This study aimed to identify candidate genes as potential biomarkers in nasopharyngeal carcinoma (NPC) by bioinformatical analysis.

Selective androgen receptor modulators (SARMs) have been proposed as therapeutics for women suffering from breast cancer, muscle wasting or urinary incontinence. The androgen receptor (AR) is expressed in the uterus but the impact of SARMs on the function of this organ is unknown. We used a mouse model to compare the impact of SARMs (GTx-007/Andarine®, GTx-024/Enobosarm®), Danazol (a synthetic androstane steroid) and dihydrotestosterone (DHT) on tissue architecture, cell proliferation and gene expression. Ovariectomised mice were treated daily for 7 days with compound or vehicle control (VC). Uterine morphometric characteristics were quantified using high-throughput image analysis (StrataQuest; TissueGnostics), protein and gene expression were evaluated by immunohistochemistry and RT-qPCR, respectively. Treatment with GTx-024, Danazol or DHT induced significant increases in body weight, uterine weight and the surface area of the endometrial stromal and epithelial compartments compared to VC. Treatment with GTx-007 had no impact on these parameters. GTx-024, Danazol and DHT all significantly increased the percentage of Ki67-positive cells in the stroma, but only GTx-024 had an impact on epithelial cell proliferation. GTx-007 significantly increased uterine expression of Wnt4 and Wnt7a, whereas GTx-024 and Danazol decreased their expression. In summary, the impact of GTx-024 and Danazol on uterine cells mirrored that of DHT, whereas GTx-007 had minimal impact on the tested parameters. This study has identified endpoints that have revealed differences in the effects of SARMs on uterine tissue and provides a template for preclinical studies comparing the impact of compounds targeting the AR on endometrial function.

Trichogramma spp., among the most common parasitoids used for augmentation biological control, often are mass-reared on eggs of the Mediterranean flour moth, Ephestia kuehniella (Zeller). To evaluate removal of nutritional components from the E. kuehniella larval diet and reduce production costs, colonies were maintained using one of three diets: a standard diet consisting of eight ingredients, a reduced diet containing whole wheat flour, glycerol, and Brewer's yeast, or a third minimal diet of only whole wheat flour. The standard diet sustained the fastest larval development, female pupae with the greatest mass, the highest level of adult emergence, and production of the most eggs per female. Eggs from moths reared as larvae on the standard or reduced diet had equivalent mass, length, and percent hatch. Females from larvae fed the minimal diet produced eggs with the least mass that were shorter and had the lowest percent hatch. Eggs from the three E. kuehniella colonies were exposed separately to Trichogramma brassicae Bezdenko females to determine their acceptance for oviposition. More of the eggs from the standard diet were parasitized by the females, eggs from the reduced and minimal diets being less acceptable. The percent emergence of the parasitoids was the same regardless of diet; however, the largest wasps emerged from the standard diet eggs and a greater proportion of them were females. Consequently, the standard E. kuehniella larval diet resulted in the highest rate of reproduction and robust eggs that produced superior T. brassicae wasps.

The method of optical wedge revealed that the optimum temperature for compatibility of hexakis(4-acetamidophenoxy)cyclotriphosphazene (ACP) and DER-331 epoxy resin is in the range of 220-260 °C. The interdiffusion time of components at these temperatures is about 30 min. The TGA and differential scanning calorimetry (DSC) methods revealed the curing temperature of 280 °С for this composition. IR spectroscopy confirmed that the reaction between the resin and ACP is completed within 10 min. According to the DSC data, a glass transition temperature of 130 °С was estimated for the cured resin. Combustion test UL-94 demonstrated that the obtained material can be assigned to the fireproof category of V-0. Burning droplets were not formed during the burning. The coke formed during the combustion of samples possessed a dense and porous structure. The shape of pores is closed, while their size is in the range of 0.2-200 µm.

When confronted with an adaptive radiation, considerable evidence is needed to resolve the evolutionary relationships of these closely related lineages. The North American genus Speyeria is one especially challenging radiation of butterflies due to potential signs of incomplete lineage sorting, ongoing hybridization, and similar morphological characters between species. Previous studies have found species to be paraphyletic and have been unable to disentangle taxa, often due to a lack of data and/or incomplete sampling. As a result, Speyeria remains unresolved. To achieve phylogenetic resolution of the genus, we conducted phylogenomic and population genomic analyses of all currently recognized North American Speyeria species, as well as several subspecies, using restriction-site-associated DNA sequencing (RADseq). Together, these analyses confirm the 16 canonical species, and clarify many internal relationships. However, a few relationships within Speyeria were poorly supported depending on the evolutionary model applied. This lack of resolution among certain taxa corroborates Speyeria is experiencing an ongoing adaptive radiation, with incomplete lineage sorting and lack of postzygotic reproductive barriers contributing to hybridization and further ambiguity. Given that many Speyeria taxa are under duress from anthropogenic factors, their legal protection must be viewed cautiously and on a case by case basis in order to properly conserve the diversity being generated.

