The Potential of Molecular Docking for Predictive Toxicology.

Molecular modeling techniques are widely used in medicinal chemistry for the study of biological targets, the rational design of new drugs, or the investigation of their mechanism of action.They are also applied in toxicology to identify chemical potential harmful effects.Molecular docking is a computational technique to predict the ligand binding mode and evaluate the interaction energy with a biological target.This chapter describes a computational workflow to predict possible endocrine disruptors on peroxisome proliferator-activated receptor alpha (PPARα), a nuclear receptor involved in glucose and lipid metabolism. The analyzed compounds are food contact chemicals, natural or synthetic substances intentionally added to food or released from the package or during production or technological processes.

Monitoring Calcium-Sensing Receptor (CaSR)-Induced Intracellular Calcium Flux Using an Indo-1 Flow Cytometry Assay.

The calcium-sensing receptor (CaSR) has a critical role in maintaining serum calcium concentrations within the normal physiological range, and mutations in the receptor, or components of its signaling and trafficking pathway, cause disorders of calcium homeostasis. Inactivating mutations cause neonatal severe hyperparathyroidism or familial hypocalciuric hypercalcemia (FHH), while gain-of-function mutations cause autosomal dominant hypocalcemia (ADH). Characterizing the functional impact of mutations of the CaSR, and components of the CaSR-signaling pathway, is clinically important to enable correct diagnoses of FHH and ADH, optimize management, and prevent inappropriate parathyroidectomy or vitamin D supplementation. CaSR signals predominantly by activating the G-alpha subunit-11 to mobilize calcium release from intracellular stores. Thus, measurement of CaSR-induced intracellular calcium (Ca2+i) signaling is the gold standard method to investigate the pathogenicity of CaSR genetic variants. This protocol describes a method to assess CaSR-induced Ca2+I signaling using the Indo-1 calcium indicator dye and flow cytometry. This method has been used to assess multiple genetic variants in CaSR and components of its signaling and trafficking pathway in HEK293 cells.

Interleukin-11Rα2 in the hypothalamic arcuate nucleus affects depression-related behaviors and the AKT-BDNF pathway.

Depression is a widespread emotional disorder with complex pathogenesis. An essential function of the hypothalamus is to regulate emotional disorders. However, further investigation is required to identify the pathogenic genes and molecular mechanisms that contribute to the onset of depression within the hypothalamus. Through RNA-sequencing analysis, this study identified the upregulated expression of interleukin-11 receptor alpha 2 (IL-11Rα2) in the hypothalamus of mice with chronic unpredictable stress (CUS)-induced depression. This substantial increase in IL-11Rα2, not IL-11Rα1 expression levels in the hypothalamus under the influence of CUS was found to be associated with depression-related behaviors. We further showed that IL-11Rα2 is expressed in the arcuate nucleus (ARC) proopiomelanocortin (POMC) neurons of the hypothalamus. Male and female mice exhibited behaviors association with depression, when IL-11Rα2 or its ligand IL-11 was overexpressed in the ARC POMC neurons through the action of an adeno-associated virus. In addition, reductions in the expression levels of proteins involved in the protein kinase B signaling pathways and brain-derived neurotrophic factor were observed upon overexpression of IL-11Rα2 in the hypothalamic ARC. This study emphasizes the importance of IL-11Rα2 in the hypothalamus ARC in the development of depression, and presents it as a potential novel target for depression treatment.

Enhancing anticorrosion performance of metals by incorporating cellulose nanofibrils/α-ZrP composite as nanofiller into water-based coating.

