Miracle-dz/UniFAR-FTUs huggingface dataset:
In Vitro and In Vivo Pharmaco-Toxicological Characterization of 1-Cyclohexyl-x-methoxybenzene Derivatives in Mice: Comparison with Tramadol and PCP

1-cyclohexyl-x-methoxybenzene is a novel psychoactive substance (NPS), first discovered in Europe in 2012 as unknown racemic mixture of its three stereoisomers: ortho, meta and para. Each of these has structural similarities with the analgesic tramadol and the dissociative anesthetic phencyclidine. In light of these structural analogies, and based on the fact that both tramadol and phencyclidine are substances that cause toxic effects in humans, the aim of this study was to investigate the in vitro and in vivo pharmacodynamic profile of these molecules, and to compare them with those caused by tramadol and phencyclidine. In vitro studies demonstrated that tramadol, ortho, meta and para were inactive at mu, kappa and delta opioid receptors. Systemic administration of the three stereoisomers impairs sensorimotor responses, modulates spontaneous motor activity, induces modest analgesia, and alters thermoregulation and cardiorespiratory responses in the mouse in some cases, with a similar profile to that of tramadol and phencyclidine. Naloxone partially prevents only the visual sensorimotor impairments caused by three stereoisomers, without preventing other effects. The present data show that 1-cyclohexyl-x-methoxybenzene derivatives cause pharmaco-toxicological effects by activating both opioid and non-opioid mechanisms and suggest that their use could potentially lead to abuse and bodily harm.
AACCI Approved Methods Technical Committee Report: A New AACCI Approved Method (32-24.01) for Measuring Viscosity of β-Glucan in Cereal Products Using the Rapid Visco Analyzer

Regulations allowing health claims linking consumption of food products rich in β-glucan with reduced risk of coronary heart disease have increased the interest of food companies and consumers in such products as healthy food options. Oat and barley cereal products, in particular, have garnered attention due to their high β-glucan contents. Processing oat and barley into food products may affect the physicochemical characteristics of β-glucan and subsequently its physiological effects, however. A new proposed AACCI Approved Method (32-24.01) using RVA to measure β-glucan viscosity in cereal products has been developed and validated. The objective of this method is to determine the viscosity of β-glucan that is soluble under simulated digestion conditions without requirements for pretreatments of cereal products. This viscosity measurement is obtained by mixing an aqueous suspension of ground sample with digestive enzymes in a disposable canister in the RVA. The method can be used by laboratories as a scre.
A Multicentre, Randomised, Controlled Trial of a Combined Clinical Treatment for First-Episode Psychosis

Introduction: There is evidence that early intervention contributes to improving the prognosis and course of first-episode psychosis (FEP). However, further randomised treatment clinical trials are needed. Objectives: The aim of this study was to compare the efficacy of a combined clinical treatment involving Cognitive Behavioural Therapy (CBT) as an adjunctive to treatment-as-usual (TAU) (CBT+TAU) versus TAU alone for FEP. Patients and methods: In this multicentre, single-blind, randomised controlled trial, 177 participants were randomly allocated to either CBT+TAU or TAU. The primary outcome was post-treatment patient functioning. Results: The CBT+TAU group showed a greater improvement in functioning, which was measured using the Global Assessment Functioning (GAF) and Functioning Assessment Short Test (FAST), compared to the TAU group post-treatment. The CBT+TAU participants exhibited a greater decline in depressive, negative, and general psychotic symptoms; a better awareness of the disease and treatment adherence; and a greater increase in brain-derived neurotrophic factor levels than TAU participants. Conclusions: Early intervention based on a combined clinical treatment involving CBT as an adjunctive to standard treatment may improve clinical and functional outcomes in FEP.
Assay for heavy metals using an inhibitive assay based on the acetylcholinesterase from Pangasius hypophthalmus (Sauvage, 1878)

