Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of a Novel Series of Anticancer and Antidiabetic: Spirothiazolidines Analogs

4-(4-Aminophenyl)-1-thia-4-azaspiro[4.5]decan-3-one 1 was prepared and allowed to react with nitrogen nucleophiles to give the corresponding hydrazones 2–4. Further, compound 1 underwent diazotization and afforded the parallel hydrazono derivative 5; moreover, compound 1 refluxed with active methylene derivatives yielded the corresponding aminospirothiazolo pyridine–carbonitrile derivative 6 and spirothiazolopyridinone–carbonitrile derivative 7. Condensation of spirothiazolidine 1 with 4-chlorobenzaldehyde gave the corresponding spiro arylidiene derivative 8, which was utilized as a component of Micheal addition to react with excess of nitrogen nucleophiles to yield novel ring frameworks 4-(3′-(4-chlorophenyl)–spiro [cyclohexane-1,5′-pyrazolo[3,4-d]thiazol]-6′(1′H)-yl)aniline (9) and 4-(3′-(4-chlorophenyl)-6′H- spiro[cyclohexane-1,5′-thiazolo[5,4-d]isoxazol]-6′-yl)aniline (10). Finally, when spirothiazolo pyridinone–carbonitrile derivative 7 sodium salt generated in situ was reacted with different alkyl halides, it produced the corresponding N-derivatives 12–16. Three compounds, 6, 14, and 16, showed high significantly anticancer activities compared with Doxorubicin® (positive control) against human breast carcinoma (MCF-7) and human liver carcinoma (HepG-2) cell lines. On the other hand, compounds 6 and 9 showed higher therapeutic indices for both of alpha-amylase inhibitor and alpha-glucosidase inhibitor than the other tested compounds compared with the antidiabetic Acarbose (positive control).
Neural Processing of Disorder-Related Stimuli in Patients with Anorexia Nervosa: A Narrative Review of Brain Imaging Studies

Abnormalities and alterations in brain function are commonly associated with the etiology and maintenance of anorexia nervosa (AN). Different symptom categories of AN have been correlated with distinct neurobiological patterns in previous studies. The aim of this literature review is to provide a narrative overview of the investigations into neural correlates of disorder-specific stimuli in patients with AN. Although findings vary across studies, a summary of neuroimaging results according to stimulus category allows us to account for methodological differences in experimental paradigms. Based on the available evidence, the following conclusions can be made: (a) the neural processing of visual food cues is characterized by increased top-down control, which enables restrictive eating, (b) increased emotional and reward processing during gustatory stimulation triggers disorder-specific thought patterns, (c) hunger ceases to motivate food foraging but instead reinforces disorder-related behaviors, (d) body image processing is related to increased emotional and hedonic reactions, (e) emotional stimuli provoke increased saliency associated with decreased top-down control and (f) neural hypersensitivity during interoceptive processing reinforces avoidance behavior. Taken together, studies that investigated symptom-specific neural processing have contributed to a better understanding of the underlying mechanisms of AN.
Activation of the STAT1 Pathway Accelerates Periodontitis in Nos3-/- Mice

Early studies on the etiology and pathogenesis of hypertension have shown that it has a considerable association with inflammation and the immune response as well as periodontitis. Clinical studies have also shown that hypertension can promote the periodontal tissue destruction caused by periodontitis. However, the underlying mechanisms remain unclear. This study aimed to explore the possible mechanisms of how hypertension aggravates periodontitis. Treatment with or without the signal transducer and activator of transcription 1 (STAT1) inhibitor fludarabine was performed in an endothelial nitric oxide synthase gene knockout-related (Nos3-/-) mouse model with the hypertension phenotype of periodontitis induced by bacteria. Micro–computed tomography, immunohistochemistry, Western blot, quantitative reverse transcription polymerase chain reaction, immunofluorescence, and ELISA were performed. We demonstrated that Nos3-/--related hypertension increases bone resorption and periodontal destruction in periodontitis lesion areas, which can be inhibited by the STAT1 inhibitor. Experimental data also showed that Nos3-/- significantly increased macrophage infiltration and proinflammatory cytokine expression in the periodontitis lesion area, which is dependent on the angiotensin II–induced STAT1 pathway. Inhibition of STAT1 in vivo can decrease the expression of proinflammatory cytokines and macrophage infiltration. Furthermore, data in this study showed that Nos3-/--related hypertension further downregulated the STAT3 anti-inflammatory function and its downstream chemokine expression in a STAT1-dependent manner. By applying RAW 264.7 and L929 cell lines and monocytes isolated from Nos3-/- mice, we confirmed that activation of the STAT1 pathway inhibits STAT3 and its downstream pathway and promotes inflammatory cytokine expression in vitro. Collectively, our current study demonstrated that STAT1 plays an indispensable role in the Nos3-/--related hypertension with aggravation of periodontitis, suggesting that STAT1 may be a key target for the treatment of periodontitis with hypertension.
Diachasmimorpha longicaudata Parasitism Response to Medfly Host Fruit and Fruit Infestation Age