The anticorrosion of metals has gain considerable interest in view of economic and environmental issues. Coating protection is one of the most effective and cost-effective methods for anticorrosion of metals. However, the traditional coatings often suffer from many issues such as poor performance or high cost. For the first time, a strategy was proposed by constructing cellulose nanofibrils (CNF)/alpha­zirconium phosphate (α-ZrP) composite as nanofiller and incorporating into water-based coatings for anticorrosion of metals. The successful coordination of α-ZrP nanosheet and CNF were characterized. The effects of the resultant composite on anticorrosion performance were investigated. The results showed that, the as-prepared coating exhibited superior anticorrosion performance to commercial coatings. The impedance of the test sample coated with the as-prepared coating reached up to 4.38 × 105 Ω when it was immersed in 3.5 % NaCl solution with few corrosions fragmentation on metal surface, exhibiting a favorable long-term anticorrosion performance. Meanwhile, the anticorrosion mechanism was proposed. It is expected that this strategy would provide novel solutions for developing highly efficient water-based anticorrosive coatings of metals.

Anterior lamellar corneoscleral keratoplasty for the management of corneal thinning following treatment with mitomycin-C and interferon to treat highly suspected ocular surface squamous neoplasia: a case report

ABSTRACT A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.

Investigation in the cannabigerol derivative VCE-003.2 as a disease-modifying agent in a mouse model of experimental synucleinopathy.

BACKGROUND: The cannabigerol derivative VCE-003.2, which has activity at the peroxisome proliferator-activated receptor-γ has afforded neuroprotection in experimental models of Parkinson's disease (PD) based on mitochondrial dysfunction (6-hydroxydopamine-lesioned mice) and neuroinflammation (LPS-lesioned mice). Now, we aim to explore VCE-003.2 neuroprotective properties in a PD model that also involves protein dysregulation, other key event in PD pathogenesis. METHODS: To this end, an adeno-associated viral vector serotype 9 coding for a mutated form of the α-synuclein gene (AAV9-SynA53T) was unilaterally delivered in the substantia nigra pars compacta (SNpc) of mice. This model leads to motor impairment and progressive loss of tyrosine hydroxylase-labelled neurons in the SNpc. RESULTS: Oral administration of VCE-003.2 at 20 mg/kg for 14 days improved the performance of mice injected with AAV9-SynA53T in various motor tests, correlating with the preservation of tyrosine hydroxylase-labelled neurons in the SNpc. VCE-003.2 also reduced reactive microgliosis and astrogliosis in the SNpc. Furthermore, we conducted a transcriptomic analysis in the striatum of mice injected with AAV9-SynA53T and treated with either VCE-003.2 or vehicle, as well as control animals. This analysis aimed to identify gene families specifically altered by the pathology and/or VCE-003.2 treatment. Our data revealed pathology-induced changes in genes related to mitochondrial function, lysosomal cell pathways, immune responses, and lipid metabolism. In contrast, VCE-003.2 treatment predominantly affected the immune response through interferon signaling. CONCLUSION: Our study broadens the neuroprotective potential of VCE-003.2, previously described against mitochondrial dysfunction, oxidative stress, glial reactivity and neuroinflammation in PD. We now demonstrate its efficacy against another key pathogenic event in PD as α-synuclein dysregulation. Furthermore, our investigation sheds light on the molecular mechanisms underlying VCE-003.2 revealing its role in regulating interferon signaling. These findings, together with a favorable ADMET profile, enhance the preclinical interest of VCE-003.2 towards its future clinical development in PD.

Clinical trials of intratesticular administration of nanostructured lipid carriers encapsulated alpha-mangostin: Safety and efficacy on feline reproductive health.