Meibomian gland dysfunction (MGD) is the leading cause of dry eye disease and loss of ocular surface homeostasis. Increasingly, several observational clinical studies suggest that dyslipidemia (elevated blood cholesterol, triglyceride or lipoprotein levels) can initiate the development of MGD. However, conclusive evidence is lacking, and an experimental approach using a suitable model is necessary to interrogate the relationship between dyslipidemia and MGD. This systematic review discusses current knowledge on the associations between dyslipidemia and MGD. We briefly introduce a diet-induced obesity model where mice develop dyslipidemia, which can serve as a potential tool for investigating the effects of dyslipidemia on the meibomian gland. Finally, the utility of lipidomics to examine the link between dyslipidemia and MGD is considered.

Two new cycloartane glycosides, nervisides I-J, were isolated from Nervilia concolor whole plants. Their structures were unambiguously established by interpretation of their HRESIMS and 1D and 2D NMR data. These cycloartanes comprised a stereogenic center at C-24, the R configuration of which was assigned based on DFT-NMR calculations and the subsequent DP4 probability score. These compounds were tested for cytotoxicity against K562 and MCF-7 tumor cell lines, revealing mild cytotoxic activity.

The acoustic cues that guide the assignment of phrase boundaries in music (pauses and pitch movements) overlap with those that are known for speech prosody. Based on this, researchers have focused on highlighting the similarities and neural resources shared between music and speech prosody segmentation. The possibility that music-specific expectations add to acoustic cues in driving the segmentation of music into phrases could weaken this bottom-up view, but it remains underexplored. We tested for domain-specific expectations in music segmentation by comparing the segmentation of the same set of ambiguous stimuli under two different instructions: stimuli were either presented as speech prosody or as music. We measured how segmentation differed, in each instruction group, from a common reference (natural speech); thus, focusing on how instruction affected delexicalization effects (natural speech vs. transformed versions with no phonetic content) on segmentation. We saw interactions between delexicalization and instruction on most segmentation indices, suggesting that there is a music mode, different from a speech prosody mode in segmentation. Our findings highlight the importance of top-down influences in segmentation, and they contribute to rethinking the analogy between music and speech prosody.

Heavy metals in the soil of mining areas have become a primary source of pollution, which could cause deleterious health effects in people exposed through soil-plant systems via multi-pathways. A long-term field experiment under natural conditions was carried out to explore the distribution characteristic and migration law of heavy metals in a soil-wheat system of a mining area in Xuzhou. According to the second level standard of environmental quality standards for soils of China (GB 15618-1995), 30.8 g of CrCl3·6H2O, 8.3 g of Pb(CH3COO)2·3H2O, and 16.5 g of ZnSO4·7H2O were added into the soil of three experimental sites, respectively. The other experimental site with no additional compounds was used as the control site. The Cr, Pb, and Zn concentrations in the soil-wheat system were counted and their corresponding migration models were constructed. From 2014 to 2017, the mean concentrations of Cr (49.09 mg·kg-1), Pb (20.08 mg·kg-1), and Zn (39.11 mg·kg-1) in the soil of the addition sites were higher than that of the control site. The mean concentrations of Cr, Pb, and Zn in wheat of the addition sites were greater than that of the control site with the values of 3.29, 0.06, and 29 mg·kg-1. In comparison, the Cr, Pb, and Zn concentrations in the soil of all experimental sites were lower than the second level standard of environmental quality standards for soils of China (GB 15618-1995), whereas the Cr concentration exceeded its corresponding soil background value of Xuzhou in 2017. The Pb concentration in soil of the addition site was greater than its corresponding background value from 2014 to 2016. The Pb and Zn concentrations in wheat of all experimental sites were lower than the national hygienic standard for grains of China (GB2715-2005) and the national guidelines for cereals of China (NY 861-2004), but the Cr concentration significantly exceeded the national guidelines for cereals of China (NY 861-2004). By constructing the Identical-Discrepant-Contrary (IDC) gray connection models, the result showed that there was a non-linear relationship of Cr, Pb, and Zn concentrations in the soil-wheat system, and the absolute values of most correlation coefficients r were lower than 0.5 and the values of greyness f G ( r ) were more than 0.5. The curvilinear regression models could not reflect the relationship of Cr, Pb, and Zn concentrations in the soil-wheat system with the regression coefficient r 2 values far less than 1. Due to the values of regression coefficient r 2 being close to 1, this study suggested that the allocation estimation models could be used for simulating the Cr, Pb, and Zn migration in the soil-wheat system of a mining area in Xuzhou.

