Search Results (304,086)

Background: Studies on night sleep and parental bedtime practices and their associations with language development in populations at risk of language delay and neonatal conditions, such as late talkers and preterm children, are scarce. Objectives: Our objective was to longitudinally examine the development of night sleep (total night sleep difficulties, settling, night waking, and co-sleeping), parental bedtime practices (total parental bedtime practices, active physical comforting, encouraging autonomy, and leaving to cry), and expressive language (word and sentence production), and their associations in low-risk preterm and full-term late talkers from 31 to 37 months of age. Methods: Parents of 38 late talkers, 19 low-risk preterm and 19 full-term children, completed the Italian versions of the Infant Sleep Questionnaire, the Parental Interactive Bedtime Behavior Scale, and the MacArthur-Bates Communicative Development Inventory Words and Sentences Long Form. Results: Late talkers’ night sleep difficulties, such as settling to sleep and night waking, decreased over time, with low-risk preterm late talkers experiencing more night waking and co-sleeping than full-term peers. Parents reported that instances of active physical comforting and leaving to cry also decreased, with parents of low-risk preterm late talkers reporting higher active physical comforting scores than parents of full-term peers. Improvements in parental practices of encouraging autonomy were significantly associated with increased sentence production from 31 to 37 months. Conclusions: Findings highlight the importance of monitoring night sleep in preterm and full-term late talkers. They also suggest that populations vulnerable to sleep and language delays may particularly benefit from targeted interventions promoting autonomy in their bedtime routines, which, in turn, could support their language development trajectories. Full article

Auditory hair cell damage induced by aminoglycoside antibiotics (AmAn) leads to hearing loss, which has a serious effect on people’s mental and physical health. This ototoxicity is thought to be related with the excessive accumulation of reactive oxygen species (ROS) in hair cells. However, therapeutic agents that protect hair cells are limited. Marine peptides have been shown to have excellent potential applications in disease prevention and treatment. Therefore, this study investigated the protective effects of an active peptide from Neptunea arthritica cumingii against AmAn-induced hair cell damage using the model of hair cell damage zebrafish. We identified the number, ultrastructure, and function of hair cells using fluorescence probes and scanning electron microscopy. The uptake of AmAn, ROS level, mitochondrial permeability transition pore, and apoptosis in hair cells were also tested by fluorescence labeling and TUNEL assay. The molecular mechanism for hair cell protection exerted by the peptide was detected by a real-time quantitative PCR assay. The results indicated that the peptide suppressed the uptake of AmAn but did not damage the function of hair cells mediating hearing. It also prevented ROS accumulation, decreased the occurrence of apoptosis, and rescued the abnormal opening and expressions of mitochondrial permeability transition pore and genes related to antioxidants. The peptide may be an effective therapeutic agent for AmAn-induced ototoxicity. In the future, we plan to use mammalian models to further investigate the otoprotective effect of the peptide. Full article

Ammonia (NH₃) gas is prevalent in industrial production as a health hazardous gas. Consequently, it is essential to develop a straightforward, reliable, and stable NH₃ sensor capable of operating at room temperature. This paper presents an innovative approach to modifying SnO₂ colloidal quantum dots (CQDs) on the surface of Ti₃C₂T_x MXene to form a heterojunction, which introduces a significant number of adsorption sites and enhances the response of the sensor. Zero-dimensional (0D) SnO₂ quantum dots and two-dimensional (2D) Ti₃C₂T_x MXene were prepared by solvothermal and in situ etching methods, respectively. The impact of the mass ratio between two materials on the performance was assessed. The sensor based on 12 wt% Ti₃C₂T_x MXene/SnO₂ composites demonstrates excellent performance in terms of sensitivity and response/recovery speed. Upon exposure to 50 ppm NH₃, the frequency shift in the sensor is −1140 Hz, which is 5.6 times larger than that of pure Ti₃C₂T_x MXene and 2.8 times higher than that of SnO₂ CQDs. The response/recovery time of the sensor for 10 ppm NH₃ was 36/54 s, respectively. The sensor exhibited a theoretical detection limit of 73 ppb and good repeatability. Furthermore, a stable sensing performance can be maintained after 30 days. The enhanced sensor performance can be attributed to the abundant active sites provided by the accumulation/depletion layer in the Ti₃C₂T_x/SnO₂ heterojunction, which facilitates the adsorption of oxygen molecules. This work promotes the gas sensing application of MXenes and provides a way to improve gas sensing performance. Full article