Surgical castration is a primary method for controlling male fertility, but it is impractical for large-scale population control of stray animals. Developing nanoparticle-mediated sterilants that induce cell apoptosis rather than necrosis is a complex and promising area of research. This study aimed to investigate the impact of intratesticular administration of alpha-mangostin encapsulated in nanostructured lipid carriers (AM-NLC) on testicular changes and any associated adverse effects over a 168-day observation period. Thirty-two healthy mature tomcats were enrolled. None of the cats treated with either AM-NLC (n = 28) or blank NLC (n = 4) exhibited noticeable complications related to pain or stress throughout the study, as assessed by clinical examination, blood profiles, and serum amyloid A levels. Histopathological analysis of AM-NLC treated cats revealed seminiferous epithelium degeneration, leading to defective tubules. Key findings included germ cell depletion, disorganized spermatogenic cells without spermatids in certain areas, apoptotic bodies, and intracytoplasmic vacuolization. The intertubular compartment showed no signs of inflammation, hyalinization, fibrosis, or necrosis. Despite widespread degeneration, some normal tubules were present in focal areas. The severity score of seminiferous tubule degeneration significantly increased from day 56 onwards (P < 0.05), suggesting a gradual and progressive compromise of the seminiferous epithelium. In contrast, testes from the blank-NLC group exhibited normal spermatogenesis. Overall, there were no significant changes in the volume of dissected testes, serum testosterone levels, or apoptotic index in AM-NLC-treated cats (P > 0.05). In conclusion, this study represents the first in vivo investigation of apoptotic-inducing agents as a novel nanomedicine-based antifertility compound for non-surgical castration in male animals. While the AM-NLC formulation proved safe for intratesticular administration, it failed to induce infertility in cats, as epididymal spermatozoa persisted throughout the study. Further research into alternative apoptosis-inducing nanomedicine sterilants remains both essential and challenging.

Neurophysiological Dynamics of Metacontrol States: EEG Insights into Conflict Regulation.

Understanding the neural mechanisms underlying metacontrol and conflict regulation is crucial for insights into cognitive flexibility and persistence. This study employed electroencephalography (EEG), EEG-beamforming and directed connectivity analyses to explore how varying metacontrol states influence conflict regulation at a neurophysiological level. Metacontrol states were manipulated by altering the frequency of congruent and incongruent trials across experimental blocks in a modified flanker task, and both behavioral and electrophysiological measures were analyzed. Behavioral data confirmed the experimental manipulation's efficacy, showing an increase in persistence bias and a reduction in flexibility bias during increased conflict regulation. Electrophysiologically, theta band activity paralleled the behavioral data, suggesting that theta oscillations reflect the mismatch between expected metacontrol bias and actual task demands. Alpha and beta band dynamics differed across experimental blocks, though these changes did not directly mirror behavioral effects. Post-response alpha and beta activity were more pronounced in persistence-biased states, indicating a neural reset mechanism preparing for future cognitive demands. By using a novel artificial neural networks method, directed connectivity analyses revealed enhanced inter-regional communication during persistence states, suggesting stronger top-down control and sensorimotor integration. Overall, theta band activity was closely tied to metacontrol processes, while alpha and beta bands played a role in resetting the neural system for upcoming tasks. These findings provide a deeper understanding of the neural substrates involved in metacontrol and conflict monitoring, emphasizing the distinct roles of different frequency bands in these cognitive processes.

Enhanced photocurrents for photoelectrochemical immunoassay of alpha-fetoprotein with Pt-functionalized Bi2O2S nanoflowers.

BACKGROUND: Designing heterojunctions with efficient electron-hole separation holds great promise for improving photoelectric response. RESULTS: Herein, we reported a multifunctional Pt co-catalyst-modified Bi2O2S nanoflowers (BOS NFs) photocatalytic component for achieving an efficient photoelectric chemistry (PEC) immunosensor for alpha-fetoprotein (AFP). Briefly, the Pt co-catalyst improved the intrinsic band gap structure of BOS on the one hand, and on the other hand, it was able to achieve a rapid decomposition of hydrogen peroxide to hydroxyl radicals, which led to the improvement of electrochemical half-responses during the amplification of target immunosignals. In addition, Pt-functionalized BOS NFs (BOS-Pt) exhibited peroxidase-like enzymatic reaction activity and related properties. By enzyme-linked immunosorbent assay, a sandwich immuno-model in the presence of AFP catalyzed the production of hydrogen peroxide from the substrate glucose and the conversion of a sizable photoelectrochemical signal catalyzed by BOS-Pt. Following condition optimization, it was determined that the developed sensor exhibited a specific response to AFP over a wide linear range of 0.05-50 ng mL-1. SIGNIFICANCE: This work provides a new strategy for developing efficient immunosensors from the perspective of modulating photoelectrochemical half-reactions.

