Chronic CSE Treatment Induces the Growth of Normal Oral Keratinocytes via PDK2 Upregulation, Increased Glycolysis and HIF1α Stabilization

Exposure to cigarette smoke is a major risk factor for head and neck squamous cell carcinoma (HNSCC). We have previously established a chronic cigarette smoke extract (CSE)-treated human oral normal keratinocyte model, demonstrating an elevated frequency of mitochondrial mutations in CSE treated cells. Using this model we further characterized the mechanism by which chronic CSE treatment induces increased cellular proliferation.We demonstrate that chronic CSE treatment upregulates PDK2 expression, decreases PDH activity and thereby increases the glycolytic metabolites pyruvate and lactate. We also found that the chronic CSE treatment enhanced HIF1α accumulation through increased pyruvate and lactate production in a manner selectively reversible by ascorbate. Use of a HIF1α small molecule inhibitor blocked the growth induced by chronic CSE treatment in OKF6 cells. Furthermore, chronic CSE treatment was found to increase ROS (reactive oxygen species) production, and application of the ROS scavengers N-acetylcysteine abrogated the expression of PDK2 and HIF1α. Notably, treatment with dichloroacetate, a PDK2 inhibitor, also decreased the HIF1α expression as well as cell proliferation in chronic CSE treated OKF6 cells.Our findings suggest that chronic CSE treatment contribute to cell growth via increased ROS production through mitochondrial mutations, upregulation of PDK2, attenuating PDH activity thereby increasing glycolytic metabolites, resulting in HIF1α stabilization. This study suggests a role for chronic tobacco exposure in the development of aerobic glycolysis and normoxic HIFα activation as a part of HNSCC initiation. These data may provide insights into development of chemopreventive strategies for smoking related cancers

Microbiota comparison of amur ide (Leuciscus waleckii) intestine and waters at alkaline water and freshwater as the living environment

The intestinal microbiota of marine animals was influenced by the water and environment in which they live. The Amur ide (Leuciscus waleckii) adapts to extremely high alkalinity and is an ideal material for aquacultural studies of alkaline adaptation. In this study, we screened intestinal indicator flora and functional redundancy of intestinal colonies in alkaline-water species (AW) and freshwater species (FW) of Amur ide (L. waleckii) in these different aquatic environments. The available vs. community composition correlations were then predicted by contrasting each other with the flora contained in environmental water samples. Here, five microbial species and six genera were identified owing to the classifiable sequence. The intestinal microbiota that existed in AW and FW had approximately 1/3 of the operational taxonomic units in the respective living water environments, meaning gut microbes in the aqueous habitats will have an influential association with gut microbes in AW and FW. Compared to the bacterial composition of the FW intestine and that present in freshwater, Moraxella osloensis, Psychrobacter maritimus, and Psychrobacter faecalis were significantly enriched in the intestine of AW and alkaline water samples. In the FW intestine and freshwater samples, however, Cryptomonas curvata and Polynucleobacter asymbioticus were highly improved, which can be summarized as Enterobacter sp., the predominant population in the AW gut, while Aeromonas and Ralstonia being primarily present in FW intestines. Photosynthetic bacteria were most significant in both water samples. The results indicated that the intestinal microbiota composition, abundance, and diversity of AW and FW were quite different. In contrast, the microbial composition of the additional alkaline water and freshwater environments showed slight differences. This study expects to enhance our understanding of the alkalinity tolerance of L. waleckii, which will be provided for the breeding of fish living in alkaline water, and push the development of alkaline water resources with increased efficiency.info:eu-repo/semantics/publishedVersio

Acute resource pulses from periodical cicadas propagate to belowground food webs but do not affect tree performance

Acute resource pulses can have dramatic legacies for organismal growth, but the legacy effects of resource pulses on broader aspects of community structure and ecosystem processes are less understood. Mass emergence of periodical cicadas (Magicicada spp.) provides an excellent opportunity to shed light on the influence of resource pulses on community and ecosystem dynamics: the adults emerge every 13 or 17 years in vast numbers over much of eastern North America, with a smaller but still significant number becoming incorporated into forest food webs. To study the potential effects of such arthropod resource pulse on primary production and belowground food webs, we added adult cicada bodies to the soil surface surrounding sycamore trees and assessed soil carbon and nitrogen concentrations, plant-available nutrients, abundance and community composition of soil fauna occupying various trophic levels, decomposition rate of plant litter after 50 and 100 days, and tree performance for 4 years. Contrary to previous studies, we did not find significant cicada effects on tree performance despite observing higher plant-available nutrient levels on cicada addition plots. Cicada addition did change the community composition of soil nematodes and increased the abundance of bacterial- and fungal-feeding nematodes, while plant feeders, omnivores, and predators were not influenced. Altogether, acute resource pulses from decomposing cicadas propagated belowground to soil microbial-feeding invertebrates and stimulated nutrient mineralization in the soil, but these effects did not transfer up to affect tree performance. We conclude that, despite their influence on soil food web and processes they carry out, even massive resource pulses from arthropods do not necessarily translate to NPP, supporting the view that ephemeral nutrient pulses can be attenuated relatively quickly despite being relatively large in magnitude.Peer reviewe

