To compare etonogestrel pharmacokinetic and pharmacodynamic outcomes by both self-reported race/ethnicity and genetically determined ancestry among contraceptive implant users. We conducted a secondary analysis of our parent pharmacogenomic study of 350 implant users. We genotyped these reproductive-aged (18-45 years) women for 88 ancestry-informative single nucleotide polymorphisms. We then assigned each participant a proportion value for African (AFR), European (EUR), and Indigenous American (AMR) ancestry based on reference population data. We correlated genetic ancestry with self-reported race/ethnicity and utilized genetic ancestry proportion values as variables for previously performed association analyses with serum etonogestrel concentrations and progestin-related side effects (e.g., bothersome bleeding and subjective weight gain). We successfully estimated genetically determined ancestry for 332 participants. EUR, AFR, and AMR ancestry were each highly correlated with self-reported White/non-Hispanic race (r = 0.64, p = 4.14 × 10-40 ), Black/African American race (r = 0.88, p = 1.36 × 10-107 ), and Hispanic/Latina ethnicity (r = 0.68, p = 4.03 × 10-47 ), respectively. Neither genetically determined ancestry nor self-reported race/ethnicity were significantly associated with serum etonogestrel concentrations. AFR ancestry and self-reported Black race had similar associations with reporting monthly periods (odds ratio [OR] 2.18, p = 0.09 vs. OR 2.22, p = 0.02) and having received treatment for bothersome bleeding (OR 5.19, p = 0.005 vs. OR 4.73, p = 2.0 × 10-4 ). In multivariable logistic regression for subjective weight gain, AMR ancestry dropped out of the model in preference for self-reported Hispanic/Latina ethnicity. We found no new associations between genetically determined ancestry and contraceptive implant pharmacodynamics/pharmacokinetics. Self-reported race/ethnicity were strong surrogates for genetically determined ancestry among this population of contraceptive implant users. Our data suggest that self-reported race/ethnicity, capturing societal and cultural aspects, remain important to the investigation of progestin-related side effects.

The correlation between triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio variability and incident diabetes has not been fully elucidated. We aimed to characterize the relationship between TG/HDL-C ratio variability and new-onset diabetes in Chinese adults.

It has been shown previously both in vitro and in vivo that microbeam irradiation (MBI) can control malignant tumour cells more effectively than the clinically established concepts of broad beam irradiation. With the aim to extend the international capacity for microbeam research, the first MBI experiment at the biomedical beamline SYRMEP of the Italian synchrotron facility ELETTRA has been conducted. Using a multislit collimator produced by the company TECOMET, arrays of quasi-parallel microbeams were successfully generated with a beam width of 50 µm and a centre-to-centre distance of 400 µm. Murine melanoma cell cultures were irradiated with a target dose of approximately 65 Gy at a mean photon energy of ∼30 keV with a dose rate of 70 Gy s-1 and a peak-to-valley dose of ∼123. This work demonstrated a melanoma cell reduction of approximately 80% after MBI. It is suggested that, while a high energy is essential to achieve high dose rates in order to deposit high treatment doses in a short time in a deep-seated target, for in vitro studies and for the treatment of superficial tumours a spectrum in the lower energy range might be equally suitable or even advantageous.

X-rays are emerging as a complementary probe to visible-light photons and electrons for imaging biological cells. By exploiting their small wavelength and high penetration depth, it is possible to image whole, intact cells and resolve subcellular structures at nanometer resolution. A variety of X-ray methods for cell imaging have been devised for probing different properties of biological matter, opening up various opportunities for fully exploiting different views of the same sample. Here, a combined approach is employed to study cell nuclei of NIH-3T3 fibroblasts. Scanning small-angle X-ray scattering is combined with X-ray holography to quantify length scales, aggregation state, and projected electron and mass densities of the nuclear material. Only by joining all this information is it possible to spatially localize nucleoli, heterochromatin and euchromatin, and physically characterize them. It is thus shown that for complex biological systems, like the cell nucleus, combined imaging approaches are highly valuable.

