Treatment with paraquat affects the expression of ferroptosis-related genes.

OBJECTIVE: We aimed to explore the mechanisms underlying paraquat (PQ)-induced damage using cell lines (NCTC1469, TC-1, TCMK-1) and bioinformatic analysis of the GSE153959 dataset. Assessment of changes in the expression of ferroptosis-related genes in cellular damage due to paraquat poisoning and the important value of these genes in the pathogenesis. METHODS: Data were retrieved from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) related to ferroptosis were identified by Venn plots and analyzed for enrichment. Proteins encoded by these DEGs were studied for interactions. qRT-PCR and western blotting analyses of cultured cells were used to determine the expression of ferroptosis-related DEGs and their corresponding protein levels. RESULTS: We identified 25 DEGs primarily involved in epidermal growth factor receptor signaling, apoptotic signaling pathways, endoplasmic reticulum (ER) stress, and ferroptosis. From these, we uncovered eight ferroptosis-related DEGs, four of which were involved in ER response and regulators of ferroptosis-Chac1 (ChaC glutathione specific gamma-glutamylcyclotransferase 1), Atf3 (activating transcription factor 3), Tfrc (transferrin receptor), and Slc7a11 (solute carrier family 7 member 11). Significant changes in mRNA and protein levels of CHAC1, ATF3, TFRC, and SLC7A11 were confirmed in PQ-exposed cells. CONCLUSION: ER stress and ferroptosis are critical for PQ-induced cell damage. CHAC1, ATF3, TFRC, and SLC7A11 are essential molecules implicated in PQ-induced ferroptosis that may serve as therapeutic targets for the amelioration of PQ poisoning.

Evaluation of Void Defects behind Tunnel Lining through GPR forward Simulation.

Voids, a common defect in tunnel construction, lead to the deterioration of the lining structure and reduce the safety of tunnels. In this study, ground-penetrating radar (GPR) was used in tunnel lining void detection. Based on the finite difference time domain (FDTD) method, a forward model was established to simulate the process of tunnel lining void detection. The area of the forward image and the actual void area was analyzed based on the binarization method. Both the plain concrete and reinforced concrete lining with various sizes of air-filled and water-filled voids were considered. The rationality of the model was verified by measured data. It was observed that the response mode of voids can be hyperbolic, bowl-shaped, and strip-shaped, and this depends on the void's width. Compared with the air-filled voids, water filling increases the response range of the voids and produces a virtual image. Although the diffracted wave caused by a steel bar will bring about significant interference to the void response, the center position of the voids can be accurately located using 3D GPR.

Exogenous melatonin alleviates hemorrhagic shock­induced hepatic ischemic injury in rats by inhibiting the NF­κB/IκBα signaling pathway.

Melatonin (MT) is an indoleamine hormone that can counteract ischemia­induced organ injury through its antioxidant effects. The aim of the present study was to investigate the protective effects of exogenous MT against hemorrhagic shock (HS)­induced hepatic ischemic injury in rats, and the role of the nuclear factor (NF)­κB signaling pathway in this process. A rat model of HS­induced hepatic ischemic injury was established. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH), tumor necrosis factor (TNF)­α, interferon (IFN)­Î³, interleukin (IL)­6 and IL­1ß were measured every 6 h, and the 24­h survival rate of the rats was analyzed. All surviving rats were sacrificed after 24 h. Pathological changes in the liver and the hepatocyte apoptosis rate were observed by hematoxylin and eosin staining and TUNEL assay, respectively, and the expression levels of NF­κB p65 and NF­κB inhibitor α (IκBα) were analyzed by reverse transcription­quantitative PCR analysis and western blotting. The results demonstrated that the serum levels of ALT, AST, LDH, GDH, TNF­α, IFN­Î³, IL­6 and IL­1ß gradually increased after HS compared with those in rats subjected to a sham procedure, but this increase was attenuated by MT. Furthermore, the survival rate of the MT group was significantly higher compared with that of the HS group. The degree of pathological hepatic injury, the hepatocyte apoptosis rate, and the hepatic levels of TNF­α, IFN­Î³, IL­6 and IL­1ß were significantly decreased in the MT group compared with the HS group. In addition, the mRNA expression of NF­κB p65 was significantly decreased and the mRNA expression of IκBα was significantly increased in the MT group compared with the sham group. Furthermore, the NF­κB p65 protein levels in the MT group were significantly increased in the cytosol but decreased in the nucleus, and the IκBα protein levels were increased while those of phosphorylated IκBα were decreased compared with those in the HS group. Therefore, it may be inferred that exogenous MT alleviates HS­induced hepatic ischemic injury in rats via the inhibition of NF­κB activation and IκBα phosphorylation.