The parasitoid Diachasmimorpha longicaudata (Ashmead) (Hymenoptera: Braconidae) is increasingly being used in integrated pest management (IPM) programs as a biological control agent in order to suppress tephritid fruit flies of economic importance. Innate and acquired behavioral responses—such as pest host fruit preference—of parasitoids can modulate their efficiency in the field and should be taken into consideration prior to parasitoid species’ selection for mass-rearing. We have assessed the influence of medfly-infested (two infestation ages, 1 and 4-d-old) and uninfested fruit species on host preference and efficiency of D. longicaudata by using a multistep assay including olfactory, laboratory and semi-field trials. We found that D. longicaudata was significantly more attracted to medfly-infested apples for both infestation ages, with the oldest being the most preferred. D. longicaudata exhibited a significant preference among the four fruits tested. The implications of these behavioral responses of D. longicaudata to medfly host fruits and infestation age are discussed in relationship to its use in IPM programs in the Mediterranean basin area.
Positional differences of intronic transposons in pAMT affect the pungency level in chili pepper through altered splicing efficiency.

Capsaicinoids are unique compounds that give chili pepper fruits their pungent taste. Capsaicinoid levels vary widely among pungent cultivars, ranging from low-pungency to extremely pungent. However, the molecular mechanisms underlying its quantitative variation have not been elucidated. Our previous study identified various loss-of-function alleles of the pAMT gene, which led to low-pungency. The mutations in these alleles are commonly defined by Tcc transposon insertion and its footprint. In this study, we identified two leaky pamt alleles (pamtL1 and pamtL2 ) with different levels of pAMT activity. Notably, both alleles had a Tcc transposon insertion in intron 3, but the locations of the insertions within the intron were different. Genetic analysis revealed that pamtL1 , pamtL2 and a loss-of-function pamt allele reduced capsaicinoid levels to about 50%, 10%, and less than 1%, respectively. pamtL1 and pamtL2 encoded functional pAMT proteins, but they exhibited lower transcript levels compared with the functional-type. RNA-seq analysis showed that intronic transposons disrupted splicing in intron 3, which resulted in simultaneous expression of functional pAMT mRNA and non-functional splice variants containing partial sequences of Tcc. The non-functional splice variants were more dominant in pamtL2 than that in pamtL1 . This suggested that the difference in position of the intronic transposons could alter splicing efficiency, which led to different pAMT activities and reduced capsaicinoid content to different levels. Our results provide a striking example where intronic transposons caused allelic variations, which contributed to quantitative differences in secondary metabolite contents. This article is protected by copyright. All rights reserved.
Ulipristal acetate on quality of life and sexual function of women with uterine fibromatosis