The aim of the present study was to explore the mechanism by which microRNA (miR)‑642a‑5p regulates the migration and invasion of colon cancer cells via collagen type I α1 (COL1A1). The characteristics of miR‑642a‑5p and COL1A1 were analysed through bioinformatics. Cancer and normal tissues were collected from patients with colon cancer. miR‑642a‑5p‑ and COL1A1‑overexpressing cell lines were constructed by transfection. A dual‑luciferase reporter assay was used to verify the targeting of COL1A1 by miR‑642a‑5p. Cell Counting Kit‑8, wound healing and Transwell assays were used to detect cell viability, migration and invasion, respectively. Protein and mRNA expression levels were examined by western blotting and reverse transcription‑quantitative PCR, respectively. The results revealed that miR‑642a‑5p expression was significantly upregulated and COL1A1 expression was downregulated in patients with colon cancer. Low levels of miR‑642a‑5p and high levels of COL1A1 were associated with a poor prognosis in patients with colon cancer. miR‑642a‑5p directly targeted the 3'‑untranslated region of COL1A1 and inhibited COL1A1 expression. Overexpression of miR‑642a‑5p inhibited cell viability, migration, invasion and epithelial mesenchymal transition. Overexpression of COL1A1 promoted cell viability, migration, invasion and EMT, and partially reversed the inhibitory effects of miR‑642a‑5p on colon cancer cells. In conclusion, miR‑642a‑5p inhibited colon cancer cell migration, invasion and EMT by regulating COL1A1.

Long non‑coding RNA (lncRNA) actin filament‑associated protein 1 antisense RNA 1 (AFAP1‑AS1) has been reported to serve important roles in multiple types of cancer. However, the biological function and underlying mechanism of AFAP1‑AS1 in oral squamous cell carcinoma (OSCC) remain largely unknown. The present study aimed to investigate the biological roles and clarify the potential mechanism of AFAP1‑AS1 in OSCC. The expression levels of AFAP1‑AS1 in OSCC tissues and cells were determined using reverse transcription‑quantitative PCR. Cell proliferation, colony formation, migration and invasion were analyzed using Cell Counting Kit‑8, colony formation, wound healing and Transwell invasion assays, respectively. The potential binding between AFAP1‑AS1 and microRNA (miR)‑145 was validated using dual luciferase reporter and RNA pull‑down assays. A xenograft tumor model was established to evaluate the effect of AFAP1‑AS1 in vivo. The results revealed that AFAP1‑AS1 expression levels were markedly upregulated in OSCC tissues and cells. In addition, patients with OSCC with high expression levels of AFAP1‑AS1 had a poor prognosis. Functionally, the knockdown of AFAP1‑AS1 in OSCC cells significantly inhibited cell proliferation, migration and invasion in vitro. Similarly, in vivo AFAP1‑AS1 knockdown prevented tumor growth and reduced tumor size and weight. Mechanistically, AFAP1‑AS1 was discovered to regulate the expression levels of Homeobox A1 (HOXA1) by competing with miR‑145. The inhibition of miR‑145 partially attenuated the inhibitory effects of AFAP1‑AS1 knockdown on OSCC cells. In conclusion, the findings of the present study suggested that AFAP1‑AS1 may promote the progression of OSCC by regulating the miR‑145/HOXA1 axis.

Glioma is the most aggressive tumor of the central nervous system. Long non‑coding RNAs (lncRNAs) may be involved in modulating tumor generation. The present study analyzed an lncRNA microarray of glioma and selected long intergenic non‑protein coding RNA 665 (LINC00665) as the research object. The mode of expression and biological function of LINC00665 in glioma were assessed using lncRNA microarray and RT‑qPCR analyses. Gain‑of‑function assays and/or loss‑of‑function assays were implemented to explore the role of LINC00665 in the progression of glioma. Dual‑luciferase reporter and RNA immunoprecipitation assays explored the downstream molecular mechanism of LINC00665. The function of the molecular pathway in progression of glioma was analyzed using rescue assays. High expression of LINC00665 was marked in glioma tissues and cells, which correlated with an unsatisfactory prognosis. Upregulation of LINC00665 significantly promoted the proliferation and invasion of glioma cells. LINC00665 acted as a competing endogenous RNA by sponging miR‑34a‑5p to upregulate angiotensin II receptor type 1 (AGTR1). LINC00665 promoted the progression of glioma by acting as a competitive endogenous RNA to competitively bind to miR‑34a‑5p and mediate AGTR1 expression.

Ubiquitin-specific protease 7 (USP7) belongs to the group of deubiquitinating enzymes (DUBs), which remove ubiquitin which controls various cellular processes such as chromosome segregation, DNA repair, gene expression, protein localization, kinase activity, protein degradation, cell cycle progression, and apoptosis. It is critical for several important functions in the cell, and therefore dysregulation of USP7 can contribute to tumorigenesis.

