Royal Society Open Science最新文献

Inflammation is a complex physiological response associated with the onset and progression of various disorders, including diabetes. In this study, we synthesized a series of diclofenac acid derivatives and evaluated their potential anti-diabetic and anti-inflammatory activities. The compounds were specifically assessed for their ability to inhibit 15-lipoxygenase (15-LOX) and α-glucosidase enzymes. The structures of synthesized derivatives were confirmed through ¹H nuclear magnetic resonance (NMR), ¹³C-NMR and high-resolution mass spectrometry (electron ionization) analysis. All these synthesized derivatives exhibited varying degrees of inhibitory activity against LOX, when compared with standard drugs, compounds 5a (half-maximal inhibitory concentration (IC₅₀) 14 ± 1 µM), 5b (IC₅₀ 61 ± 1 µM) and 7c (IC₅₀ 67 ± 1 µM) showed good activity against the LOX enzyme. While the α-glucosidase inhibitory results revealed that most of the compounds exhibited significant activity when compared with the standard drug acarbose (376 ± 1 µM). The most potent compounds as α-glucosidase inhibitors were 7b (3 ± 1 µM), 4b (5 ± 1 µM), 7a (7 ± 1 µM) and 8b (11 ± 1 µM). All these active compounds were found to be least toxic and maintained the mononuclear cells viability at 96-97% compared with that of controls as determined by multi-transaction translator assay. Molecular docking studies further reiterated the significance of these 'lead' compounds with great potential against the target enzymes in the process of drug discovery.

Event segmentation is a neurocognitive process bridging perception and episodic memory. To our knowledge, almost all segmentation work is framed towards humans, yet evolutionarily conserved mechanisms in event cognition exist across species. Here, we addressed segmentation in a way that is applicable to humans and non-human animals, inspired by research in rats; specifically, the fragmentation of grid-cell spatial representations following the insertion of boundaries into an environment (forming a corridor maze). Participants indicated when they felt a meaningful unit of activity ended and another began, while watching an agent traverse from a first-person perspective. A virtual corridor maze (experiment 1) and two other mazes were used (experiment 2), with participants viewing/segmenting the same stimuli twice. We found that people segmented more during turns relative to corridors, with elevated segmentation occurring in discrete moments around turns. Interestingly, we also found that boundaries of the corridor maze facilitated an increase in segmentation within and across viewings. These results suggest that segmentation can be driven by recognized repeating activity that can become more meaningful over time, highlighting an important link between event segmentation and pattern separation that is relevant to many species in their formation of episodic-(like) memory.

We develop a Huntington's disease (HD) progression model and integrate this with a novel economic model, accounting for the major factors of the HD's societal cost. Data from the Enroll-HD observational study were used to fit a continuous-time hidden Markov disease progression model, which identified five distinct states. The number of disease states was determined using a cross-validated maximum likelihood approach. A novel data augmentation method was used to correct the biased life expectancy of the progression model. Multiple sources of cost data were then mapped to Enroll-HD variables using expert experience. A simulation of a synthetic patient population was used to show the feasibility of the approach in estimating population costs and the impact of hypothetical intervention scenarios. Our results confirm that early cognitive decline, which is not captured by the total functional capacity score currently used by clinicians but flagged up in HD integrated staging system, can be quantified from participants' visits. Finally, the results of the UK cost modelling show that indirect costs of HD such as state benefits and lost gross domestic product contribution could be the driving factors for the societal cost, over and above health and social care costs.

