survey of cells from sheep from the oocyte to the blastocyst developmental stages. We then carried out experiments to identify and functionally analyze the transcriptome profiles, long non-coding RNAs, single-nucleotide polymorphisms (SNPs), and alternative splicing (AS). We founded that between the oocyte and zygote groups significantly down-regulated genes and the second-largest change in gene expression occurred between the 8- and 16-cell stages. We used various methods to construct a profile to characterize cellular and molecular features and systematically analyze the related GO and KEGG profile of cells of all stages from the oocyte to the blastocyst. This large-scale, single-cell atlas provides key cellular information and will likely assist clinical studies in improving preimplantation genetic diagnosis.

Localization accuracy in non-line-of-sight (NLOS) scenarios is often hindered by the complex nature of multipath propagation. Traditional approaches typically focus on NLOS node identification and error mitigation techniques. However, the intricacies of NLOS localization are intrinsically tied to propagation challenges. In this paper, we propose a novel single-site localization method tailored for complex multipath NLOS environments, leveraging only angle of arrival (AOA) estimates in conjunction with a ray-tracing (RT) algorithm. The method transforms NLOS paths into equivalent line-of-sight (LOS) paths through the generation of generalized sources (GSs) via ray tracing. A novel weighting mechanism for GSs is introduced, which, when combined with an iteratively reweighted least squares (IRLS) estimator, significantly improves the localization accuracy of non-cooperative target sources. Furthermore, a multipath similarity displacement matrix (MSDM) is incorporated to enhance accuracy in regions with pronounced multipath fluctuations. Simulation results validate the efficacy of the proposed algorithm, achieving localization performance that approaches the Cramér-Rao lower bound (CRLB), even in challenging NLOS scenarios.

p97(also known as Cdc48 or VCP) is a conserved AAA+ ATPase that plays a key role in diverse cellular pathways and processes. p97 segregates damaged or misfolded substrates from cellular organelles or membranes in corporation with its cofactors. These cofactors regulate p97’s function by its directing to different cellular pathways and have diverse effect on p97´s conformation. Recently, several high-resolution structures of substrate-engaged p97 in complex with cofactors have been resolved, providing structural insights into the molecular mechanism of substrate processing. In this review, we present a comprehensive overview of how p97 in complex with substrate recruiting and substrate processing cofactors recognize, extract, translocate, unfold and release ubiquitinated substrates.

For very first time, we report the synthesis of 8-(2-methoxyphenyl)-6-methyl-2-(1-methyl-1H-benzo[d]imidazol-2-yl)quinoline 1. This was achieved in several steps, including usage of Suzuki reaction for functionalization of 2-(1H-benzo[d]imidazol-2-yl)quinoline moiety. The new compound exhibits blue fluorescence. Its structure was confirmed with 1D- and 2D-NMR spectroscopy, IR-spectroscopy, high-resolution mass spectrometry and X-ray analysis.

Solving the problem of searching for new scintillators based on available materials, we were the first to obtain and study a single crystal of CsI doped with divalent ytterbium ions. This work was directed to study of luminescence mechanism of Yb2+ ions and excitation transfer from crystalline matrix of CsI to dopant ions under VUV excitation. Using time-resolved spectroscopy, spin-allowed and spin-forbidden radiative transitions of ytterbium ions at room temperature were discovered. At 10 degrees, the emission of self-trapped excitons was detected. UV and VUV excitation spectra were obtained in the emission bands of ytterbium and self-trapped excitons. It was found that Yb2+ luminescence is excited in the excitonic region in the range of 10-45 eV. The mechanism of charge compensation of Yb2+ ions in a CsI crystal was also studied, the spectrum of the thermally stimulated depolarization current was measured, and the activation energies of the two observed peaks were calculated. These peaks belong to impurity-vacancy complexes in two different positions.It is concluded that Yb2+ ions are promising dopants for CsI scintillators and X-ray phosphors in combination with SiPM photodetectors.

Introduction: The association of gene variants for interleukin 6(IL-6) (rs1800796), interleukin 10 (IL-10) (rs1800896) and tumor necrosis factorα (TNFα (rs1800629) with the occurrence of spontaneous preterm birth (PTB) was investigated to determine whether these genetic variants are a risk factor. Materials and methods: 199 blood samples from pregnant women who had given birth prematurely and 200 control blood samples were analyzed to determine single nucleotide polymor-phisms (SNPs) of genes for IL-6 (rs1800796), IL-10 (rs1800896) and TNFα (rs1800629). The control samples were samples from pregnant women with term delivery. Isolation of DNA was per-formed on mini-spin columns according to the manufacturer's protocol. The quality and purity of the isolated DNA were tested using a Qubit 3 fluorometer. Genotyping was performed with an ABI PRISM 7500 SDS using TaqMan SNP genotyping assays. The genotypes obtained were an-alyzed using the 7500 Software v2.3 package. Results: Carriers of the A/A genotype for the rs1800629 of the TNFα gene have 4.81 times greater chance of late-onset PTB compared to carriers of the G/G and A/G genotypes in the recessive inheritance model. The presence of the G/G genotype in the recessive inheritance model compared with the G/A and A/A genotypes for the rs1800896 of the IL-10 gene represents a potentially protective factor, with mothers in the term-birth group having an almost 2-fold lower odds of PTB in general and an almost 10-fold lower odds of early PTB. On the other hand, carriers of the A/G genotype of rs1800896 have a 1.54-fold higher chance of preterm birth in general and a 1.6-fold higher chance of late preterm birth in the super dominant inheritance model compared to the A/A and G/G genotypes in the group of mothers with PTB. In this study, no association was found between PTB and rs1800796 of the IL-6 gene. Conclusion: rs1800629 in mothers was associated with PTB. rs1800896 shows a potentially protective effect for the occurrence of PTB in this study. No association was found between PTB and rs1800796.

Effectively addressing juvenile delinquency among adolescents in Nigeria necessitates a keen focus on parenting styles and family structures. Given that parents serve as primary custodians and paramount influencers in socializing their children, their pivotal roles cannot be understated. When parents conscientiously strive to exemplify positive role models for their children, the likelihood of yielding optimal and desired outcomes is significantly enhanced. Regrettably, a considerable number of parents have embraced parenting styles that inadvertently expose their children to various forms of juvenile delinquency. The article explores the complex relationship between parenting styles and juvenile delinquency, shedding light on the connections between family structure and delinquent behavior. Also, the connection between marital discord and juvenile delinquency as well as the impacts of single parenting, were explored. The theoretical framework employed in this article is the Social Learning Theory, formulated by Albert Bandura in 1977. The article underlines that a substantial portion of delinquent acts among adolescents can be attributed to familial discord and the specific parenting styles employed. Consequently, this study advocates for a paradigm shift towards more effective and constructive parenting styles. Additionally, it emphasizes the imperative for the government and relevant institutions to accord due importance to the institution of the family in their policies and interventions.

We are currently investigating the ultrasound imaging of a sensor consisting of a randomized encoding mask attached to a single lead zirconate titanate (PZT) oscillator for use in a puncture microscope. The proposed model was performed using a finite element method (FEM) simulator. To increase the number of measurements required by a single element system, the transducer was rotated at different angles. The image was constructed by solving a linear equation of the image model. In a previous study, the image resolution was improved by extracting phase information. In this study, we propose a strategy by integrating the weighted frequency subbands compound and a super resolution method (SCM) to improve the resolution in range and lateral resolution. We also evaluated the image performance by applying different methods to improve the image quality. The results show that better image resolution and speckle suppression were obtained by applying the proposed method.