Postmenopausal osteoporosis is a major global health concern, particularly affecting aging women, and necessitates innovative treatment options. Herbal medicine, with its multi-compound, multi-target characteristics, offers a promising approach for complex diseases. In this study, we applied multiscale network and random walk-based analyses to identify candidate herbs and their active ingredients for postmenopausal osteoporosis, focusing on their underlying mechanisms. A dataset of medicinal herbs, their active ingredients, and protein targets was compiled, and diffusion profiles were calculated to assess the propagation effects. Through correlation analysis, we prioritized herbs based on their relevance to osteoporosis, identifying the top candidates like Benincasae Semen, Glehniae Radix, Corydalis Tuber, and Houttuyniae Herba. Gene Set Enrichment Analysis (GSEA) revealed that the 49 core protein targets of these herbs were significantly associated with pathways related to inflammation, osteoclast differentiation, and estrogen metabolism. Notably, compounds such as falcarindiol from Glehniae Radix and tetrahydrocoptisine from Corydalis Tuber—previously unstudied for osteoporosis—were predicted to interact with inflammation-related proteins, including IL6, IL1B, and TNF, affecting key biological processes like apoptosis and cell proliferation. This study advances the understanding of herbal therapies for osteoporosis and offers a framework for discovering novel therapeutic agents. Full article

Abstract: This study focuses on the characterization and re-engineering of glucose transport in β-galactosidase (BglD) to enhance its catalytic efficiency. Computational prediction methods were employed to identify key residues constituting access tunnels for lactose and glucose, revealing distinct pockets for both substrates. In silico simulated saturation mutagenesis of residues T215 and T473 led to the identification of eight mutant variants exhibiting potential enhancements in glucose transport. Site-directed mutagenesis at T215 and T473 resulted in mutants with consistently enhanced specific activities, turnover rates, and catalytic efficiencies. These mutants also demonstrated improved galactooligosaccharide (GOS) synthesis, yielding an 8.1–10.6% enhancement over wild-type BglD yield. Structural analysis revealed that the mutants exhibited transformed configurations and localizations of glucose conduits, facilitating expedited glucose release. This study’s findings suggest that the re-engineered mutants offer promising avenues for enhancing BglD’s catalytic efficiency and glucose translocation, thereby improving GOS synthesis. By-product (glucose) re-tunneling is a viable approach for enzyme tunnel engineering and holds significant promise for the molecular evolution of enzymes. Full article

Background: Hypofunction of the glutamate system in the brain is one of the pathophysiological hypotheses for schizophrenia. Accumulating animal and clinical studies show that sarcosine (N-methylglycine), a glycine transporter-1 inhibitor, is effective in ameliorating the negative and cognitive symptoms of schizophrenia. The aims of the present study were to observe the effects of sarcosine on neuronal activity in the dorsal CA1 (dCA1) hippocampal neurons within an NMDA receptor hypofunction model induced by MK801. Methods: We applied in vivo calcium imaging to observe the dynamics of fluorescence from the dCA1 hippocampal neurons when the mice were exploring in an open field. Using this tool, we directly measured and compared neuronal properties between sarcosine-treated and untreated mice. At the same time, the physiological function of the neurons was also quantified by measuring their place fields. Results: Our data demonstrated that MK-801 (0.2 mg/kg) diminished the fluorescence intensity of dCA1 neurons that had been genetically modified with a calcium indicator. MK-801 also significantly increased the correlation coefficient between the fluorescence dynamics of pairs of cells, a feature that may be linked to the symptom of disorganization in human patients with schizophrenia. The spatial correlations of place fields in the mice were impaired by MK-801 as well. Injected sarcosine (500 mg or 1000 mg/kg) significantly alleviated the abovementioned abnormalities. Conclusions: Our data provide evidence to support the use of sarcosine to alleviate symptoms of schizophrenia, especially hippocampus-related functions. Full article

