Cancer progression is commonly segregated into processes of primary tumour growth and secondary metastasis. Recent evidence suggests that a subpopulation of cancer cells, cancer stem cells (CSCs), is ...responsible for tumour growth in cancer. However, the role of CSCs in cancer metastasis is unclear. In this study, we found that the C terminus of CD44 contributes to sphere formation and survival in vitro via the CD44–SRC–integrin axis. In addition, nuclear CD44/acetylated‐STAT3 is required for clonal formation in vitro and tumourigenicity in vivo. Nuclear CD44 binds to various promoters identified by chromatin immunoprecipitation‐seq, including that of c‐myc and Twist1, leading to cell fate change through transcriptional reprogramming. We propose that nuclear CD44/acetylated‐STAT3 performs an unexpected tumour‐progressing function by enhancing cell outgrowth into structures where cells with properties of CSCs can be generated from differentiated somatic cells in suspension culture, and then exhibit attributes of cells that have undergone an epithelial–mesenchymal transition, leading to tumour metastasis, and a resulting worse prognosis.
CD44 is a known marker for cancer stem cells (CSCs) and had functionally been associated with cancer metastasis. This paper highlights the functional contribution of CD44 in determining cellular features of CSCs that include the definition of underlying molecular mechanisms.
Various biofuels, including bioethanol and biodiesel are technologically being considered replacements for fossil fuels, such as the conventional gasoline and diesel. This paper aims to measure ...whether economic substitutability can be generated during periods of higher and/or lower prices of crude oil. The empirical results of the bivariate EGARCH model prove that this substitutive effect was occurred during the higher crude oil price period due to the significant price spillover effects from crude oil futures to corn and soybean futures, indicating that the increase in food prices can be attributed to more consumption of biofuels. We suggest more extensive research in the search for fuel alternatives from inedible feedstock such as pongamia, jojoba, jatropha, especially the 2nd generation biofuel technologies such as algae-based biofuels.
Schizophrenia and substance involvement frequently co‐occur in individuals, and a bidirectional relationship between the two has been proposed; shared underlying genetic factors could be an ...alternative explanation. This study investigated the genetic overlap between schizophrenia and substance involvement, including tobacco, alcohol and betel nut use. The study subjects were recruited from the Taiwan Biobank, and genome‐wide genotyping data was available for 18 327 participants without schizophrenia. We calculated the Psychiatric Genomics Consortium‐derived polygenic risk score (PRS) for schizophrenia in each participant. The significance of the schizophrenia PRS associated with substance involvement was evaluated using a regression model with adjustments for gender, age and population stratification components. The modified effect of gender or birth decade was also explored. The schizophrenia PRS was positively associated with lifetime tobacco smoking in women (OR in per SD increase in PRS = 1.12 with 95% CI 1.04‐1.20, P = .002), but not in men (OR = 0.99 with 95% CI 0.95‐1.04, P = .74), and the gender‐PRS interaction reached significance (P = .006). The OR between PRS and lifetime tobacco smoking increased with the birth decade (P of birth decade‐PRS interaction = .0002). In women, OR increased from 0.97 (P = .85) for subjects with a birth decade before 1950 to 1.21 (P = .04) for subjects with a birth decade after 1980; in men, the corresponding OR increased from 0.88 (P = .04) to 1.13 (P = .11). There was no association between schizophrenia PRS and alcohol/betel nut use phenotypes. This study provides evidence for the genetic overlap between schizophrenia and tobacco use in women, and this overlap was stronger in the younger population.
This study provided evidence for the genetic overlap between schizophrenia and tobacco smoking in women, and this overlap was stronger in younger subjects.