Analysis of factors influencing the efficacy of vagus nerve stimulation for the treatment of drug-resistant epilepsy in children and prediction model for efficacy evaluation

ObjectiveVagus nerve stimulation (VNS) has been widely used in the treatment of drug-resistant epilepsy (DRE) in children. We aimed to explore the efficacy and safety of VNS, focusing on factors that can influence the efficacy of VNS, and construct a prediction model for the efficacy of VNS in the treatment of DRE children.MethodsRetrospectively analyzed 45 DRE children who underwent VNS at Qilu Hospital of Shandong University from June 2016 to November 2022. A ≥50% reduction in seizure frequency was defined as responder, logistic regression analyses were performed to analyze factors affecting the efficacy of VNS, and a predictive model was constructed. The predictive model was evaluated by receiver operating characteristic curve (ROC), calibration curves, and decision curve analyses (DCA).ResultsA total of 45 DRE children were included in this study, and the frequency of seizures was significantly reduced after VNS treatment, with 25 responders (55.6%), of whom 6 (13.3%) achieved seizure freedom. There was a significant improvement in the Quality of Life in Childhood Epilepsy Questionnaire (15.5%) and Seizure Severity Score (46.2%). 16 potential factors affecting the efficacy of VNS were included, and three statistically significant positive predictors were ultimately screened: shorter seizure duration, focal seizure, and absence of intellectual disability. We developed a nomogram for predicting the efficacy of VNS in the treatment of DRE children. The ROC curve confirmed that the predictive model has good diagnostic performance (AUC = 0.864, P < 0.05), and the nomogram can be further validated by bootstrapping for 1,000 repetitions, with a C-index of 0.837. Besides, this model showed good fitting and calibration and positive net benefits in decision curve analysis.ConclusionVNS is a safe and effective treatment for DRE children. We developed a predictive nomogram for the efficacy of VNS, which provides a basis for more accurate selection of VNS patients

One-pot aqueous synthesis of sub-10 nm responsive nanogels

NSFC [21274118, 91227120, 20923004]; FRFCU [2012121016]; NFFTBS [J1030415]A strategy involving free radical copolymerization of a difunctional oligomer and a small-molecule crosslinker to give sub-10 nm nanogels is proposed. These nanogels can adapt to surrounding temperatures and regulate the release of a preloaded model anticancer drug 5-fluorouracil

A genetic study of the NOS3 gene for ischemic stroke in a Chinese population

We recruited 560 unrelated patients with ischemic stroke and 153 unrelated controls to undertake a genetic analysis for association between the NOS3 gene and ischemic stroke. All the subjects were Chinese of Han descent. Because the NOS3 gene spans about 21 kb of DNA and contains 26 exons, we selected a single nucleotide polymorphism (SNP) rs3918181, an A to G base change located in intron 14 of the gene, as a DNA marker. PCR-based restriction fragment length polymorphism analysis was applied to genotype rs3918181 (RsaI site). The chi-square (χ2) goodness-of-fit test showed that the genotypic distributions of the marker were not deviated from Hardy-Weinberg equilibrium in both the patient group (χ2 = 0.166, p = 0.684) and the control group (χ2 = 0.421, p = 0.517). The cocaphase analysis showed allelic association of rs3918181 with ischemic stroke in males (χ2 = 4.04, p = 0.044, OR = 1.43, 95% CI 1.01∼2.02) and frequency of allele A was significantly higher in male patients than male control subjects. The χ2 test revealed genotypic association between rs3918181 and ischemic stroke in males (χ2 = 4.26, df = 1, p = 0.039, OR = 1.61, 95% CI 1.02∼2.53) but not in females. The present work suggests that rs3918181 is associated with ischemic stroke in male patients. This finding gives further evidence in support of the eNOS association with ischemic stroke in the Chinese population

Intraspecific aggression in the jewel cichlid Hemichromis bimaculatus reared under different background colours

The jewel cichlid Hemichromis bimaculatus is a popular freshwater ornamental fish with high market demand. However, it is aggressive and difficult to be maintained in captivity. Background colours are known to influence fish aggression, but there is still no such information available on H. bimaculatus. This study was conducted to examine the influence of 6 background colours (black, white, blue, yellow, green or red) on the aggression (chasing frequency), survival, weight gain and feed intake of the H. bimaculatus, through a 60-day culture trial. At the end of this trial, since the total feed intake and fish weight gain (except black) were similar among all treatments, the green was the most recommended background colour for the H. bimaculatus culture as it has the highest fish survival, followed by the white and yellow. Low fish survival was found under the black, red and blue; hence, these background colours were not recommended. In this study, we suspected that different background colours may induce different aggressiveness degree in the H. bimaculatus, and biting may have occurred to cause low fish survival. Also, the blue was speculated to be a stressful background colour to the H. bimaculatus. Nevertheless, further study is necessary to elucidate these hypotheses

Optimism/pessimism and health-related quality of life during pregnancy across three continents: a matched cohort study in China, Ghana, and the United States