When analysing the effect of negative temperature on overwintering pit constructions of unsaturated soil, using the mechanical parameter of saturated soil at room temperature leads to an inaccuracy in the research findings. The strength parameters are obtained through indoor experiments. The foundation pit model is created using FLAC3D numerical simulation software based on the indoor experimental data. The influence of different parameters on the stress and deformation of the overwintering deep foundation pit supporting structure is analysed. The numerical simulation results obtained are compared with the actual monitoring data. According to research, the matric suction of the silty clay in its natural state in the Changchun area is 70 kPa. As the temperature decreases, the total cohesion of the unsaturated soil increases, and the internal friction angle tends to decrease. The numerical simulation results are consistent with the actual monitoring data changes. With the excavation, the horizontal displacement of the supporting structure increases first and then decreases, reaching the maximum displacement at two-thirds of the foundation pit. Compared with room temperature, the deformation of the supporting structure is larger under a negative temperature condition. The deformation of the supporting structure simulated by the actual temperature mechanical parameters is larger than that under the condition of normal temperature mechanical parameters. The frost-heaving force increases with the overall excavation, and a surge occurs at the bottom of the pit. The frost-heaving force changes most significantly under the condition of freezing at -20°C for 30 days.

This work reports a detailed theoretical study of the molecular parameters, harmonic vibrational frequencies, UV absorption spectra and standard enthalpies of formation for the radicals C₂X₃ (with X = F, Cl and Br) and a comparison with the corresponding determinations for the rest of the members of the family C₂X _n (with n = 2-4). Molecular properties were calculated using different levels of theory: density functional theory employing the B3LYP, X3LYP, BMK, M06-2X and M08-HX functionals combined with the basis sets 6-311++G(3df,3pd) and aug-cc-pVTZ, and the ab initio composite models G3B3 and G4. Structural and spectroscopic characterization of the C₂F₃, C₂Cl₃ and C₂Br₃ radicals, along with the estimation of the enthalpies of formation of C₂F₃ and C₂Cl₃, were derived here for the first time, to our knowledge. In particular, values of -220.9 ± 2.9, 230.8 ± 3.8 and 375.4 ± 5.9 kJ mol^-1 were computed for enthalpies of formation of C₂F₃, C₂Cl₃ and C₂Br₃, respectively. Additionally, enthalpies of formation for related closed-shell molecules were obtained with less uncertainty compared to those found in the literature. The recommended values of -669.6 ± 3.8, -23.0 ± 4.6 and 155.3 ± 5.0 kJ mol^-1 were derived for C₂F₄, C₂Cl₄ and C₂Br₄, while corresponding values of 0.6 ± 6.3, 228.1 ± 2.1 and 319.6 ± 5.4 kJ mol^-1 were estimated for C₂F₂, C₂Cl₂ and C₂Br₂, respectively.

In this study, we investigate the impact of demographic characteristics on Middle East respiratory syndrome coronavirus (MERS-CoV) cases in Saudi Arabia, specifically focusing on the time intervals between symptom onset and key events such as hospitalization, case confirmation, reporting and death. We estimate these intervals using data from 2196 cases occurring between June 2012 and January 2020, partitioning the data into four age groups (0-24 years, 25-49 years, 50-74 years and 75-100 years). The duration from symptom onset to hospitalization varies between age cohorts, ranging from 4.03 to 4.75 days, with the 75-100 age group experiencing the longest delay. The interval from symptom onset to case confirmation spans 5.83-8.24 days, and again, the 75-100 age group faces the lengthiest delay. The interval from symptom onset and case reporting ranges from 7.0 to 9.8 days, with the 75-100 age group experiencing the longest delay. The period from symptom onset to death varies across age groups (12.3-16.1 days), with elevated mortality rates during outbreaks. Importantly, we observe age-based differences in the risk of hospitalization and other measures of infection severity, including the probability of death conditional on hospitalization. Careful quantification of epidemiological characteristics, including inference of key epidemiological periods and assessments of differences between cases of different ages, plays a crucial role in understanding the progression of MERS-CoV outbreaks and formulating effective public health strategies to mitigate their impact.