Acetylcholinesterase (AChE) is generally used as an inhibitive assay for insecticides. A lesser-known property of AChE is its inhibition by heavy metals. In this work, we evaluate an AChE from silver catfish brain (Pangasius sp.), wasted from aquaculture industry, as an inhibitive assay for heavy metals. We discovered that the AChE was completely inhibited by Cr6+, Ag 2+, Cd2+, Hg2+, Cu2+, Zn 2+ and Pb2+ during an initial screening. When testing at various concentrations, the above heavy metals exhibited exponential decay type inhibition curves. The calculated IC50 for Hg2+, Cu 2+, Ag , Cr6+, Cd2+, Pb2+, and Zn2+were 0.071, 0.088, 0.088, 0.87, 0.913, 1.1, and 1.572 mg/L, respectively. The Limit of Detection LOD and Limit of Quantification LOQ values of the heavy metals are within the range of the Maximum Permissibility Limit MPL allowed by the Malaysian Department of Environment DOE for Class-Ill rivers. The IC50 values for these heavy metals are comparable, and some are lower than those of the currently known assays, such as immobilised urease, Daphnia magna, Microtox™, rainbow trout, papain and bromelain assays. Field trial works on an industrial drainage site had shown that the developed assay is applicable in detecting heavy metals in the water. The assay can be carried out in less than 30 min under ambient temperature.
Curcumin Potentiates α7 Nicotinic Acetylcholine Receptors and Alleviates Autistic-Like Social Deficits and Brain Oxidative Stress Status in Mice

Autistic spectrum disorder (ASD) refers to a group of neurodevelopmental disorders characterized by impaired social interaction and cognitive deficit, restricted repetitive behaviors, altered immune responses, and imbalanced oxidative stress status. In recent years, there has been a growing interest in studying the role of nicotinic acetylcholine receptors (nAChRs), specifically α7-nAChRs, in the CNS. Influence of agonists for α7-nAChRs on the cognitive behavior, learning, and memory formation has been demonstrated in neuro-pathological condition such as ASD and attention-deficit hyperactivity disorder (ADHD). Curcumin (CUR), the active compound of the spice turmeric, has been shown to act as a positive allosteric modulator of α7-nAChRs. Here we hypothesize that CUR, acting through α7-nAChRs, influences the neuropathology of ASD. In patch clamp studies, fast inward currents activated by choline, a selective agonist of α7-nAChRs, were significantly potentiated by CUR. Moreover, choline induced enhancement of spontaneous inhibitory postsynaptic currents was markedly increased in the presence of CUR. Furthermore, CUR (25, 50, and 100 mg/kg, i.p.) ameliorated dose-dependent social deficits without affecting locomotor activity or anxiety-like behaviors of tested male Black and Tan BRachyury (BTBR) mice. In addition, CUR (50 and 100 mg/kg, i.p.) mitigated oxidative stress status by restoring the decreased levels of superoxide dismutase (SOD) and catalase (CAT) in the hippocampus and the cerebellum of treated mice. Collectively, the observed results indicate that CUR potentiates α7-nAChRs in native central nervous system neurons, mitigates disturbed oxidative stress, and alleviates ASD-like features in BTBR mice used as an idiopathic rodent model of ASD, and may represent a promising novel pharmacological strategy for ASD treatment.
Chemical Profile, Antioxidant Capacity, and Antimicrobial Activity of Essential Oils Extracted from Three Different Varieties (Moldoveanca 4, Vis Magic 10, and Alba 7) of Lavandula angustifolia

Chemical composition, antioxidant capacity, and antimicrobial activity of lavender essential oils (LEOs) extracted from three different varieties of Lavandula angustifolia Mill. (1-Moldoveanca 4, 2-Vis magic 10, and 3-Alba 7) have been determined. These plants previously patented in the Republic of Moldova were cultivated in an organic agriculture system in the northeastern part of Romania and then harvested in 3 consecutive years (2017–2019) to obtain the essential oils. From the inflorescences in the complete flowering stage, the LEOs were extracted by hydrodistillation. Then, their composition was analyzed by gas chromatography coupled with mass spectrometry (GC-MS) and by Fourier Transformed Infrared spectroscopy (FT-IR). The major identified constituents are as follows: linalool (1: 32.19–46.83%; 2: 29.93–30.97%; 3: 31.97–33.77%), linalyl acetate (1: 17.70–35.18%; 2: 27.55–37.13%; 3: 28.03–35.32%), and terpinen-4-ol (1: 3.63–7.70%; 2: 3.06–7.16%; 3: 3.10–6.53%). The antioxidant capacity as determined by ABTS and DPPH assays indicates inhibition, with the highest activity obtained for LEO var. Alba 7 from 2019. The in vitro antimicrobial activities of the LEOs and combinations were investigated as well, by using the disk diffusion method and minimum inhibitory concentration (MIC) against the Gram-positive bacterial strain Staphylococcus aureus (ATCC 6538), Gram-negative Pseudomonas aeruginosa (ATCC 27858), Escherichia coli (ATCC 25922), the yeast Candida albicans (ATCC 10231), and clinical isolates. Our results have shown that LEOs obtained from the three studied varieties of L. angustifolia manifest significant bactericidal effects against tested microorganisms (Staphylococcus aureus and Escherichia coli), and antifungal effects against Candida albicans. The mixture of LEOs (Var. Alba 7) and geranium, respectively, in tea tree EOs, in different ratios, showed a significant enhancement of the antibacterial effect against all the studied strains, except Pseudomonas aeruginosa.
The salience of choice fuels independence: Implications for self-perception, cognition, and behavior