'Foamy' alveolar macrophages (FAM) observed in nonclinical toxicology studies during inhaled drug development may indicate drug-induced phospholipidosis, but can also derive from adaptive non-adverse mechanisms. Orally administered amiodarone is currently used as a model of pulmonary phospholipidosis and it was hypothesized that aerosol administration would produce phospholipidosis-induced FAM that could be characterized and used in comparative inhalation toxicology. Han-Wistar rats were given amiodarone via (1) intranasal administration (6.25 mg/kg) on two days, (2) aerosol administration (3 mg/kg) on two days, (3) aerosol administration (10 mg/kg) followed by three days of 30 mg/kg or (4) oral administration (100 mg/kg) for 7 days. Alveolar macrophages in bronchoalveolar lavage were evaluated by differential cell counting and high content fluorescence imaging. Histopathology and mass-spectrometry imaging (MSI) were performed on lung slices. The higher dose aerosolised amiodarone caused transient pulmonary inflammation (p < 0.05), but only oral amiodarone resulted in FAM (p < 0.001). MSI of the lungs of orally treated rats revealed a homogenous distribution of amiodarone and a putative phospholipidosis marker, di-22:6 bis-monoacylglycerol, throughout lung tissue whereas aerosol administration resulted in localization of both compounds around the airway lumen. Thus, unlike oral administration, aerosolised amiodarone failed to produce the expected FAM responses.

The Western dietary pattern can alter the gut microbiome and cause obesity and metabolic disorders. To examine the interactions between diet, the microbiome, and obesity, we transplanted gut microbiota from lean or obese human donors into mice fed one of three diets for 22 weeks: (1) a control AIN93G diet; (2) the total Western diet (TWD), which mimics the American diet; or (3) a 45% high-fat diet-induced obesity (DIO) diet. We hypothesized that a fecal microbiome transfer (FMT) from obese donors would lead to an obese phenotype and aberrant glucose metabolism in recipient mice that would be exacerbated by consumption of the TWD or DIO diets. Prior to the FMT, the native microbiome was depleted using an established broad-spectrum antibiotic protocol. Interestingly, the human donor body type microbiome did not significantly affect final body weight or body composition in mice fed any of the experimental diets. Beta diversity analysis and linear discriminant analysis with effect size (LEfSe) showed that mice that received an FMT from obese donors had a significantly different microbiome compared to mice that received an FMT from lean donors. However, after 22 weeks, diet influenced the microbiome composition irrespective of donor body type, suggesting that diet is a key variable in the shaping of the gut microbiome after FMT.

The prevalence of cognitive impairments and circadian disturbances increases in the elderly and Alzheimer's disease (AD) patients. This study investigated the effects of a standardized extract of Asparagus officinalis stem, ETAS® on cognitive impairments and circadian rhythm status in senescence-accelerated mice prone 8 (SAMP8). ETAS® consists of two major bioactive constituents: 5-hydroxymethyl-2-furfural (HMF), an abundant constituent, and (S)-asfural, a novel constituent, which is a derivative of HMF. Three-month-old SAMP8 male mice were divided into a control, 200 and 1000 mg/kg BW ETAS® groups, while senescence-accelerated resistant mice (SAMR1) were used as the normal control. After 12-week feeding, ETAS® significantly enhanced cognitive performance by an active avoidance test, inhibited the expressions of amyloid-beta precursor protein (APP) and BACE-1 and lowered the accumulation of amyloid β (Aβ) in the brain. ETAS® also significantly increased neuron number in the suprachiasmatic nucleus (SCN) and normalized the expressions of the melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). In conclusion, ETAS® enhances the cognitive ability, inhibits Aβ deposition and normalizes circadian rhythm signaling, suggesting it is beneficial for preventing cognitive impairments and circadian rhythm disturbances in aging.