<p>Abstract</p> <p>Background</p> <p>Little is known about how optimism/pessimism and health-related quality of life compare across cultures.</p> <p>Methods</p> <p>Three samples of pregnant women in their final trimester were recruited from China, Ghana, and the United States (U.S.). Participants completed a survey that included the Life Orientation Test - Revised (LOT-R, an optimism/pessimism measure), the Short Form 12 (SF-12, a quality of life measure), and questions addressing health and demographic factors. A three-country set was created for analysis by matching women on age, gestational age at enrollment, and number of previous pregnancies. Anovas with post-hoc pairwise comparisons were used to compare results across the cohorts. Multivariate regression analysis was used to create a model to identify those variables most strongly associated with optimism/pessimism.</p> <p>Results</p> <p>LOT-R scores varied significantly across cultures in these samples, with Ghanaian pregnant women being the most optimistic and least pessimistic and Chinese pregnant women being the least optimistic overall and the least pessimistic in subscale analysis. Four key variables predicted approximately 20% of the variance in overall optimism scores: country of origin (p = .006), working for money (p = .05); level of education (p = .002), and ever being treated for emotional issues with medication (p < .001). Quality of life scores also varied by country in these samples, with the most pronounced difference occurring in the vitality measure. U.S. pregnant women reported far lower vitality scores than both Chinese and Ghanaian pregnant women in our sample.</p> <p>Conclusion</p> <p>This research raises important questions regarding what it is about country of origin that so strongly influences optimism/pessimism among pregnant women. Further research is warranted exploring underlying conceptualization of optimism/pessimism and health related quality of life across countries.</p

Molecular Analysis of Virulent Determinants of Enterovirus 71

Enterovirus 71 (EV71) is the most important causative agent of hand, foot and mouth disease (HFMD) in children. In most cases, it is a self-limiting illness. However some EV71 infectious cases can develop severe clinical outcomes, such as encephalitis, meningitis, poliomyelitis like paralysis, and even death. To identify the determinants of virulence, the deduced amino acid sequence of polyprotein and nucleotide sequence of 5′-NTR and 3′-NTR in 25 SC-EV71 strains (strains from severe cases) and 31 MC-EV71 strains (strains from mild cases) were analyzed. Results showed four amino acids on two positions (GlyP710/GlnP710/ArgP710 and GluP729) on the DE and EF loop of VP1, one (LysP930) on the surface of protease 2A and four nucleotides on three positions (GP272, UP488 and AP700/UP700) in the 5'-NTR region are associated with EV71 virulent phenotype. Predicted secondary structure of RNA using the consensus sequence of 5'-NTR by RNAStructure showed the mutation of nucleotide at position 488 in strain BJ08-Z004-3 (position 491 in prototype strain BrCr) can result in the discrepancy of an additional pair of nucleotides and thus change the stability of the second structure of IRES. Fragment base content analysis showed that in the region 696 to 714 bp at the 5'-NTR, where the AP700/UP700 was located, the nucleotide constitution ratios differed significantly between SC-EV71 and MC-EV71 strains. In conclusion, comparative genomic analysis showed that virulence of EV71 strains are mainly determined by the amino acids on two positions of VP1, one position of protease 2A and the nucleotides on three positions in 5'-NTR

Vitamin E stabilizes iron and mitochondrial metabolism in pulmonary fibrosis

Introduction: Pulmonary fibrosis (PF) is a fatal chronic lung disease that causes structural damage and decreased lung function and has a poor prognosis. Currently, there is no medicine that can truly cure PF. Vitamin E (VE) is a group of natural antioxidants with anticancer and antimutagenic properties. There have been a few reports about the attenuation of PF by VE in experimental animals, but the molecular mechanisms are not fully understood.Methods: Bleomycin-induced PF (BLM-PF) mouse model, and cultured mouse primary lung fibroblasts and MLE 12 cells were utilized. Pathological examination of lung sections, immunoblotting, immunofluorescent staining, and real-time PCR were conducted in this study.Results: We confirmed that VE significantly delayed the progression of BLM-PF and increased the survival rates of experimental mice with PF. VE suppressed the pathological activation and fibrotic differentiation of lung fibroblasts and epithelial-mesenchymal transition and alleviated the inflammatory response in BLM-induced fibrotic lungs and pulmonary epithelial cells in vitro. Importantly, VE reduced BLM-induced ferritin expression in fibrotic lungs, whereas VE did not exhibit iron chelation properties in fibroblasts or epithelial cells in vitro. Furthermore, VE protected against mitochondrial dysmorphology and normalized mitochondrial protein expression in BLM-PF lungs. Consistently, VE suppressed apoptosis in BLM-PF lungs and pulmonary epithelial cells in vitro.Discussion: Collectively, VE markedly inhibited BLM-induced PF through a complex mechanism, including improving iron metabolism and mitochondrial structure and function, mitigating inflammation, and decreasing the fibrotic functions of fibroblasts and epithelial cells. Therefore, VE presents a highly potential therapeutic against PF due to its multiple protective effects with few side effects