Significance These studies find that choice—an increasingly salient feature of many cultural contexts—is linked with an array of previously undocumented behavioral consequences. When people think of their actions as choices, they feel larger and stronger than others, are attracted to ideas of independence, and feel empowered to voice their opinions. Choosing what to eat and which shampoo to buy may seem like trivial acts, yet the current research finds that the salience of choice alone can have a range of powerful psychological effects. As the ideas and practices of choice become increasingly salient worldwide, they will likely fuel a host of unanticipated consequences, including a sense of self as independent, and so contribute to the rise of global individualism. More than ever before, people across the world are exposed to ideas of choice and have opportunities to make choices. What are the consequences of this rapidly expanding exposure to the ideas and practice of choice? The current research investigated an unexamined and potentially powerful consequence of this salience of choice: an awareness and experience of independence. Four studies (n = 1,288) across three cultural contexts known to differ in both the salience of choice and the cultural emphasis on independence (the United States, Singapore, and India) provided converging evidence of a link between the salience of choice and independence. Singaporean students who recalled choices rather than actions represented themselves as larger than their peers (study 1). Conceptually replicating this finding, study 2 found that Americans who recalled choices rather than actions rated themselves as physically stronger. In a word/nonword lexical decision task (study 3), Singaporean students who recalled choices rather than actions were quicker at identifying independence-related words, but not neutral or interdependence-related words. Americans, Singaporeans, and Indians all indicated that when working in an organization that emphasized choice, they would be more likely to express their opinions. Similarly, Americans, Singaporeans, and Indians reported a preference for working in such an organization (studies 4a and 4b). The findings suggest that the salience of personal choice may drive an awareness and experience of independence even in contexts where, unlike in the United States, independence has not been the predominant ethos. Choice may be an unmarked and proximate mechanism of cultural change and growing global individualism.
The Transformational Experience of Junior Nurses Resulting from Providing Care to COVID-19 Patients: From Facing Hurdles to Achieving Psychological Growth

The rapid spread of coronavirus disease 2019 (COVID-19) has put significant pressure on junior nursing staff. The objective of this study was to examine the in-depth experiences of junior nurses in providing care for COVID-19 patients within an acute care setting. This study employed a phenomenological method to understand the situation from a first-person perspective. Purposive sampling was used. Interviews were performed with 40 junior nurses (<4 years of clinical experience) who provided direct care to COVID-19 patients in isolation wards in acute care settings in Hong Kong. The interviews were conducted from 1 January 2021 to 24 May 2021 via virtual conferencing software (Zoom) to maintain social distancing, and the responses were analysed using Colaizzi’s seven-step method. Junior nurses’ psychological experiences of providing direct care to COVID-19 patients were categorised into four main themes. First, there were hurdles in the early stages, in which participants experienced negative emotions, such as fear, anxiety, helplessness, and fatigue. Somatic symptoms, such as headaches and sleep disturbance, were reported. Second, the adoption of self-care coping strategies enabled nurses to confront the hurdles, signifying the start of self-transformation. Third, junior nurses maintained positivity under pressure by appreciating their sources of support (including their families and other important relationships in their lives). Professionalism was also found to reinforce positivity. Fourth, self-transformation resulted in psychological growth, which prepared junior nurses to be resilient and confident in their clinical practice to take up future challenges in the ongoing battle against the pandemic. The hurdles experienced by junior nurses at the early stage of their work in isolation wards provided the foundation upon which self-transformation took place. Being able to employ self-care coping strategies and further sustain positivity characterised the self-transformation process. Eventually, junior nurses became resilient and more capable of understanding both the negativity and positivity of their experiences. The self-transformation process also enabled junior nurses to recognise and appreciate the wider support system from various parties in society.
New Partners Identified by Mass Spectrometry Assay Reveal Functions of NCAM2 in Neural Cytoskeleton Organization