The relationship between body weight and different cancers is now well-recognized and among such cancers, colorectal cancer (CRC) is reported most frequently. Our group recently published findings, through an epigenome-wide association study, suggesting that body mass index (BMI) could act as a relevant risk factor in the CRC. In addition, aberrant SFRP2 methylation is one of the major mechanisms for Wnt signaling activation in CRC. Conversely, neoadjuvant chemo-radiotherapy appears to alter the rectal cancer epigenome. This study was aimed to evaluate the effect of obesity, measured by BMI, on the methylation of SFRP2 in tumor samples of patients with CRC. Non-treated CRC patients and CRC patients treated with pre-operative neoadjuvant therapy from 2011 to 2013 were included and classified by BMI < 25.0 kg/m2 and BMI > 25.0 kg/m2. SFRP2 DNA methylation in tumor samples was measured by pyrosequencing. Our findings suggest a possible interaction between SFRP2 methylation levels and BMI in CRC tumor samples. The correlation of SFRP2 hypomethylation with an elevated BMI was stronger within the non-treated CRC patient group than within the treated CRC patient group. We have successfully demonstrated that the beneficial association of tumor SFRP2 hypomethylation is dependent on patient BMI in non-treated CRC, suggesting a possible tumor suppressor role for SFRP2 in overweight and obese patients. Additional studies of clinical pathologies would be necessary to strengthen these preliminary results.

Natural products derived from plants play a vital role in the discovery of new drug candidates, and these are used for novel therapeutic drug development. Andrographis paniculata and Spilanthes paniculata are used extensively as medicinal herbs for the treatment of various ailments, and are reported to have neuroprotective properties. β-amyloid is a microscopic brain protein whose significant aggregation is detected in mild cognitive impairment and Alzheimer's disease (AD) brains. The accumulation of β-amyloid disrupts cell communication and triggers inflammation by activating immune cells, leading to neuronal cell death and cognitive disabilities. The proteases acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta secretase-1 (BACE-1) have been reported to be correlated with the synthesis and growth of β-amyloid plaques in the brains of AD patients. In the present study, the phenolic compounds from A. paniculata and S. paniculata that have been reported in the literature were selected for the current investigation. Furthermore, we employed molecular docking and molecular dynamics studies of the phenolic compounds with the proteins AChE, BChE, and BACE-1 in order to evaluate the binding characteristics and identify potent anti-amyloid agents against the neurodegenerative diseases such as AD. In this investigation, we predicted three compounds from A. paniculata with maximum binding affinities with cholinesterases and BACE-1. The computational investigations predicted that these compounds follow the rule of five. We further evaluated these molecules for in vitro inhibition activity against all the enzymes. In the in vitro investigations, 3,4-di-o-caffeoylquinic acid (5281780), apigenin (5280443), and 7-o-methylwogonin (188316) were found to be strong inhibitors of AChE, BChE, and BACE-1. These findings suggest that these compounds can be potent multi-target inhibitors of the proteases that might cumulatively work and inhibit the initiation and formation of β-amyloid plaques, which is a prime cause of neurotoxicity and dementia. According to our knowledge, these findings are the first report on natural compounds isolated from A. paniculata as multi-target potent inhibitors and anti-amyloid agents.

Influenza A viruses leading to infectious respiratory diseases cause seasonal epidemics and sometimes periodic global pandemics. Viral polymerase is an attractive target in inhibiting viral replication, and 4'-ethynyladenosine, which has been reported as a highly potent anti-human immunodeficiency virus (HIV) nucleoside derivative, can work as an anti-influenza agent. Herein, we designed and synthesized a 4'-ethynyl-2'-deoxyadenosine 5'-monophosphate analog called EdAP (5). EdAP exhibited potent inhibition against influenza virus multiplication in Madin-Darby canine kidney (MDCK) cells transfected with human α2-6-sialyltransferase (SIAT1) cDNA and did not show any toxicity toward the cells. Surprisingly, this DNA-type nucleic acid analog (5) inhibited the multiplication of influenza A virus, although influenza virus is an RNA virus that does not generate DNA.

Anorexia Nervosa (AN) is a psychiatric disorder characterised by a physical and psychosocial deterioration due to an altered pattern on the intake and weight control. The severity of the disease is based on the degree of malnutrition. The objective of this article is to review the scientific evidence of the refeeding process of malnourished inpatients with AN; focusing on the clinical outcome.

:Background: Current diagnosis and staging of advanced epithelial ovarian cancer (aEOC) has important limitations and better biomarkers are needed. We investigate the performance of non-haematopoietic circulating cells (CCs) at the time of disease presentation and relapse. Methods: Venous blood was collected prospectively from 37 aEOC patients and 39 volunteers. CCs were evaluated using ImageStream TechnologyTM and specific antibodies to differentiate epithelial cells from haematopoetic cells. qRT-PCR from whole blood of relapsed aEOC patients was carried out for biomarker discovery. Results: Significant numbers of CCs (CK+/WT1+/CD45-) were identified, quantified and characterised from aEOC patients compared to volunteers. CCs are abundant in women with newly diagnosed aEOC, prior to any treatment. Evaluation of RNA from the CCs in relapsed aEOC patients (n = 5) against a 79-gene panel revealed several differentially expressed genes compared to volunteers (n = 14). Size differentiation of CCs versus CD45+ haematopoietic cells was not reliable. Conclusion: CCs of non-haematopoetic origin are prevalent, particularly in patients with newly diagnosed aEOC. Exploiting a CC-rich population in aEOC patients offers insights into a part of the circulating microenvironment.