TREM2 signaling in Parkinson's disease: Regulation of microglial function and α-synuclein pathology.

BACKGROUND: Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons, abnormal accumulation of α-synuclein (α-syn), and microglial activation. Triggering receptor expressed on myeloid cells 2 (TREM2) regulates multiple functions of microglia in the brain, and several studies have shown that TREM2 variant R47H is a risk factor for PD. However, the regulation of microglia by TREM2 in PD remains poorly understood. METHODS: We constructed PD cell and animal models using α-syn preformed fibrils. siRNA knockdown and lentiviral overexpression were used to perturb TREM2 levels in cells, and TREM2 knockout mice and lentiviral overexpression was used in animal models to investigate the effects of TREM2 on microglial function, α-syn-related pathology, and dopaminergic neuron degeneration. RESULTS: Microglia phagocytosed α-syn preformed fibrils in a concentration- and time-dependent manner, with some capacity to degrade α-syn aggregates. TREM2 expression increased in PD. In the context of PD, TREM2 knockout mice exhibited worsened pathological α-syn spread, decreased microglial reactivity, and increased loss of TH-positive neurons in the substantia nigra compared to wild-type mice. TREM2 overexpression enhanced reactive microglial aggregation towards the pathological site. Cellular experiments revealed that reduced TREM2 impaired microglial phagocytosis and proliferation, but enhanced autophagy via the PI3K/AKT/mTOR pathway. CONCLUSION: TREM2 signaling in PD maintains microglial phagocytosis, proliferation, and reactivity, stabilizing autophagy and proliferation via the PI3K/AKT/mTOR pathway. Regulating TREM2 levels may be beneficial in PD treatment.

Glucocorticoid receptor and specificity protein 1 (Sp1) or Sp3 transactivate HSV-1 ICP0 promoter sequences but a GC-rich binding antibiotic, Mithramycin A, impairs reactivation from latency.

Glucocorticoid receptor (GR) activation enhances Human alpha-herpes virus 1 (HSV-1) replication and explant-induced reactivation from latency. Furthermore, GR and Krüppel-like factor 15 (KLF15) cooperatively transactivate cis-regulatory modules (CRMs) that drive expression of infected cell protein 0 (ICP0), ICP4, and ICP27. KLF and specificity protein (Sp) family members bind GC-rich or C-rich sequences and belong to the same super-family of transcription factors. Based on these observations, we hypothesized CRMs spanning the ICP0 promoter are transactivated by GR and Sp1 or Sp3. CRM-A (-800 to -635), CRM-B (-485 to -635), and CRM-D (-232 to -24), but not CRM-C, were significantly transactivated by GR, DEX, and Sp1 or Sp3 in mouse neuroblastoma cells (Neuro-2A). Mutagenesis of Sp1/Sp3 binding sites were important for transactivation of CRM-A and CRM-B. Chromatin immunoprecipitation studies revealed significantly higher levels of GR occupied ICP0 promoter sequences when Sp1 or Sp3 was over-expressed suggesting these transcriptions factors recruit GR to ICP0 CRM sequences. Mithramycin A, an antibiotic that preferentially binds GC-rich DNA and impairs Sp1/Sp3 dependent transactivation also reduced virus shedding reactivation from latency in mice latently infected with HSV-1. These studies indicate GR and certain stress-induced cellular transcription factors preferentially bind GC rich DNA, which stimulates HSV-1 gene expression and reactivation from latency in trigeminal ganglia of latently infected mice.

The European reference network for metabolic diseases (MetabERN) clinical pathway recommendations for Pompe disease (acid maltase deficiency, glycogen storage disease type II).