Neuronal cell adhesion molecule 2 (NCAM2) is a membrane protein with an important role in the morphological development of neurons. In the cortex and the hippocampus, NCAM2 is essential for proper neuronal differentiation, dendritic and axonal outgrowth and synapse formation. However, little is known about NCAM2 functional mechanisms and its interactive partners during brain development. Here we used mass spectrometry to study the molecular interactome of NCAM2 in the second postnatal week of the mouse cerebral cortex. We found that NCAM2 interacts with >100 proteins involved in numerous processes, including neuronal morphogenesis and synaptogenesis. We validated the most relevant interactors, including Neurofilaments (NEFs), Microtubule-associated protein 2 (MAP2), Calcium/calmodulin kinase II alpha (CaMKIIα), Actin and Nogo. An in silico analysis of the cytosolic tail of the NCAM2.1 isoform revealed specific phosphorylation site motifs with a putative affinity for some of these interactors. Our results expand the knowledge of NCAM2 interactome and confirm the key role of NCAM2 in cytoskeleton organization, neuronal morphogenesis and synaptogenesis. These findings are of interest in explaining the phenotypes observed in different pathologies with alterations in the NCAM2 gene.
A Regulator Based “Semi-Targeted” Approach to Activate Silent Biosynthetic Gene Clusters

By culturing microorganisms under standard laboratory conditions, most biosynthetic gene clusters (BGCs) are not expressed, and thus, the products are not produced. To explore this biosynthetic potential, we developed a novel “semi-targeted” approach focusing on activating “silent” BGCs by concurrently introducing a group of regulator genes into streptomycetes of the Tübingen strain collection. We constructed integrative plasmids containing two classes of regulatory genes under the control of the constitutive promoter ermE*p (cluster situated regulators (CSR) and Streptomyces antibiotic regulatory proteins (SARPs)). These plasmids were introduced into Streptomyces sp. TÜ17, Streptomyces sp. TÜ10 and Streptomyces sp. TÜ102. Introduction of the CSRs-plasmid into strain S. sp. TÜ17 activated the production of mayamycin A. By using the individual regulator genes, we proved that Aur1P, was responsible for the activation. In strain S. sp. TÜ102, the introduction of the SARP-plasmid triggered the production of a chartreusin-like compound. Insertion of the CSRs-plasmid into strain S. sp. TÜ10 resulted in activating the warkmycin-BGC. In both recombinants, activation of the BGCs was only possible through the simultaneous expression of aur1PR3 and griR in S. sp. TÜ102 and aur1P and pntR in of S. sp. TÜ10.
Application of S-1 Bifactor Model to Evaluate the Structural Validity of TMMS-24

(1) Background: Recent studies have shown that the internal structure of TMMS-24 can be conceptualized as a bifactor. However, these studies, based exclusively on the evaluation of the fit of the model, fail to show the existence of a general factor of strong emotional intelligence and have neglected the evaluation of the specific factors of attention, clarity and repair. The main goal of this work is to evaluate the degree of determination and reliability of the specific factors of TMMS-24 using a bifactor S-1 model. (2) Methods: We administered TMMS-24 to a sample of 384 students from middle and high schools (58.1% girls; mean age = 15.5; SD = 1.8). (3) Results: The specific TMMS-24 factors are better determined and present a higher internal consistency than the general factor. Furthermore, the bifactor S-1 model shows the existence of a hierarchical relationship between the attention factor and the clarity and repair factors. The S-1 bifactor model is the only one that was shown to be invariant as a function of the sex of the participants. (4) Conclusions: The S-1 bifactor model has proven to be a promising tool for capturing the structural complexity of TMMS-24. Its application indicates that it is not advisable to use the sum score of the items, since it would be contaminated by the attention factor. In addition, this score would not be invariant either, that is, comparisons by sex would be invalid.
Carbon/Silicone Nanocomposite-Enabled Soft Pressure Sensors with a Liquid-Filled Cell Structure Design for Low Pressure Measurement