The aim of the current study was to explore the whole-brain dynamic functional connectivity patterns in acute ischemic stroke (AIS) patients and their relation to short and long-term stroke severity. We investigated resting-state functional MRI-based dynamic functional connectivity of 41 AIS patients two to five days after symptom onset. Re-occurring dynamic connectivity configurations were obtained using a sliding window approach and k-means clustering. We evaluated differences in dynamic patterns between three NIHSS-stroke severity defined groups (mildly, moderately, and severely affected patients). Furthermore, we built Bayesian hierarchical models to evaluate the predictive capacity of dynamic connectivity and examine the interrelation with clinical measures, such as white matter hyperintensity lesions. Finally, we established correlation analyses between dynamic connectivity and AIS severity as well as 90-day neurological recovery (ΔNIHSS). We identified three distinct dynamic connectivity configurations acutely post-stroke. More severely affected patients spent significantly more time in a configuration that was characterized by particularly strong connectivity and isolated processing of functional brain domains (three-level ANOVA: p < .05, post hoc t tests: p < .05, FDR-corrected). Configuration-specific time estimates possessed predictive capacity of stroke severity in addition to the one of clinical measures. Recovery, as indexed by the realized change of the NIHSS over time, was significantly linked to the dynamic connectivity between bilateral intraparietal lobule and left angular gyrus (Pearson's r = -.68, p = .003, FDR-corrected). Our findings demonstrate transiently increased isolated information processing in multiple functional domains in case of severe AIS. Dynamic connectivity involving default mode network components significantly correlated with recovery in the first 3 months poststroke.

Neural and behavioral mechanisms during approach-avoidance conflict decision-making are relevant across various psychiatric disorders, particularly anxiety disorders. Studies using approach-avoidance conflict paradigms in healthy adults have identified preliminary neural mechanisms, but findings must be replicated and demonstrated as reliable before further application. This study sought to replicate previous findings and examine test-retest reliability of behavioral (approach behavior, reaction time) and neural (regions of interest [ROIs]) responses during an approach-avoidance conflict task conducted during functional magnetic resonance imaging (fMRI). Thirty healthy adults completed an approach-avoidance conflict task during fMRI on two occasions (mean interval: 17 days; range: 11-32). Effects of task condition during three task phases (decision-making, affective outcome and monetary reward) and intraclass correlation coefficients (ICCs) were calculated across time points. Results replicated that approach behavior was modulated by conflict during decision-making. ROI activations were replicated such that dorsal anterior cingulate cortex (dACC) was modulated by conflict during decision-making, and dACC, striatum, and anterior insula were modulated by valence during affective outcomes (p's <.0083). Approach behavior during conflict demonstrated excellent reliability (ICCs ≥.77). Activation of dACC during conflict decision-making and anterior insula during negative outcomes demonstrated fair reliability (ICCs = .51 and .54), and dACC and striatum activation demonstrated good reliability during negative outcomes (ICCs = .63 and .69). Two additional ROIs (amygdala, left dorsolateral prefrontal cortex) showed good reliability during negative outcomes (ICCs ≥.60). These results characterize several specific behavioral and neuroimaging responses that are replicable and sufficiently reliable during approach-avoidance conflict decision-making to support future utility.

Mild cognitive impairment due to semantic dementia represents the preclinical stage, involving cognitive decline dominated by semantic impairment below the semantic dementia standard. Therefore, studying mild cognitive impairment due to semantic dementia may identify changes in patients before progression to dementia. However, whether changes in local functional activity occur in preclinical stages of semantic dementia remains unknown. Here, we explored local functional changes in patients with mild cognitive impairment due to semantic dementia using resting-state functional MRI.

Athletes train to improve strength and endurance to demonstrate maximum performance during competitions. Training methods vary but most focus on strength, endurance, or both. Concurrent training is a combination of two different modes of training. In this study, we combined resistance exercise (RE) and high-intensity interval exercise (HIIE) to investigate the influence of the order of the concurrent training on signal molecules on hypertrophy and glycolysis in the skeletal muscle. The phosphorylation levels of mechanistic target of rapamycin (mTOR) signals, p70 S6 kinase (p70S6 K), ribosomal protein S6 (S6), and glycogen synthase kinase beta (GSK-3β) were significantly increased in the HIIE first group compared with the control group. The combined training course did not affect the glycogen content and expression levels of proteins concerning glycolytic and metabolic capacity, suggesting that a combination of HIIE and RE on the same day, with HIIE prior to RE, improves hypertrophy response and glycolysis enhancement.