Clinical pathway recommendations (CPR) are based on existing guidelines and deliver a short overview on how to deal with a specific diagnosis, resulting therapy and follow-up. In this paper we propose a methodology for developing CPRs for Pompe disease, a metabolic myopathy caused by deficiency of lysosomal acid alpha-glucosidase. The CPR document was developed within the activities of the MetabERN, a non-profit European Reference Network for Metabolic Diseases established by the European Union. A working group was selected among members of the MetabERN lysosomal storage disease subnetwork, with specific expertise in the care of Pompe disease, and patient support group representatives. The working strategy was based on a systematic literature search to develop a database, followed by quality assessment of the studies selected from the literature, and by the development of the CPR document according to a matrix provided by MetabERN. Quality assessment of the literature and collection of citations was conducted according to the AGREE II criteria and Grading of Recommendations, Assessment, Development and Evaluation methodology. General aspects were addressed in the document, including pathophysiology, genetics, frequency, classification, manifestations and clinical approach, laboratory diagnosis and multidisciplinary evaluation, therapy and supportive measures, follow-up, monitoring, and pregnancy. The CPR document that was developed was intended to be a concise and easy-to-use tool for standardization of care for patients among the healthcare providers that are members of the network or are involved in the care for Pompe disease patients.

The Association and diagnostic value between Maternal Serum Placental Markers and Placenta Previa.

Objective: This study aims to evaluate the correlation and diagnostic value of maternal serum placental markers: pregnancy-associated plasma protein-A (PAPP-A), free beta human chorionic gonadotropin (free ß-hCG), and alpha fetoprotein (AFP) in relation to placenta previa. Methods: A retrospective case-control study was conducted to gather data on 137 pregnant women who were hospitalized for delivery at Hangzhou Women's Hospital. These women participated in the late stage of early and mid-term maternal serum prenatal screening between January 2018 and December 2020. Of the 137 women, 45 were diagnosed with placenta previa, while 92 were selected at random as the control group, in a ratio of 1: 2. Independent samples t-test or Mann-Whitney U test were utilized to compare the quantitative data of the two groups, and the Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic value of maternal serum placental marker levels for placenta previa. Results: The levels of first trimester and second trimester free beta subunit of human chorionic gonadotropin (FT-Free ß-hCG; ST-Free ß-hCG) in the placenta previa group were higher than those in the normal group [1.38 (0.55-6.03) MoM vs.1.08 (0.32-4.00) MoM, 1.38 (0.39-4.10) MoM vs.1.01 (0.29-4.12) MoM], and the differences between the groups were statistically significant (Z = 2.830, Z = 2.846, both P < 0.05). The AFP level was higher than the normal group [1.13 (0.65-2.15) MoM vs. 0.94 (0.51-2.02) MoM], and the difference was statistically significant (Z = 2.551, P < 0.05). There was no significant difference in PAPP-A between the placenta previa group and the normal group (Z = 1.396, P > 0.05). The ROC curve analysis results showed that the AUCs of FT-Free ß-hCG and ST-Free ß-hCG for placenta previa were 0.649 (95 % CI: 0.551-0.747, P = 0.005), 0.634 (95 % CI: 0.539-0.730, P = 0.011), and 0.650 (95 % CI: 0.554-0.746, P = 0.004). Using PPV, NPV, FPR, FNR, +LR, and -LR as evaluation indicators for the 5 models, the results showed that FT-Free ß-hCG was the best performer in terms of PPV, FPR, and +LR, with values of 0.725, 0.600, and 2.632, respectively. The three-indicator combined detection model (AFP + ST-Free ß-hCG + FT-Free ß-hCG) had the best performance in terms of NPV and -LR, with values of 0.770 and 0.298, respectively. Conclusion: The elevated maternal serum levels of Free ß-hCG and AFP may be associated with placenta previa. The combined detection of maternal serum markers in the early and mid-trimesters has better diagnostic value for predicting placenta previa than individual detection.

Early Outcomes of the Surgical Treatment of Sacrococcygeal Tumors in a Tertiary Level Government Hospital.