Abstract To evaluate quality of life and sexual function of childbearing-age women, affected by uterine fibromatosis undergoing medical treatment with ulipristal acetate. The data obtained by filling the questionnaires European Quality of Life Five-Dimension Scale and modified Female Sexual Function Index, were analyzed to assess UPA usefulness in improving QoL and sexual activity. A total of 139 patients affected by uterine fibromatosis undergoing conservative ulipristal acetate treatment were enrolled in this prospective observational cohort study. Seventy-one women (average age 46.5 years) answered the questionnaires: QoL and sexuality were evaluated before and after ulipristal acetate treatment. 59 patients (83.1%) had an improvement of QoL and general health state, with a reduction of VAS score after ulipristal acetate treatment. EQ-5D-5L showed a statistically significant improvement of usual act impairment, mobility, discomfort, anxiety/depression (p < .0005). There was no difference in personal care management after therapy. Modified FSFI showed a statistically significant improvement (p < .0001) of sexual satisfaction and sexual life. A not statistically significant improvement in dyspareunia was also highlighted. This study provides a clear picture about QoL impact on women and confirms the effectiveness of the ulipristal acetate in improving different aspects of daily and sexual life of patients undergoing medical treatment.
Transmission of Dental Fear from Parent to Adolescent in an Appalachian Sample in the USA.

BACKGROUND Dental fear/anxiety are associated with numerous negative outcomes. State dental fear is known to be transmitted from parents to their children in the dental setting, but it is not known how trait fear/anxiety might be shared between parents and offspring long-term, and especially for adolescents. AIM This study aimed to: (a) compare dental fear levels of adolescents and their parents; (b) predict adolescent dental fear based on demographic variables, fear of pain, and parental dental fear; and, (c) determine relative contributions of mothers' and fathers' dental fear to adolescent fear. DESIGN In this cross-sectional study, the Dental Fear Survey and Fear of Pain Questionnaire-9 were administered to 350 adolescents (age range 11-17) and 515 of their parents, with t-test and ANOVA used to calculate between-group differences; multiple linear regression was used to predict adolescent fear from parent fear. RESULTS Adolescents' dental fear was predicted by their own fear of pain and their parents' dental fear, but not their parents' fear of pain nor their own age or gender. When considered together, fathers' but not mothers' dental fear predicted adolescents' dental fear. CONCLUSIONS Parents' fears/anxieties about dentistry are associated with adolescents' dental fear in a manner suggestive of intergenerational transmission. This article is protected by copyright. All rights reserved.
Mortality from extrathymic malignancy after thymic tumour resections: incidences and risk factors.

OBJECTIVES To identify risk factors associated with extrathymic malignancy-related mortality after thymic epithelial tumour resection. METHODS The Japanese Association for Research on the Thymus database registered the records of 2835 patients collected from 32 Japanese institutions from 1991 to 2010. The cumulative incidence function of death due to extrathymic malignancies or recurrence was calculated, with other causes of death as competing risks. Relevant risk factors associated with extrathymic malignancy-related deaths in patients with thymoma were evaluated using the Fine and Gray model. RESULTS In total, 2701 patients were eligible for the analysis (thymoma, 2374; thymic carcinoma, 273; thymic neuroendocrine tumour, 54). The median follow-up period was 4.6 years. The cumulative incidence function of death due to extrathymic malignancies at 10 years was 2.2% (3.2% due to recurrence) in patients with thymoma, 1.6% (38.6% due to recurrence) in patients with thymic carcinoma and 0% (36.6% due to recurrence) in patients with thymic neuroendocrine tumour. In the multivariable analysis, age (every 10 years) at thymectomy [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.53-3.14; P < 0.001], male gender (HR 2.62, 95% CI 1.19-5.77; P = 0.017) and previous malignancies (HR 3.09, 95% CI 1.18-8.11; P = 0.022) were significant factors for death due to extrathymic malignancies after thymectomy. CONCLUSIONS Continued management and early detection of extrathymic malignancies may improve survival of patients with thymoma who are male, of advanced age, or have previous malignancies. Prospective studies are required to further investigate the management of extrathymic malignancies.
Electroactive Textile Actuators for Breathability Control and Thermal Regulation Devices

Smart fabrics offer the potential for a new generation of soft robotics and wearable technologies through the fusion of smart materials, textiles and electrical circuitries. Conductive and stretchable textiles have inherent compliance and low resistance that are suitable for driving artificial muscle actuators and are potentially safer electrode materials for soft actuation technologies. We demonstrate how soft electroactive actuating structures can be designed and fabricated from conducting textiles. We first quantitatively analyse a range of stretchable conductive textiles for dielectric elastomer actuators (DEAs). We found that conductive-knit textiles are more suitable for unidirectional DEA applications due to the largest difference (150%) in principle strain axes, whereas isotropic textiles are more suited to bidirectional DEA applications due to the smallest (11.1%) principle strain difference. Finally, we demonstrate controllable breathability through a planar e-textile DEA-driven skin and show thermal regulation in a wearable prototype that exploits soft actuation and kirigami.
Interactive Toxicity of Triclosan and Nano-TiO2 to Green Alga Eremosphaera viridis in Lake Erie: A New Perspective based on Fourier Transform Infrared Spectromicroscopy and Synchrotron-based X-ray Fluorescence Imaging.