Hyperbaric exposure (1.3 atmospheres absolute with 20.9% O2 ) for 1 h a day was shown to improve exercise capacity. The present study was designed to reveal whether the daily exposure time affects exercise performance and metabolism in skeletal and cardiac muscles. Male mice in the training group were housed in a cage with a wheel activity device for 7 weeks from 5 weeks old. Trained mice were then subjected to hybrid training (HT, endurance exercise for 30 min followed by sprint interval exercise for 30 min). Hyperbaric exposure was applied following daily HT for 15 min (15HT), 30 min (30HT), or 60 min (60HT) for 4 weeks. In the endurance capacity test, maximal work values were significantly increased by 30HT and 60HT. In the left ventricle (LV), activity levels of 3-hydroxyacyl-CoA-dehydrogenase, citrate synthase, and carnitine palmitoyl transferase (CPT) 2 were significantly increased by 60HT. CPT2 activity levels were markedly increased by hyperbaric exposure in red gastrocnemius (Gr) and plantaris muscle (PL). Pyruvate dehydrogenase complex activity values in PL were enhanced more by 30HT and 60HT than by HT. Protein levels of N-terminal isoform of PGC1α (NT-PGC1α) protein were significantly enhanced in three hyperbaric exposed groups in Gr, but not in LV. These results indicate that hyperbaric exposure for 30 min or longer has beneficial effects on endurance, and 60-min exposure has the potential to further increase performance by facilitating fatty acid metabolism in skeletal and cardiac muscles in highly trained mice. NT-PGC1α may have important roles for these adaptations in skeletal muscle.

In the present study, we examined the tolerance-inducing effects of human adipose-derived mesenchymal stem cells (hAD-MSCs) and bone marrow-derived MSCs (hBM-MSCs) on a nonhuman primate model of skin transplantation.

Although growing evidences have showed that long non-coding RNA (lncRNAs) plasmacytoma variant translocation 1 (PVT1) plays a critical role in the progression of non-small cell lung cancer (NSCLC), there are still many unsolved mysteries remains to be deeply elucidated. This study aimed to find a new underlying mechanism of PVT1 in regulating the tumorigenesis and development of NSCLC.

Atherosclerosis (AS) is one of the most common causes of human death and disability. This study is designed to investigate the roles of aldosterone (Aldo) and oxidized low-density lipoprotein (Ox-LDL) in this disease by clinical data and cell model.

Functional cardiac tissue engineering holds promise as a candidate approach for myocardial infarction. Tissue engineering has emerged to generate functional tissue constructs and provide an alternative means to repair and regenerate damaged heart tissues.

A wide range of pharmaceuticals and endocrine disrupting compounds enter freshwaters globally. As these contaminants are transported through aquatic food webs, understanding their impacts on both aquatic and terrestrial ecosystems remains a major challenge. Here, we provide the first direct evidence of the transfer of pharmaceuticals and endocrine disruptors through the aquatic-terrestrial habitat linkage by emerging aquatic insects. We also show that the type of insect metamorphosis and feeding behavior determine the bioaccumulation patterns of these contaminants. Adult Trichoptera, an important food source for riparian predators, showed an increased body burden of pharmaceuticals and endocrine disruptors. This implies that terrestrial predators, such as spiders, birds, and bats, are exposed to mixtures of pharmaceuticals and endocrine disruptors of aquatic origin, which may impact their physiology and population dynamics. Overall, our study provides valuable insights into the bioaccumulation patterns and trophic cross-ecosystem transfer of these contaminants, from aquatic primary producers to terrestrial predators.

Liquid-like condensates have been thought to be sphere-like. Recently, various condensates with filamentous morphology have been observed in cells. One such condensate is the TIS granule network that shares a large surface area with the rough endoplasmic reticulum and is important for membrane protein trafficking. It has been unclear how condensates with mesh-like shapes but dynamic protein components are formed. In vitro and in vivo reconstitution experiments revealed that the minimal components are a multivalent RNA-binding protein that concentrates RNAs that are able to form extensive intermolecular mRNA-mRNA interactions. mRNAs with large unstructured regions have a high propensity to form a pervasive intermolecular interaction network that acts as condensate skeleton. The underlying RNA matrix prevents full fusion of spherical liquid-like condensates, thus driving the formation of irregularly shaped membraneless organelles. The resulting large surface area may promote interactions at the condensate surface and at the interface with other organelles.

The web-based EatWellQ8 food frequency questionnaire (FFQ) was developed as a dietary assessment tool for healthy adults in Kuwait. Validation against reliable instruments and assessment of its reproducibility are required to ensure the accuracy of the EatWellQ8 FFQ in computing nutrient intake.