In the wake of the COVID-19 pandemic, many journals swiftly changed their editorial policies and peer-review processes to accelerate the provision of knowledge about COVID-related issues to a wide audience. These changes may have favoured speed at the cost of accuracy and methodological rigour. In this study, we compare 100 COVID-related articles published in four major psychological journals between 2020 and 2022 with 100 non-COVID articles from the same journal issues and 100 pre-COVID articles published between 2017 and 2019. Articles were coded with regard to design features, sampling and recruitment features, and openness and transparency practices. Even though COVID research was, by and large, more 'observational' in nature and less experimentally controlled than non- or pre-COVID research, we found that COVID-related studies were more likely to use 'stronger' (i.e. more longitudinal and fewer cross-sectional) designs, larger samples, justify their sample sizes based on a priori power analysis, pre-register their hypotheses and analysis plans and make their data, materials and code openly available. Thus, COVID-related psychological research does not appear to be less rigorous in these regards than non-COVID research.

In animal models, social isolation impacts threat responding and threat learning, especially during development. This study examined the effects of acute social isolation on threat learning in human adolescents using an experimental, within-participant design. Participants aged 16-19 years underwent a session of complete isolation and a separate session of isolation with virtual social interactions, counterbalanced between participants, as well as a baseline session. At baseline and following each isolation session, participants reported their psychological state and completed a threat learning task in which self-report ratings and physiological responses to learned threat and safety cues were measured. Threat learning increased after both isolation sessions in two ways. First, participants found the learned threat cue more anxiety-inducing and unpleasant after isolation compared with baseline. Second, during threat extinction, electrodermal activity was partially elevated after isolation compared with baseline. Further, the results suggested that isolation influenced threat learning through state loneliness. Threat learning is central to threat-related disorders including anxiety, phobias, obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD), and our findings suggest that isolation and loneliness in adolescence might increase vulnerability to the emergence of these disorders through increased threat learning.

We present the first comprehensive study for signal growth in transmission lines (TL) with purely time-modulated characteristic impedance $Z_o$ (infinite superluminality). This study pioneers the investigation into the effects of varying the cell's electrical length and the impact of loss on momentum bandgaps and amplification levels. It also thoroughly examines how time-modulated transmission line truncation by a static load influences the sensitivity of amplification gain to the relative phase between the incoming signal and modulation, comparing these findings with the case of parametric amplification. Varying $Z_o$ is accomplished by loading TLs with a sinusoidally time-modulated capacitor (TMC). The study starts with a simple lumped model cell to facilitate understanding of the phenomena. Following this, transmission lines are introduced, and the effects of incorporating loss are examined. To accomplish this, three models are investigated: a lossless L-C TL lumped model loaded with a shunt lossless TMC and a TL loaded with a shunt lossless and lossy TMC. Dispersion diagrams are plotted and momentum bandgaps are identified at a modulation frequency double the signal frequency. Within the momentum bandgap, only imaginary frequencies are found and correlated to momentum bandgap width and signal growth level. Signal growth is confirmed using harmonic balance and transient simulations, and the results are consistent with the dispersion diagram outcomes.

Free will is assumed to be the core of an individual's self-concept. Belief in free will has been studied extensively and was found to be correlated with many behavioural and psychological outcomes. Although developed and validated in the West, the Free will and Determinism Plus (FAD-Plus) scale has been translated, used, and interpreted as a measurement of free will beliefs in multiple cultures. However, the cross-cultural measurement invariance of FAD-Plus has not been examined. Given the cultural differences in understanding the concept of 'free will', items of FAD-Plus may have different interpretations in different cultures, which may compromise its cross-cultural measurement invariance. To provide empirical evidence for the lack of cross-cultural measurement invariance, we collected data in China and analyzed these data together with open datasets of FAD-Plus in three other languages: Japanese, French and English. We only found partial measurement invariance between the Chinese and English datasets, as well as the Japanese and English datasets. These results provided the first assessment of cross-cultural measure invariance of FAD-Plus. We discussed the potential implications of the current study for future studies in the field.