Objectives: Sacrococcygeal teratomas (SCT) are the most common extragonadal tumors of early childhood. Their clinical characteristics and outcomes of patients with sacrococcygeal tumors who underwent excision in the Philippines has never been described, while numerous retrospective studies have been conducted in other countries. Methods: This was a retrospective, descriptive study over a four-year period (December 2014 to November 2018). The study described the patients' demographic data, manner of delivery, clinical presentation, prenatal diagnosis of tumor, Altman classification, and alpha fetoprotein levels. These information were obtained from the medical records of the patients. Additional data from the operative technique include the surgical approach, size of the mass, and gross involvement of adjacent structures and the final histopathologic results. Outcomes include the 30-day mortality and morbidity, and tumor recurrence. Results: A total of 29 patients were included in the study with 22 females (75.86%) and seven males (24.14%). Twenty-five out of the 29 (86.21%) had a sacral or gluteal mass at birth while other presenting factors include a palpable abdominal mass (1), constipation (1), difficulty in urination (1), and an elevated AFP in one postoperative patient. Even if 27 out of the 29 patients underwent a maternal ultrasound, only three patients (10.34%) had a correct ultrasound interpretation of sacrococcygeal teratoma. Age at presentation was problematic, with 12 presenting at greater than one year of age while 10 were brought for consultation at greater than one month old. Only seven presented at the neonatal period. CT scan was the most common imaging tool utilized (37.93%), followed by ultrasound (27.59%). AFP was elevated in ten patients (34.48%). Six of the patients with elevated AFP had mature teratoma, two had yolk sac tumor, one had fibroepithelial polyp, and one was post chemotherapy but had mature teratoma based on the final histopathology report. Fifteen out of the 29 patients had Altman type I tumors (51.72%), seven (24.14%) had type II tumors, six (20.69%) had type III tumors, and only one patient had type IV tumor. Sacral approach in the excision of the sacrococcygeal tumor was performed in 25 patients (86.21%). There was no reported perioperative mortality for patients who underwent surgery for SCT during the study period. Twelve out of the 29 had postop morbidities, three with surgical site infection and three with rectal or vaginal perforation. Five patients had tumor recurrence occurring from two months to three years postoperatively. Conclusion: Early detection of sacrococcygeal teratomas even in the prenatal period is the norm in certain areas of the world, but in our country, prenatal detection is still a challenge. Even if the majority of the patients presented with a gluteal mass at birth, less than a third were brought to our tertiary government hospital in neonatal life. The sacral approach for SCT excision was employed for the great majority of our patients, but due to the advanced age at diagnosis and locally advanced disease, morbidities occurred in about a third of the patients. Therefore, early detection prenatally and early referral to a pediatric surgical center should be achievable goals for physicians dealing with these patients.

Characteristics and outcomes of ICU-admitted COVID-19 patients in the Omicron and Alpha-dominated periods.

BACKGROUND: Comparing the outcomes of intensive care unit (ICU) admitted COVID-19 patients during the Alpha and Omicron-dominated periods. METHODS: Patients with critical COVID-19 disease, requiring ICU admission from May to September 2021 and February to August 2022, were enrolled from a single medical center in Northern Taiwan. Clinical demographics, comorbidities, disease severity, and management strategies were recorded. The 28-day mortality from the two periods were compared both in the original and propensity score (PS)-matched cohort. RESULTS: Of 231 patients, 72 (31.2%) were from the Alpha period and 159 (68.8%) from the Omicron period. Patients in the Omicron period were older, had a lower body mass index, more comorbidities, higher disease severities, and increased 28-day mortality (26.4% vs. 13.9%, p = 0.035). In multivariable analysis, the Omicron-dominated period was not identified as an independent factor associated with increased 28-day mortality. COVID-19 patients in Alpha- and Omicron-dominated periods had comparable 28-day mortality in PS-matched cohort (12.1% vs. 18.2%, p = 0.733). Independent factors associated with 28-day mortality were a lower PF ratio (PF ratio <100, adjusted odds ratio [aOR] 2.68, 95% confidence interval, CI 1.21-5.94), septic shock ([aOR] 2.39, 95% CI 1.12-5.09) and absence of remdesivir ([aOR] 0.36, 95% CI 0.16-0.83). CONCLUSION: While patients in the Omicron period exhibited greater severity, the variant was not independently linked to higher 28-day mortality in ICU-admitted patients.