This paper examines the essential role of urban green spaces in fostering healthy living from a landscape architecture perspective. Health goes beyond the mere absence of disease to include physical, mental, and social wellbeing, all of which are greatly enhanced by accessible green spaces. By synthesising existing literature, this paper shows that urban green spaces have strong positive associations with health outcomes, especially in urban settings where environmental stressors are pronounced. The paper stresses the importance of designing attractive and accessible green spaces that encourage physical activity, mental wellbeing, and social interaction, addressing public health issues such as obesity and mental health disorders. In addition to physical and mental health benefits, the paper explores the potential of local food production through edible green infrastructure, such as community gardens, which can significantly improve diet and nutrition. Additionally, the study discusses disparities in the access to quality green spaces, particularly between the Global North and South, and advocates for equitable design strategies that serve diverse populations. Integrating evidence-based approaches into landscape architecture, the paper argues for the establishment of urban green spaces as essential elements of public health infrastructure. Finally, the paper calls for future research and policy efforts to maximise the health benefits of urban green spaces and improve the quality of life in urban environments. Full article

The fourth-order nonlinear Boussinesq water wave equation, which describes the propagation of long waves in the intertidal zone, is investigated in this study. The exact wave patterns of the equation were computed using the $tanh$ method. As stability decreased, soliton wave structures were derived using similarity transformations. Numerical simulations supported these findings. The $tanh$ method introduced a Galilean modification, leading to the discovery of several new exact solutions. Subsequently, the fourth-order nonlinear Boussinesq wave equation was transformed into a planar dynamical system using the travelling wave transformation. The quasi-periodic, cyclical, and nonlinear behaviors of the analyzed equation were particularly examined. Numerical simulations revealed that varying the physical parameters impacts the system’s nonlinear behavior. Graphs represent all possible examples of phase portraits in terms of these parameters. Furthermore, the study was proven to be highly beneficial for addressing issues such as shock waves and highly active travelling wave processes. Sensitivity analysis theory and the Lyapunov exponent were employed, offering a wide variety of linear periodic and first-frequency periodic characteristics. Sensitivity analysis and multistability analysis of the Boussinesq water wave equation were thoroughly investigated. Full article

The use of high catalyst loading is required for most of the organocatalyzed asymmetric aldol reactions in organic synthesis, and this often presents challenges during purification and difficulties in catalyst recovery from the reaction mixture. The immobilization of the catalyst onto gold nanoparticles (AuNPs) can change the structural conformations of the catalyst, thereby improving its catalytic activity and reusability. Herein we report on the synthesis of aldolase mimetic peptide coupled to gold nanoparticles (AuNPs) as efficient organocatalysts for asymmetric aldol reaction. AuNPs were synthesized using the Turkevich method. The conjugation of the peptide to AuNPs was characterized using surface plasmon resonance (SPR), Raman and X-ray photoelectron spectroscopy, and transmission electron microscopy (TEM) was used for particle size determination. The produced nanoparticles, whose sizes depended on the reduction method, were quasi-spherical with a relatively narrow size distribution. The peptide–AuNP conjugates were evaluated for aldol reaction catalytic activity between carbonyls p-nitrobenzaldehyde and cyclohexanone. The products were obtained with good yields (up to 85%) and enantioselectivity (up to 94%). The influence of organic solvents, pH and buffer solutions was also investigated. The results showed that the buffer solutions regulated the colloidal stability of AuNPs, resulting in a significant enhancement in the catalytic rate of the peptide–AuNP conjugate. Full article