Peptides from fish may beneficially affect several metabolic outcomes, including gut health and inflammation. The effect of fish peptides in subjects with irritable bowel syndrome (IBS) has not previously been investigated, hence this study aimed to evaluate the effect of a cod protein hydrolysate (CPH) supplement on symptom severity, gut integrity markers and fecal fermentation in IBS-patients. A double-blind, randomized parallel-intervention with six weeks of supplementation with 2.5 g CPH (n = 13) or placebo (n = 15) was conducted. The outcomes were evaluated at baseline and the end of the study. The primary outcomes were symptom severity evaluated by the IBS severity scoring system (IBS-SSS) and quality of life. The secondary outcomes included gut integrity markers and pro-inflammatory cytokines in serum, fecal fermentation measured by concentration of short-chain fatty acids (SCFAs) and fecal calprotectin. The groups were comparable at baseline. The total IBS-SSS-scores were reduced in both the CPH-group (298 ± 69 to 236 ± 106, p = 0.081) and the placebo-group (295 ± 107 to 202 ± 103, p = 0.005), but the end of study-scores did not differ (p = 0.395). The concentrations of serum markers and SCFAs did not change for any of the groups. The baseline measures for the whole group showed that the total SCFA concentrations were inversely correlated with the total IBS-SSS-score (r = -0.527, p = 0.004). Our study showed that a low dose of CPH taken daily by IBS-patients for six weeks did not affect symptom severity, gut integrity markers or fecal fermentation when compared to the placebo group.

Conventional oral administration of antifilariasis drugs results in nonspecific targeting of the drugs and the intradermal delivery of nanoparticles with sizes of <100 nm could be used to improve lymphatic uptake. This study investigated the combination of nanosuspension and dissolving microneedles (MN-NS) as an alternative intradermal delivery approach for the delivery of antifilariasis drugs, namely doxycycline, albendazole, and ivermectin. NS were fabricated and optimized using a bottom-up technique. The NS were then incorporated into the MN arrays. The optimized NS were <100 nm in diameter. Furthermore, MN-NS had suitable mechanical strength and insertion capabilities. The dermatokinetic study revealed that the delivery of drugs into the dermis of excised neonatal porcine skin by MNs was significantly higher than that from a needle-free patch, with 29.29 ± 4.65%, 31.54 ± 5.35%, and 34.54 ± 4.98% of doxycycline, albendazole sulfoxide, and ivermectin retained in the dermis after 24 h. The results presented here serve as proof of concept for the significant enhancement of drug retention times in the dermis, following their formulation into NS and delivery via MN. Leading on from these studies, future work must investigate in vivo lymphatic pharmacokinetic profiling of drugs formulated into NS, in a suitable animal model.

Cholesterol-enriched functional portions of plasma membranes, such as caveolae and rafts, were isolated from lungs of wild-type (WT) and caveolin-1 knockout (Cav-1 KO) mice within detergent resistant membranes (DRMs). To gain insight into their molecular composition we performed proteomic and lipid analysis on WT and Cav-1 KO-DRMs that showed predicted variations of proteomic profiles and negligible differences in lipid composition, while Langmuir monolayer technique and small and wide-angle X-ray scattering (SAXS-WAXS) were here originally introduced to study DRMs biophysical association state. Langmuir analysis of Cav-1 containing DRMs displayed an isotherm with a clear-cut feature, suggesting the coexistence of the liquid-ordered (Lo) phase typical of the raft structure, namely "cholesterol-rich Lo phase," with a phase fully missing in Cav-1 KO that we named "caveolin-induced Lo phase." Furthermore, while the sole lipid component of both WT and KO-DRMs showed qualitatively similar isotherm configuration, the reinsertion of recombinant Cav-1 into WT-DRMs lipids restored the WT-DRM pattern. X-ray diffraction results confirmed that Cav-1 causes the formation of a "caveolin-induced Lo phase," as suggested by Langmuir experiments, allowing us to speculate about a possible structural model. These results show that the unique molecular link between Cav-1 and cholesterol can spur functional order in a lipid bilayer strictly derived from biological sources.