Exercise intensity measurement using fractal analysis of heart rate variability: Reliability, agreement and influence of sex and cardiorespiratory fitness.

The study aimed to establish the test-retest reliability of detrended fluctuation analysis of heart rate variability (DFA-α1) based exercise intensity thresholds, assess its agreement with ventilatory- and lactate-derived thresholds and the moderating effect of sex and cardiorespiratory fitness (CRF) on the agreement. Intensity thresholds for thirty-seven participants (17 females) based on blood lactate (LT1/LT2), gas-exchange (VT1/VT2) and DFA-α1 (αTh1/αTh2) were assessed. Heart rate (HR) at αTh1 and αTh2 showed good test-retest reliability (coefficient of variation [CV] < 6%), and moderate to high agreement with LTs (r = 0.40 - 0.57) and VTs (r = 0.61 - 0.66) respectively. Mixed effects models indicated bias magnitude depended on CRF, with DFA-α1 overestimating thresholds versus VTs for lower fitness levels (speed at VT1 <8.5 km⋅hr-1), while underestimating for higher fitness levels (speed at VT2 >15 km⋅hr-1; VO2max >55 mL·kg-1·min-1). Controlling for CRF, sex significantly affected bias magnitude only at first threshold, with males having higher mean bias (+2.41 bpm) than females (-1.26 bpm). DFA-α1 thresholds are practical and reliable intensity measures, however it is unclear if they accurately represent LTs/VTs from the observed limits of agreement and unexplained variance. To optimise DFA-α1 threshold estimation across different populations, bias should be corrected based on sex and CRF.

Purification and characterization of α-galactosidases from Penicillium griseoroseum for efficient soymilk hydrolysis.

Soybean utilization is limited by the presence of raffinose oligosaccharides (RFO), which are not digested by humans and cause gastrointestinal discomfort. This study explores the potential of α-galactosidases from Penicillium griseoroseum for RFO hydrolysis in soymilk. Two distinct α-galactosidase enzymes, designated α-Gal1 and α-Gal2, were purified using a combination of ion-exchange chromatography and native polyacrylamide gel electrophoresis. Both enzymes exhibited characteristics of multimeric proteins and displayed similar biochemical properties. Optimal activity was observed at a pH range of 4.5-5.0 and a temperature range of 40-45 °C. Notably, α-Gal1 demonstrated high thermostability with a half-life of 16 h at 40 °C. The α-galactosidases displayed different substrate affinitiesfor the substrates ρ-NP-αGal, o-NP-αGal, rD-raffinose, d-stachyose, and mD-melibiose. The Michaelis-Menten constant (Km) values for α-Gal1 were 1.06, 1.31, 28.74, 19.88, and 4.77 mmol/L, respectively, while those for α-Gal2 were 0.8, 1.26, 30.46, 21.74 and 5.01 mmol/L, respectively. Both α-Gal1 and α-Gal2 were strongly inhibited by metal ions (Ag⁺, Cu2⁺, Fe2⁺, and Hg2⁺) and moderately inhibited by d-melibiose. Importantly, both enzymes efficiently hydrolyzed RFOs, achieving complete d-stachyose elimination from soymilk after a 6-h incubation. These findings propose the promising application of these α-galactosidases in industrial soymilk production, potentially enhancing its nutritional value and alleviating gastrointestinal issues in consumers.

Enhanced Delta-gamma Phase Amplitude Coupling during Phasic REM Sleep in isolated REM Sleep Behavior Disorder.