The classical function of the mineralocorticoid receptor (MR) is to maintain electrolytic homeostasis and control extracellular volume and blood pressure. The MR is expressed in the central nervous system (CNS) and is involved in the regulation of the hypothalamic–pituitary–adrenal (HPA) axis as well as sleep physiology, playing a role in the non-rapid eye movement (NREM) phase of sleep. Some patients with psychiatric disorders have very poor sleep quality, and a relationship between MR dysregulation and this disorder has been found in them. In addition, the MR is involved in the regulation of the renal peripheral clock. One of the most common comorbidities observed in patients with chronic kidney disease (CKD) is poor sleep quality. Patients with CKD experience sleep disturbances, including reduced sleep duration, sleep fragmentation, and insomnia. To date, no studies have specifically investigated the relationship between MR activation and CKD-associated sleep disturbances. However, in this review, we analyzed the environment that occurs in CKD and proposed two MR-related mechanisms that may be responsible for these sleep disturbances: the circadian clock disruption and the high levels of MR agonist observed in CKD. Full article

The mutational drift of SARS-CoV-2 and the appearance of multiple variants, including the latest Omicron variant and its sub-lineages, has significantly reduced (and in some cases abolished) the protective efficacy of Wuhan spike-antigen-based vaccines and therapeutic antibodies. One of the most functionally constrained and thus largely invariable regions of the spike protein is the one involved in the interaction with the ACE2 receptor mediating the cellular entry of SARS-CoV-2. Engineered ACE2, both as a full-length protein or as an engineered polypeptide fragment, has been shown to be capable of preventing the host-cell binding of all viral variants and to be endowed with potent SARS-CoV-2 neutralization activity both in vitro and in vivo. Here, we report on the biochemical and antiviral properties of rationally designed ACE2 N-terminal, three-helix fragments that retain a native-like conformation. One of these fragments, designated as PRP8_3H and produced in recombinant form, bears structure-stabilizing and binding-affinity enhancing mutations in a-helix-I and in both a-helix I and II, respectively. While the native-like, unmodified three a-helices ACE2 fragment proved to be thermally unstable and without any detectable pseudovirion neutralization capacity, PRP8_3H was found to be highly thermostable and capable of binding to the SARS-CoV-2 spike receptor-binding domain with nanomolar affinity and to neutralize both Wuhan and Omicron spike-expressing pseudovirions at (sub)micromolar concentrations. PRP8_3H thus lends itself as a highly promising ACE2 decoy prototype suitable for a variety of formulations and prophylactic applications. Full article

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by a single mutation in the huntingtin gene (HTT). Normal HTT has a CAG trinucleotide repeat at its N-terminal within the range of 36. However, once the CAG repeats exceed 37, the mutant gene (mHTT) will encode mutant HTT protein (mHTT), which results in neurodegeneration in the brain, specifically in the striatum and other brain regions. Since the mutation was discovered, there have been many research efforts to understand the mechanism and develop therapeutic strategies to treat HD. HTT is a large protein with many post-translational modification sites (PTMs) and can be modified by phosphorylation, acetylation, methylation, sumoylation, etc. Some modifications reduced mHTT toxicity both in cell and animal models of HD. We aimed to find the known kinase inhibitors that can modulate the toxicity of mHTT. We performed an in vitro kinase assay using HTT peptides, which bear different PTM sites identified by us previously. A total of 368 kinases were screened. Among those kinases, cyclin-dependent kinases (CDKs) affected the serine phosphorylation on the peptides that contain S1181 and S1201 of HTT. We explored the effect of CDK1 and CDK5 on the phosphorylation of these PTMs of HTT and found that CDK5 modified these two serine sites, while CDK5 knockdown reduced the phosphorylation of S1181 and S1201. Modifying these two serine sites altered the neuronal toxicity induced by mHTT. Roscovitine, a CDK inhibitor, reduced the p-S1181 and p-S1201 and had a protective effect against mHTT toxicity. We further investigated the feasibility of the use of roscovitine in HD mice. We confirmed that roscovitine penetrated the mouse brain by IP injection and inhibited CDK5 activity in the brains of HD mice. It is promising to move this study to in vivo for pre-clinical HD treatment. Full article