Bisexual Fertile Triploid Zebrafish (Danio rerio): a Rare Case.

Previous studies have suggested that artificially induced triploid zebrafish are exclusively male-biased. Owing to greatly inhibited gonadal development for the artificially induced triploid fish, they are regarded to be sterile in general. In this article, partially fertile bisexual triploid zebrafish are produced by suppressing extrusion of the second polar body by heat shock. Histological observation confirms that the early gonadal development of these triploid zebrafish is normal. Backcrossing and self-crossing are used to demonstrate that both the female and male triploid zebrafish have partial reproductive ability. Their dynamic of chromosomes during meiosis is revealed from the chromosome preparations of gonads. Examination of the expressed gonadal development-related genes shows some molecular evidence of the normal gonadal development in the triploid zebrafish. Clearly, these fertile bisexual triploid zebrafish can provide a unique system to study sex determination, as well as aneuploidy associated human diseases such as infertility and pregnancy loss.

Effect of hydrocortisone on the 28-day mortality of patients with septic acute kidney injury.

Objectives: To evaluate the efficacy of hydrocortisone in patients with septic acute kidney injury (SAKI).Methods: This retrospective cohort study consisted of all consecutive patients with SAKI who were admitted to the Taizhou First People's Hospital from March 2016 to February 2018. The patients who were treated with usual care including antibiotics, fluid resuscitation, and blood glucose control were regarded as the control group, and those received add-on hydrocortisone by the clinicians' discretion was considered in the intervention group. Hydrocortisone was administered as a 50 mg intravenous bolus every six hours for seven days. To adjust the potential baseline differences between the hydrocortisone and control groups, a 1:1 propensity score matching (PSM) was performed to identify a matched control subject for each patient in the hydrocortisone group.Results: In the propensity-matched cohort, the 28-day mortality was significantly lower for patients in the hydrocortisone group (p = .04). Both Acute Physiology and Chronic Health Evaluation (APACHE) II and the Sequential Organ Failure Assessment (SOFA) scores were significantly lower at day 7 in the hydrocortisone group (both p < .01). Serum IL-1ß, IL-6, and TNF-α concentrations significantly decreased for hydrocortisone group at day 7 (all p < .01). The levels of serum creatinine (SCr), Cystatin C (CysC), and procalcitonin (PCT) were significantly lower, while the levels of glomerular filtration rate (GFR) and urine volume were significantly higher for hydrocortisone group at day 7 (all p < .01).Conclusions: Glucocorticoid supplementation may improve renal function and reduce the 28-day mortality of patients with SAKI.

Multifunctional nanocomposites of superparamagnetic (Fe3O4) and NIR-responsive rare earth-doped up-conversion fluorescent (NaYF4 : Yb,Er) nanoparticles and their applications in biolabeling and fluorescent imaging of cancer cells.

A new kind of magnetic/luminescent multifunctional nanoparticles was synthesized by covalently linking multiple carboxyl-functionalized superparamagnetic Fe(3)O(4) nanoparticles and individual amino-functionalized silica-coated fluorescent NaYF(4) : Yb,Er up-conversion nanoparticles (UCNPs). The resultant nanocomposites bear active carboxylic and amino groups on the surface that were proved to be chemically active and useful for further facile bioconjugation with biomolecules. The UCNPs in the nanocomposite particles can emit visible light in response to the irradiation by near infrared (NIR) light, enabling the application of the nanocomposites in bioimaging. X-Ray diffraction, infrared spectroscopy, transmission electron microscopy, luminescence spectroscopy, and magnetometry were applied to characterize the multifunctional nanocomposites. The nanocomposites exhibited good superparamagnetic and excellent green up-conversion photoluminescent properties that can be exploited in magnetic separation and guiding as well as bioimaging. Due to the presence of active functional groups on the nanocomposite surface, the Fe(3)O(4)/NaYF(4) : Yb,Er magnetic/luminescent nanocomposites were successfully conjugated with a protein called transferrin, which specifically recognizes the transferrin receptors overexpressed on HeLa cells, and can be employed for biolabeling and fluorescent imaging of HeLa cells. Because NIR light can penetrate biological samples with good depth without damaging them and can avoid autofluorescence from them, the presence of both NIR-responsive UCNPs and superparamagnetic nanoparticles in the nanocomposite particles will enable the practical application of the nanocomposites in bioimaging and separation.