STUDY OBJECTIVES: This study aims to analyze phase-amplitude coupling (PAC) patterns during rapid eye movement (REM) sleep in patients with isolated REM sleep behavior disorder (iRBD), compared with demography-matched healthy control (HC) participants. METHODS: At baseline, electroencephalogram data from 13 iRBD patients and 10 HCs during REM sleep were analyzed. During follow-up, 4 patients (converters) later converted to alpha-synucleinopathies. Phasic and tonic REM states were determined by eye movement in 3-second epochs. PAC was compared between the groups, and correlations with clinical indicators were investigated. Additionally, the contribution of each electrode to PAC components was assessed. RESULTS: Patients with iRBD exhibited increased delta (1-3 Hz)-gamma (30-50 Hz) PAC only during the phasic REM state, but not during the tonic state, compared to the HCs (p < 0.05). Elevated PAC in patients negatively correlated with the REM atonia index (p = 0.011) and olfactory function (p = 0.038). Increase PACs were predominent in the fronto-temporo-occipital regions (corrected p < 0.05). Furthermore, patients showed reduced gamma-amplitude contributions of the parietal region (corrected p < 0.05). This reduction exhibited a progressively decreasing trend from HC to non-converters, and further to converters (p for trend = 0.044). CONCLUSIONS: Our findings suggest PAC patterns during REM sleep could provide pathophysiological insights for iRBD. The widespread increase of PAC and reduced gamma-amplitude contribution in the parietal region suggest PAC during phasic REM sleep as potential biomarkers for disease progression in iRBD.

Frontal alpha and parietal theta asymmetries associated with color-induced emotions.

This study investigates the relationship between color perception-hue, brightness, and saturation-and its emotional response-valence, arousal, and pleasure-, through subjective evaluations, as well as their association with frontal and parietal asymmetric activity patterns through electroencephalographic (EEG) recording. Using the 37 colors from the Berkeley Color Project, along with positive and negative control images, we examined the perceptual and emotional dimensions of color in 32 Mexican participants (19 women; M = 21.4 years, SD = 3.3). Subjective evaluations revealed a strong positive correlation between valence and brightness, and between arousal and saturation. Brighter, arousing, and pleasant colors were associated with greater cortical activation (decreased alpha power) in the left dorsolateral prefrontal region-i.e., F3 electrode-, indicating positive emotional processing according to the frontal alpha asymmetry model. Additionally, increased theta power in the right lateral parietal region-i.e., P4 electrode-correlated with higher positive emotional and pleasurable responses. Our findings are in line with studies suggesting universal consistencies in how perceptual color dimensions relate to emotional responses. Moreover, significant correlations between subjective emotional responses and asymmetrical EEG activity models are highlighted, providing insights into the neural mechanisms of color-induced emotion perception, as no other study has done before to our knowledge. Further research should explore these associations using higher spatial resolution imaging techniques and larger electrode arrays to define precise cortical and subcortical regions involved. These results contribute to understanding color perception's impact on emotions, with potential applications in mental health treatments, such as chromotherapy for mood disorders.

An ingenious electrochemical system based on naphthalenediimide derivatives for ultrasensitive immunosensing of alpha-fetoprotein.

It is crucial to develop highly efficient electrochemistry systems for sensitive detection of tumour markers. In this work, naphthalenediimide derivatives with electrochemical application potential were successfully synthesized and characterized. Electrochemistry and calculation of density functional theory (DFT) showed that 2,7-bis(4-(dimethylamino)phenyl)benzo[lmn] [3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone (NDI-1) was an ideal candidate for electrochemical probe construction. Subsequently, based on the cyclic catalytic effect between NDI-1 and K2S2O8, a satisfying composite of GO/NDI-1/AuNPs was prepared and used to construct electrochemical probe for the design of ingenious sandwiched electrochemical immunosensor. Taking alpha-fetoprotein (AFP) as the model target biomarker, the designed immunosensor showed good detection performance for AFP, which exhibited wide range of linear response (10 fg/mL - 10 ng/mL), low detection limit (3.3 fg/mL). Moreover, the proposed immunosensor has been successfully applied to AFP detection in human serum, which provides the possibility for clinical applications. The designed electrochemical system provides a new electrochemical probe for the construction of immunosensors and may be extended to the electroanalysis of other biomolecules with recognition units.