This study explored the toxicity of triclosan in the presence of TiO2 P25 to the green alga Eremosphaera viridis in Lake Erie. Multiple physicochemical endpoints were conducted to perform a comprehensive analysis of the toxic effects of individual and combined pollutants. Fourier transform infrared spectromicroscopy and synchrotron-based X-ray fluorescence imaging were first documented to be applied to explore the distribution variation of macromolecules and microelements in single algal cells in interactive toxicity studies. The results were different based on different triclosan concentrations and measurement endpoints. Comparing with individual pollutants, the toxicity intensified in lipids, proteins and oxidative stress at 1000 and 4000 µg/L triclosan in the presence of P25. There were increases in dry weight, chlorophyll content, lipids, and catalase content when cells were exposed to P25 and 15.625 µg/L triclosan. The toxicity alleviated when P25 interacted with 62.5 and 250 μg/L triclosan compared with triclosan-only exposure. The reasons could be attributed to the combination of adsorption, biodegradation, and photocatalysis of triclosan by algae and P25, triclosan dispersion by increased biomass, triclosan adherency on algal exudates, and triclosan adsorption site reduction on algae surface owing to P25's taking-over. This work provides new insights into the interactive toxicity of nanoparticles and personal care products to freshwater photosynthetic organisms. The findings can help with risk evaluation for predicting outcomes of exposure to mixtures, and prioritize further studies on joint toxicity.
A practical composite risk score for the development of Haemolytic Uraemic Syndrome from Shiga toxin-producing Escherichia coli.

BACKGROUND Haemolytic Uraemic Syndrome (HUS) is a serious complication of Shiga toxin-producing Escherichia coli (STEC) infection and the key reason why intensive health protection against STEC is required. However, although many potential risk factors have been identified, accurate estimation of risk of HUS from STEC remains challenging. Therefore, we aimed to develop a practical composite score to promptly estimate the risk of developing HUS from STEC. METHODS This was a retrospective cohort study where data for all confirmed STEC infections in Ireland during 2013-15 were subjected to statistical analysis with respect to predicting HUS. Multivariable logistic regression was used to develop a composite risk score, segregating risk of HUS into 'very low risk' (0-0.4%), 'low risk' (0.5-0.9%), 'medium risk' (1.0-4.4%), 'high risk' (4.5-9.9%) and 'very high risk' (10.0% and over). RESULTS There were 1397 STEC notifications with complete information regarding HUS, of whom 5.1% developed HUS. Young age, vomiting, bloody diarrhoea, Shiga toxin 2, infection during April to November, and infection in Eastern and North-Eastern regions of Ireland, were all statistically significant independent predictors of HUS. Demonstration of a risk gradient provided internal validity to the risk score: 0.2% in the cohort with 'very low risk' (1/430), 1.1% with 'low risk' (2/182), 2.3% with 'medium risk' (8/345), 3.1% with 'high risk' (3/98) and 22.2% with 'very high risk' (43/194) scores, respectively, developed HUS. CONCLUSION We have developed a composite risk score which may be of practical value, once externally validated, in prompt estimation of risk of HUS from STEC infection.
A Promising Polymer Blend Electrolytes Based on Chitosan: Methyl Cellulose for EDLC Application with High Specific Capacitance and Energy Density