In the fields of humanoid robots, soft robotics, and wearable electronics, the development of artificial skins entails pressure sensors that are low in modulus, high in sensitivity, and minimal in hysteresis. However, few sensors in the literature can meet all the three requirements, especially in the low pressure range (<10 kPa). This article presents a design for such pressure sensors. The bioinspired liquid-filled cell-type structural design endows the sensor with appropriate softness (Young’s modulus < 230 kPa) and high sensitivity (highest at 0.7 kPa−1) to compression forces below 0.65 N (6.8 kPa). The low-end detection limit is ~0.0012 N (13 Pa), only triple the mass of a bee. Minimal resistance hysteresis of the pressure sensor is 7.7%. The low hysteresis is attributed to the study on the carbon/silicone nanocomposite, which reveals the effect of heat treatment on its mechanical and electromechanical hysteresis. Pressure measurement range and sensitivity of the sensor can be tuned by changing the structure and strain gauge parameters. This concept of sensor design, when combined with microfluidics technology, is expected to enable soft, stretchable, and highly precise touch-sensitive artificial skins.
A Radiotracer for Molecular Imaging and Therapy of Gastrin-Releasing Peptide Receptor–Positive Prostate Cancer

Visual Abstract The gastrin-releasing peptide receptor (GRPR) is overexpressed in many solid malignancies, particularly in prostate and breast cancers, among others. We synthesized ProBOMB2, a novel bombesin derivative radiolabeled with 68Ga and 177Lu, and evaluated its ability to target GRPR in a preclinical model of human prostate cancer. Methods: ProBOMB2 was synthesized in solid phase using fluorenylmethoxycarbonyl chemistry. The chelator 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid was coupled to the N terminus and separated from the GRPR-targeting sequence by a cationic 4-amino-(1-carboxymethyl)-piperidine spacer. Binding affinity for both human and murine GRPR was determined using a cell-based competition assay, whereas a calcium efflux assay was used to measure the agonist and antagonist properties of the derivatives. ProBOMB2 was radiolabeled with 177Lu and 68Ga. SPECT and PET imaging and biodistribution studies were conducted using male immunocompromised mice bearing GRPR-positive PC-3 human prostate cancer xenografts. Results: Ga-ProBOMB2 and Lu-ProBOMB2 bound to PC-3 cells with an inhibition constant of 4.58 ± 0.67 and 7.29 ± 1.73 nM, respectively. 68Ga-ProBOMB2 and 177Lu-ProBOMB2 were radiolabeled with a radiochemical purity greater than 95%. Both radiotracers were excreted primarily via the renal pathway. PET images of PC-3 tumor xenografts were visualized with excellent contrast at 1 and 2 h after injection with 68Ga-ProBOMB2, and there was very low off-target organ accumulation. 177Lu-ProBOMB2 enabled clear visualization of PC-3 tumor xenografts by SPECT imaging at 1, 4, and 24 h after injection 177Lu-ProBOMB2 displayed higher tumor uptake than 68Ga-ProBOMB2 at 1 h after injection. 177Lu-ProBOMB2 tumor uptake at 1, 4, and 24 h after injection was 14.9 ± 3.1, 4.8 ± 2.1, and 1.7 ± 0.3 percentage injected dose per gram of tissue, respectively. Conclusion: 68Ga-ProBOMB2 and 177Lu-ProBOMB2 are promising radiotracers with limited pancreas uptake, good tumor uptake, and favorable pharmacokinetics for imaging and therapy of GRPR-expressing tumors.
Fluorimetric Analysis of Five Amino Acids in Chocolate: Development and Validation

Amino acids present ergogenic action, helping to increase, protect, and restore the muscular system of young athletes. Moreover, the encapsulation of five relevant amino acids in chocolate pellet form will appeal to them, facilitating their daily consumption. A reliable HPLC fluorimetric method was developed to detect and quantitatively determine L-Leucine, L-Isoleucine, L-Histidine, L-Valine, and β-Alanine in chocolate using aniline as an internal standard. Experimental design methodology was used to investigate and optimize the clean-up procedure of the samples. Therefore, three extraction techniques (solid-phase extraction (by two different SPE cartridges) and liquid–solid extraction (LSE)) were compared and evaluated. The LOQ values in chocolate varied from 24 to 118 ng/g (recovery 89.7–95.6%, %RSD < 2.5). Amino acids were pre-column derivatized with o-phthalaldehyde (OPA), while derivatization parameters were thoroughly investigated by experimental design methodology. The analysis was performed by HPLC-fluorescence (emission: λ = 455 nm, excitation: λ = 340 nm) method using a C18 column and a mixture of phosphate buffer (pH = 2.8; 20 mM)-methanol as a mobile phase in gradient elution. The method was validated (r2 > 0.999, %RSD < 2, LOD: 10 ng mL−1 for histidine and leucine, 2 ng mL−1 for alanine and valine, and 4 ng mL−1 for Isoleucine) according to the International Conference on Harmonization guidelines.