Hypoxia-mediated attenuation of EGLN2 inhibition of the NF-κB signaling pathway leads to the formation of a loop between HIF-1α and MUC1-C promoting chemoresistance in bladder cancer.

The expression pattern of MUC1-C in tumors is closely linked to tumor progression; however, its specific mechanism remains unclear. The expression of MUC1-C in cancer and adjacent normal tissues was detected using immunohistochemistry and Western blot. The IC50 of cells to gemcitabine was determined using the CCK8 assay. The effects of hypoxia and MUC1-C on the behavioral and metabolic characteristics of bladder cancer cells were investigated. Gene expression was assessed through Western blot and polymerase chain reaction. The relationship between the genes was analyzed by co-immunoprecipitation, immunofluorescence and Western blot. Finally, the role of the EGLN2 and NF-κB signaling pathways in the interaction between MUC1-C and hypoxia-inducible factor-1α (HIF-1α) was investigated. MUC1-C expression is significantly higher in bladder cancer tissues than in adjacent normal tissues, particularly in large-volume tumors, and is closely correlated with clinical features such as tumor grade. Tumor volume-mediated hypoxia resulted in increased expression of MUC1-C and HIF-1α in bladder cancer cells. Under stimulation of hypoxia, the inhibitory effect of EGLN2 on the NF-κB signaling pathway was weakened, allowing NF-κB to promote the positive feedback formation of MUC1-C and HIF-1α. Simultaneously, EGLN2-mediated degradation of HIF-1α was reduced. This ultimately led to elevated HIF-1α-mediated downstream gene expression, promoting increased glucose uptake and glycolysis, and ultimately resulting in heightened chemotherapy resistance and malignancy.

Synthesis of 4-trifluoromethyl pyridazines via annulation of pyridinium ylides with trifluoroacetyl diazoester.

A base promoted annulation of pyridinium ylides with trifluoroacetyl diazoester has been reported. Highly functionalized 4-trifluoromethyl pyridazines were synthesized in good yields without the use of any heavy metal catalysts. The developed methodology was compatible with a variety of important functional groups. Mechanistic studies revealed that trifluoroacetylated hydrazone was an active intermediate of this three-component annulation. Synthetic versatility of the method via aminolysis and condensation toward amide- and pyridazino[4,5-c]pyridazine-derivatives has been showcased.

Isolation of a degrading strain of Fusarium verticillioides and bioremediation of glyphosate residue.

Glyphosate is a broad-spectrum and nonselective organophosphorus herbicide that inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), an enzyme in the shikimate pathway in plants. A glyphosate-resistant fungus identified as Fusarium verticillioides was screened from soil subjected to long-term glyphosate application, and this fungus could grow in inorganic salt medium containing 90 mmol/L glyphosate. The optimum culture conditions identified via the response surface curve method were 28 °C and pH 7.0. The target gene epsps was cloned in this study, and the open reading frame contained 1170 nucleotides and putatively encoded 389 amino acid residues. Phylogenetic analysis showed that this gene belonged to class I, genes naturally sensitive to glyphosate. q-PCR confirmed that the relative expression level of the epsps gene was low, and no significant difference in expression was observed among different glyphosate concentrations at 12 h or 48 h. On day 28, the degradation by Fusarium verticillioides C-2 of sterilized soil and unsterilized soil supplemented with 60 mg/kg glyphosate reached 72.17% and 89.07%, respectively, and a significant difference was observed between the treatments with and without the glyphosate-degrading strain. The recovery of soil dehydrogenase activity after the addition of Fusarium verticillioides was significantly higher than that in the absence of the degrading fungus on the 28th day. The results showed that C-2 is a highly effective glyphosate-degrading strain with bioremediation potential for glyphosate-contaminated soil.

[Survey on intestinal nematode infections among school students in Tengchong County].

One primary school and one middle school were selected from Gudong Town, Tengyue Town and Puchuan Township of Tengchong County, respectively, by using the lamination stochastic group sampling method. The intestinal parasite infections were investigated with the iodine-stained direct smear method and modified Kato-Katz thick smears method. A total of 1 134 students were investigated and the total infection rate of intestinal nematodes was 12.4% (141/1 134). The infection rate of Ascaris lumbricoides, Trichuris trichura, and hookworm was 9.4% (106/1 134), 2.8% (32/1 134), and 0.3% (3/1 134), respectively. The prevalence of intestinal nematodes among the students of urban (2.2%, 8/363) was lower than those of rural (17.3%, 133/771) (P < 0.01). The infection rate in students from Gudong Town was higher than those of Tengyue (2.2%, 8/363) and Puchuan County (2.3%, 8/35) (P < 0.01), whereas the economy level of Gudong Town (29.9%, 123/412) was the best in the three towns. After all, the infection rate of the middle school students (13.7%, 59/432) was higher than that of pupils (11.7%, 82/702) (P < 0.01). Compared with 2003, the prevalence of nematode infection among the school students in Tengchong County decreased significantly in 2013.

Satellite record reveals 1960s acceleration of Totten Ice Shelf in East Antarctica.

Wilkes Land and Totten Glacier (TG) in East Antarctica (EA) have been losing ice mass significantly since 1989. There is a lack of knowledge of long-term mass balance in the region which hinders the estimation of its contribution to global sea level rise. Here we show that this acceleration trend in TG has occurred since the 1960s. We reconstruct ice flow velocity fields of 1963-1989 in TG from the first-generation satellite images of ARGON and Landsat-1&4, and build a five decade-long record of ice dynamics. We find a persistent long-term ice discharge rate of 68 ± 1 Gt/y and an acceleration of 0.17 ± 0.02 Gt/y2 from 1963 to 2018, making TG the greatest contributor to global sea level rise in EA. We attribute the long-term acceleration near grounding line from 1963 to 2018 to basal melting likely induced by warm modified Circumpolar Deep Water. The speed up in shelf front during 1973-1989 was caused by a large calving front retreat. As the current trend continues, intensified monitoring in the TG region is recommended in the next decades.

Helicobacter pylori and unignorable extragastric diseases: Mechanism and implications.

Considered as the most popular pathogen worldwide, Helicobacter pylori is intensively associated with diverse gastric diseases, including gastric ulcers, chronic progressive gastritis, and gastric cancer. Aside from its pathogenic effect on gastric diseases, growing evidences reveal that H. pylori may be related to numerous extragastric diseases. In this article, we reviewed recent studies and systematically elucidated that H. pylori may interfere with many biological processes outside the stomach and influence the occurrence of various extragastric diseases. Many epidemiological studies have indicated that H. pylori plays a pathogenic role in COVID-19, atherosclerosis, hyperemesis gravidarum and several other extragastric diseases, while the effect of H. pylori is currently under investigation in gastroesophageal reflux disease, asthma, and inflammatory bowel disease. Moreover, we also summarized the possible pathogenic mechanisms of H. pylori that may be related to chronic systemic inflammation and molecular mimicker. Taken together, this review provides a new perspective on the role of H. pylori in extragastric diseases and explores the possible mechanisms, which may help guide clinical treatment.

Instrument-free quantitative gold nanoparticle-based liquid-phase colorimetric assays for use in resource-poor environments.

This work describes a new class of gold nanoparticle-based liquid-phase colorimetric assay (GNP-LPCA) termed as two dimensional (2D) GNP-LPCA. Its utility is demonstrated with the development of an aptamer-based 2D GNP-LPCA for simple, low-cost, sensitive, specific, and quantitative detection of adenosine as a model analyte in buffer and human serum samples with the naked eye.