First-line anti-tuberculosis (TB) drugs are commonly used to treat TB worldwide, leading to more contaminated wastewater being widely discharged into aquatic environments. However, studies of mixture ...interactions of anti-TB drugs and their residues in aquatic environments are scarce. This study aimed to determine the toxic interactions of anti-TB drugs—isoniazid (INH), rifampicin (RMP), and ethambutol (EMB)—in binary and ternary mixtures on Daphnia magna and used the epidemiology of TB history to construct epidemiology-based wastewater monitoring for assessing the environmental release of residues and related ecological risks. The acute immobilization of median effect concentrations (EC50) was 25.6 mg L−1 for INH, 80.9 mg L−1 for RMP, and 188.8 mg L−1 for EMB, as toxic units (TUs) for assessing mixture toxicity. The ternary mixture exhibited the lowest TUs at 50 % effects with 1.12, followed by 1.28 for RMP + EMB, 1.54 for INH + RMP, and 1.93 for INH + EMB, indicating antagonistic interactions. Nevertheless, the combination index (CBI) was used to examine the mixture toxicity in response to immobilization, revealing that the ternary mixture of CBI ranged from 1.01 to 1.08, tending to have a nearly additive effect when suffering >50 % effect (at high concentration levels). The forecasted environmentally relevant concentrations of anti-TB drugs have been on downward trends with ng L−1 level from 2020 to 2030 in Kaohsiung, Taiwan. Although ecotoxicological risks from the wastewater treatment plant and receiving water in the field were slightly greater than the prediction from epidemiology-based wastewater monitoring, there were no risk concerns. Here, we achieved the establishment of evidence that anti-TB drug mixtures' interaction and epidemiological-based monitoring support a systematic approach, resolving the absence of the mixture toxicity information for anti-TB mixture risk assessment in aquatic environments.
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•Binary anti-TB drug mixtures exhibited antagonistic interactions.•Ternary anti-TB drug mixture tended to be antagonistic and nearly had an additive effect.•Concentration of anti-TB drugs was estimated from epidemiology-based wastewater monitoring.•There were no ecological risk concerns in anti-TB drug mixtures.
With the improvement of the survival rate of acute lymphoblastic leukemia (ALL) in children, some children ALL survivors reveal inferior intellectual and cognition outcome. Methotrexate (MTX), while ...serving as an essential component in ALL treatment, has been reported to be related to various neurologic sequelae. Using combined intrathecal (IT) and intraperitoneal (IP) MTX model, we had demonstrated impaired spatial memory function in developing rats, which can be rescued by melatonin treatment. To elucidate the impact of MTX treatment on the epigenetic modifications of the myelination process, we examined the change of neurotrophin and myelination-related transcriptomes in the present study and found combined IT and IP MTX treatment resulted in altered epigenetic modification on the myelination process, mainly in the hippocampus. Further, melatonin can restore the MTX effect through alterations of the epigenetic pathways.
MiRNAs play essential roles in plant development and response to biotic and abiotic stresses through interaction with their target genes. The expression level of miRNAs shows great variations among ...different plant accessions, developmental stages, and tissues. Little is known about the content within the plant genome contributing to the variations in plants. This study aims to identify miRNA expression-related quantitative trait loci (miR-QTLs) in the maize genome.
The miRNA expression level from next generation sequencing (NGS) small RNA libraries derived from mature leaf samples of the maize panel (200 maize lines) was estimated as phenotypes, and maize Hapmap v3.2.1 was chosen as the genotype for the genome-wide association study (GWAS). A total of four significant miR-eQTLs were identified contributing to miR156k-5p, miR159a-3p, miR390a-5p and miR396e-5p, and all of them are trans-eQTLs. In addition, a strong positive coexpression of miRNA was found among five miRNA families. Investigation of the effects of these miRNAs on the expression levels and target genes provided evidence that miRNAs control the expression of their targets by suppression and enhancement.
These identified significant miR-eQTLs contribute to the diversity of miRNA expression in the maize penal at the developmental stages of mature leaves in maize, and the positive and negative regulation between miRNA and its target genes has also been uncovered.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Some personality traits, especially neuroticism, has been found to be associated with suicide attempt (SA) in mood disorder patients. The present study explored the association between personality ...traits and SA using polygenic risk scores (PRS) for personality among patients with mood disorders. We also investigated the effects of a variety of psychosocial variables on SA. Patients with bipolar disorder (BPD, N = 841) and major depressive disorder (MDD, N = 710) were recruited from hospitals in Taiwan. Lifetime SA and information on psychosocial factors was collected. We calculated the PRS of neuroticism and extraversion. A trend test for SA was performed across quartiles of the PRS for neuroticism and extraversion, and logistic regression analyses were performed to examine the associations between psychosocial factors and SA, accounting for the PRS of personality traits. The prevalence of SA was higher in MDD than in BPD patients. The risk of SA was elevated in MDD patients with a higher quintile of PRS in neuroticism and a lower quintile of PRS in extraversion. The multiple regression analysis results demonstrated that later age of onset, higher family support and resilience, and lower overall social support were protective factors against SA. From the perspective of suicide prevention efforts, strengthening family support and conducting resilience training for patients with mood disorders may be beneficial interventions in clinical settings.