Pigeon pea (Cajanus cajan (L.) Millsp.), a potential legume as an economic source of protein, is commonly cultivated in tropical and subtropical regions of the world. It possesses medicinal properties and acts as a cash crop, benefiting low-income farmers economically. The identification of pigeon peas exhibiting drought tolerance has become crucial in addressing water scarcity issues in the agriculture sector. In addition, exploring the genetic diversity among genotypes is important for conservation, management of genetic resources, and breeding programs. The aim of this study was to evaluate the morpho-physiological and biochemical responses of selected pigeon pea genotypes under pot-induced water stress conditions through different field capacities as well as the genetic diversity using start codon targeted (SCoT) markers. A significant variation was observed for the physiological traits studied. The accumulation of fresh weight (FW) and dry weight (DW) was significantly reduced in moderate and severe drought stress conditions. The lowest % DW decrease was found in LM (35.39%), KAT (39.43%), and SM (46.98%) than other genotypes at severe drought stress. Analyses of physiological responses including the photosynthetic efficiency (Phi2), the chlorophyll content (SPAD), and the relative water content (RWC) revealed positive and negative correlations with various parameters, reflecting the impact of drought stress on the chlorophyll content. The results revealed that biochemical traits including the total phenolic content, soluble sugars, proline, total protein, total amino acids, and free amino acids were variably and significantly increased under water stress. Antioxidant enzyme activity levels, specifically ascorbate peroxidase (APX) and catalase, varied among the genotypes and in response to severe water stress, offering further insights into adaptive responses. The eight genotypes analysed by use of 20 SCoT markers revealed 206 alleles and an average of 10.3 alleles per locus. Genetic similarity ranged from 0.336 to 0.676, clustering the pigeon pea genotypes into two major groups by the unweighted pair group method of arithmetic averages (UPGMA) cluster analysis. Principal coordinate analysis (PCoA) explained 43.11% of genetic variation and based on analysis of molecular variance, a high genetic variation (80%) within populations was observed, emphasizing the potential for genetic improvement. Among the eight genotypes studied, LM and KAT were drought tolerant and genetically diverse and therefore could be used as parents for developing drought tolerance in pigeon pea. Full article

Known for their compact size, mobility, and off-road capabilities, motorcycles are increasingly used for logistics, emergency rescue, and reconnaissance. However, due to their two-wheeled nature, motorcycles are susceptible to instability, heightening the risk of tipping during cornering. This study includes some research and exploration into the following aspects: (1) The design of a front-wheel steering self-balancing controller. It achieves self-balance during motion by adjusting the front-wheel steering angle through manipulation of handlebar torque. (2) Trajectory tracking control based on preview control theory. It establishes a proportional relationship between lateral deviation and lean angle, as determined by path preview. The desired lean angle then serves as input for the self-balancing controller. (3) A pre-braking controller for enhanced active safety. To prevent lateral slide on wet and slippery surfaces, the controller is designed considering the motorcycle’s maximum braking deceleration. These advancements were validated via a joint BikeSim and Matlab/Simulink simulation, which included scenarios such as double lane changes and 60 m-radius turns. The results demonstrate that the intelligent motorcycle equipped with the proposed control algorithm tracks trajectories and maintains stability effectively. Full article

The expression of FKBP5, and its resulting protein FKBP51, is strongly induced by glucocorticoids. Numerous studies have explored their involvement in a plethora of cellular processes and diseases. There is, however, a lack of knowledge on the role of the different RNA splicing variants and the two protein isoforms, one missing functional C-terminal motifs. In this study, we use in vitro models (HeLa and Jurkat cells) as well as peripheral blood cells of a human cohort (N = 26 male healthy controls) to show that the two expressed variants are both dynamically upregulated following dexamethasone, with significantly earlier increases (starting 1–2 h after stimulation) in the short isoform both in vitro and in vivo. Protein degradation assays in vitro showed a reduced half-life (4 h vs. 8 h) of the shorter isoform. Only the shorter isoform showed a subnuclear cellular localization. The two isoforms also differed in their effects on known downstream cellular pathways, including glucocorticoid receptor function, macroautophagy, immune activation, and DNA methylation regulation. The results shed light on the difference between the two variants and highlight the importance of differential analyses in future studies with implications for targeted drug design. Full article