In the present work, promising proton conducting solid polymer blend electrolytes (SPBEs) composed of chitosan (CS) and methylcellulose (MC) were prepared for electrochemical double-layer capacitor (EDLC) application with a high specific capacitance and energy density. The change in intensity and the broad nature of the XRD pattern of doped samples compared to pure CS:MC system evidencedthe amorphous character of the electrolyte samples. The morphology of the samples in FESEM images supported the amorphous behavior of the solid electrolyte films. The results of impedance and Bode plotindicate that the bulk resistance decreasedwith increasing salt concentration. The highest DC conductivity was found to be 2.81 × 10−3 S/cm. The electrical equivalent circuit (EEC) model was conducted for selected samples to explain the complete picture of the electrical properties.The performance of EDLC cells was examined at room temperature by electrochemical techniques, such as impedance spectroscopy, cyclic voltammetry (CV) and constant current charge–discharge techniques. It was found that the studied samples exhibit a very good performance as electrolyte for EDLC applications. Ions were found to be the dominant charge carriers in the polymer electrolyte. The ion transference number (tion) was found to be 0.84 while 0.16 for electron transference number (tel). Through investigation of linear sweep voltammetry (LSV), the CS:MC:NH4SCN system was found to be electrochemically stable up to 1.8 V. The CV plot revealed no redox peak, indicating the occurrence of charge double-layer at the surface of activated carbon electrodes. Specific capacitance (Cspe) for the fabricated EDLC was calculated using CV plot and charge–discharge analyses. It was found to be 66.3 F g−1 and 69.9 F g−1 (at thefirst cycle), respectively. Equivalent series resistance (Resr) of the EDLC was also identified, ranging from 50.0 to 150.0 Ω. Finally, energy density (Ed) was stabilized to anaverage of 8.63 Wh kg−1 from the 10th cycle to the 100th cycle. The first cycle obtained power density (Pd) of 1666.6 W kg−1 and then itdropped to 747.0 W kg−1 at the 50th cycle and continued to drop to 555.5 W kg−1 as the EDLC completed 100 cycles.
No transcriptional evidence for active Nav channels in two classes of cancer cell

ABSTRACT Voltage-gated sodium channel (Nav) expression in non-excitable cells has raised questions regarding their non-canonical roles. Interestingly, a growing body of evidence also points towards the prevalence of aberrant Nav expression in malignant tumors, potentially opening a new therapeutic window. In this study, the transcriptional consequences of channel inhibition were investigated in non-small cell lung carcinoma H460 and neuroblastoma SH-SYSY cell lines, that both express Nav1.7. Channel activity was blocked by the application of both selective, ProTx-II, and non-selective, tetrodotoxin, inhibitors. Global gene expression profiling did not point to any statistically significant inhibition-associated perturbation of the transcriptome. A small subset of genes that showed relatively consistent changes across multiple treatments were further assayed in the context of a multiplex bead expression array which failed to recapitulate the changes seen in the global array. We conclude that there is no robust transcriptional signature associated with the inhibition of two sodium channel expressing cancer cell lines and consequently sodium channel inhibition will not lend itself to therapeutic approaches such as transcription-based drug repurposing.
Transcriptional control and transcriptomic analysis of lipid metabolism in skin barrier formation and atopic dermatitis (AD)

ABSTRACT Introduction: Atopic dermatitis (AD) is a multifactorial ailment associated with barrier breach and intense systemic inflammation. Several studies over the years have shown the complex interplay of a large number of factors in governing the progression and outcome of AD. In addition to the diverse types of AD resulting due to variation in the intrinsic mechanisms giving rise to AD such as single nucleotide polymorphisms (SNPs), epigenetic alterations or transcriptional changes, extrinsic factors such as age, ancestry, ethnicity, immunological background of the subject, the interactions of the subject with environmental stimuli and existing microbiome in the periphery surrounding the subject account for further heterogeneity in the clinical manifestations of the disease. Areas covered: Here we have selectively discussed transcriptional regulation of genes associated with skin lipid metabolism in the context of AD. Transcriptional control and transcriptomic changes are just one face of this multifaceted disease known to affect humans and a detailed study concerning those will enable us to develop targeted therapies to deal with the disease. Expert opinion: Large-scale integration of different omics approaches (genomics, epigenomics, transcriptomics, lipidomics, proteomics, metabolomics, effect of exposome) will help identify the potential candidate gene(s) associated with the development of various endotypes of AD.