Obesity has been associated with cognition in observational studies; however, whether its effect is confounding or a reverse causality remains inconclusive. This study aimed to investigate the causal ...relationships of overall obesity, measured by body mass index (BMI), and abdominal adiposity, measured by waist-hip ratio adjusted for BMI (WHRadjBMI), and cognition across European and Asian populations using Mendelian randomization (MR) analysis.
We used publicly available genome-wide association study (GWAS) summary data of European ancestry, including BMI (n = 322,154) and WHRadjBMI (n = 210,088) from the GIANT consortium, and cognition performance (n = 257,828) from the UK Biobank and COGENT consortium. Data for individuals of Asian ancestry were retrieved from Taiwan Biobank to perform GWAS for BMI (n = 65,689), WHRadjBMI (n = 65,683), and Mini-Mental State Examination (MMSE, n = 21,273). MR analysis was carried out using the inverse-variance weighted method for the main results. Further, we examined the overall pleiotropy by MR-Egger intercept, and detected and adjusted for possible outliers using MR PRESSO.
No causal effect of BMI on cognition performance (beta 95% CI = 0.00 -0.07, 0.07, p value = 0.91) was found for Europeans; however, a 1-SD increase in WHRadjBMI was associated with a 0.07 standardized score decrease in cognition performance (beta 95% CI = -0.07 -0.12, -0.02, p value = 0.006). Further, no causal effect of BMI on MMSE (beta 95% CI = 0.01 -0.08, 0.10, p = 0.91) was found for Asians; however, a 1-SD increase in WHRadjBMI was associated with a 0.17 standardized score decrease in MMSE (beta 95% CI = -0.17 -0.30, -0.03, p = 0.02). In both populations, overall pleiotropy was not detected, and outliers did not affect the robustness of the main findings.
This trans-ethnic MR study reveals that abdominal adiposity, as measured by WHR adjusted for BMI, impairs cognition, whereas weak evidence suggests that BMI impairs cognition.
Suicide is a major threat to adolescent health. Sleep problems increase the risk of adolescent suicidal behavior, but the role of sleep-disordered breathing (e.g., sleep apnea) is unclear. We ...investigated whether sleep apnea had an effect on suicidal ideation that was independent of depression and perceived stress. We examined a series of sleep variables with suicidal ideation in 746 fifth and seventh graders using self-reported questionnaires to assess time in bed, sleep quality, insomnia, and sleep apnea while controlling depression and perceived stress. Overall, 8.8% of students aged 10–14 years reported having recent suicidal ideation, and 33% or 3.8%, depending on the screening criteria, reported having suspected sleep apnea. The sleep variables were all associated with an increased risk of suicidal ideation, but the magnitude of effects was largely attenuated when depression and perceived stress were included in the models. Suspected sleep apnea using daytime sleepiness as a screening criterion was independently associated with suicidal ideation (odds ratio = 2.25,
p
< 0.05). Suspected sleep apnea was associated with suicidal ideation that was partly independent of depression and stress, which reveals the pertinence of screening for sleep apnea among school students and designing proper prevention strategies for reducing youth suicidal behavior.
Iron is an essential micronutrient for the brain development of the fetus. Altered intestinal microbiota might affect behavior and cognition through the so-called microbiota-gut-brain axis. We used a ...Sprague-Dawley rat model of a maternal low-iron diet to explore the changes in cognition, dorsal hippocampal brain-derived neurotrophic factor (BDNF) and related pathways, gut microbiota, and related metabolites in adult male offspring. We established maternal iron-deficient rats by feeding them a low-iron diet (2.9 mg/kg), while the control rats were fed a standard diet (52.3 mg/kg). We used a Morris water maze test to assess spatial learning and long-term memory. Western blot (WB) assays and a quantitative reverse-transcription polymerase chain reaction (qRT-PCR) were used to detect the BDNF concentration and related signaling pathways. We collected fecal samples for microbiota profiling and measured the concentrations of plasma short-chain fatty acids. The adult male offspring of maternal rats fed low-iron diets before pregnancy, during pregnancy and throughout the lactation period had (1) spatial deficits, (2) a decreased BDNF mRNA expression and protein concentrations, accompanied by a decreased TrkB protein abundance, (3) a decreased plasma acetate concentration, and (4) an enrichment of the
genus
and
genus
. Maternal iron deficiency leads to an offspring spatial deficit and is associated with alternations in gastrointestinal microbiota and metabolites.
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