Wettability between molten slag and dolomitic refractory

In the current study, the wettability between molten slag and dolomitic refractory materials used in the ladle during steel refining was investigated. The contact angle between molten slag and dolomitic substrate decreased with increasing temperature. The slag with lower basicity spread on the substrate more easily and penetrated deeper into the substrate. The penetration depth of slag into the refractory increased with the extension of holding time. The CaO in the refractory dissolved into slag which was then saturated with CaO. The reaction between slag and substrate resulted in the formation of solid Ca3SiO5, which slowed down the further penetration of slag into the refractory

Induction of cell cycle arrest via the p21, p27–cyclin E,A/Cdk2 pathway in SMMC-7721 hepatoma cells by clioquinol

Clioquinol has been shown to have anticancer activity in several carcinoma cells. In this study, we preliminarily examined the effect of clioquinol in human SMMC-7721 hepatoma and QSG-7701 normal hepatic cells. Our results indicated that clioquinol did not significantly affect survival of QSG-7701 cells, whereas it reduced cell viability in a concentration- and time-dependent manner in SMMC-7721 cells. Clioquinol did not trigger autophagy and apoptosis, while it induced cell cycle arrest in the S-phase in SMMC-7721 cells. Additionally, down-regulation of cyclin D1, A2, E1, Cdk2 and up-regulation of p21, p27 were detected after the treatment of clioquinol. The results demonstrated for the first time that clioquinol suppressed cell cycle progression in the S-phase in SMMC-7721 cells via the p21, p27–cyclin E,A/Cdk2 pathway. This suggests that clioquinol may have a therapeutic potential as an anticancer drug for certain malignances

Effect of neferine on diabetic nephropathy by regulating SDF-1/CXCR4 signal pathway

Objective·To investigate the effect of neferine (Nef) on renal tissues of diabetic nephropathy (DN) rats and its related mechanism.Methods·DN model rats were constructed by feeding high-fat diet combined with intraperitoneal injection of streptozotocin, and the successfully constructed rats were randomly divided into DN group, Nef (low, medium and high) dose groups and Nef high-dose+pathway antagonist (AMD3100) group, with 10 rats in each group. At the same time, 10 common rats were selected as the normal group. The levels of fasting blood glucose (FBG), 24 h urinary protein, serum glycosylated hemoglobin (HbA1c), serum creatinine (Scr), blood urea nitrogen (BUN) and renal index of rats in the six groups were measured. Hematoxylin-eosin (H-E) and Masson staining were used to observe the pathological changes of renal tissues. The content of malondialdehyde (MDA) in renal tissues was determined by thiobarbituric acid (TBA) method, and the activities of superoxide dismutase (SOD) and catalase (CAT) in renal tissues were determined by water soluble tetrazolium (WST-1) method and ammonium molybdate method, respectively. The mRNA and protein expressions of stromal cell-derived factor-1 (SDF-1) and CXC chemokine receptor 4 (CXCR4) in renal tissues were detected by quantitative real-time PCR (qPCR) and Western blotting, respectively. Rat renal tubular epithelium cells NRK-52E were induced by high glucose (30 mmol/L glucose) to establish DN cell model. The cells were divided into control group, high glucose (HG) group, HG+Nef (low, medium and high) dose (i.e.HG+Nef-L, M and H) group, and HG+Nef-H +AMD3100 group. SOD and CAT activities were detected by WST-1 method and ammonium molybdate method, respectively. MDA content was detected by TBA method. The mRNA and protein expressions of SDF-1 and CXCR4 were detected by qPCR and Western blotting, respectively. CCK-8 method and flow cytometry were used to detect cell viability and apoptosis rate, respecti-vely.Results·Compared with the DN group, the levels of FBG, 24 h urinary protein, HbA1c, Scr, BUN, renal index and MDA content in Nef (low, medium and high) dose groups and Nef high-dose+AMD3100 group were decreased, the mRNA and protein expressions of SDF-1 and CXCR4 were increased, and the activities of SOD and CAT were increased (all P<0.05). The degree of pathological damage and fibrosis of renal tissues was reduced; all of the above changes were dose-dependent. AMD3100 could weaken the renal protective effect of high-dose Nef on DN rats. Compared with the HG group, NRK-52E cell viability, SOD and CAT activities, and the mRNA and protein expressions of SDF-1 and CXCR4 were increased in HG+Nef-L, M and H groups, while apoptosis rate and MDA content were decreased (all P<0.05). AMD3100 could reverse the protective effect of Nef-H on NRK-52E cell damage.Conclusion·Nef may control blood glucose levels on DN rats and improve antioxidant capacity by activating the SDF-1/CXCR4 signal pathway, playing a renal protective role

Acetylation-defective mutant of Pparγ is associated with decreased lipid synthesis in breast cancer cells.

In our prior publications we characterized a conserved acetylation motif (K(R)xxKK) of evolutionarily related nuclear receptors. Recent reports showed that peroxisome proliferator activated receptor gamma (PPARγ) deacetylation by SIRT1 is involved in delaying cellular senescence and maintaining the brown remodeling of white adipose tissue. However, it still remains unknown whether lysyl residues 154 and 155 (K154/155) of the conserved acetylation motif (RIHKK) in Pparγ1 are acetylated. Herein, we demonstrate that Pparγ1 is acetylated and regulated by both endogenous TSA-sensitive and NAD-dependent deacetylases. Acetylation of lysine 154 was identified by mass spectrometry (MS) while deacetylation of lysine 155 by SIRT1 was confirmed by in vitro deacetylation assay. An in vivo labeling assay revealed K154/K155 as bona fide acetylation sites. The conserved acetylation sites of Pparγ1 and the catalytic domain of SIRT1 are both required for the interaction between Pparγ1 and SIRT1. Sirt1 and Pparγ1 converge to govern lipid metabolism in vivo. Acetylation-defective mutants of Pparγ1 were associated with reduced lipid synthesis in ErbB2 overexpressing breast cancer cells. Together, these results suggest that the conserved lysyl residues K154/K155 of Pparγ1 are acetylated and play an important role in lipid synthesis in ErbB2-positive breast cancer cells

Patterns of antibiotic use, pathogens, and prediction of mortality in hospitalized neonates and young infants with sepsis: A global neonatal sepsis observational cohort study (NeoOBS)

BACKGROUND: There is limited data on antibiotic treatment in hospitalized neonates in low- and middle-income countries (LMICs). We aimed to describe patterns of antibiotic use, pathogens, and clinical outcomes, and to develop a severity score predicting mortality in neonatal sepsis to inform future clinical trial design. METHODS AND FINDINGS: Hospitalized infants <60 days with clinical sepsis were enrolled during 2018 to 2020 by 19 sites in 11 countries (mainly Asia and Africa). Prospective daily observational data was collected on clinical signs, supportive care, antibiotic treatment, microbiology, and 28-day mortality. Two prediction models were developed for (1) 28-day mortality from baseline variables (baseline NeoSep Severity Score); and (2) daily risk of death on IV antibiotics from daily updated assessments (NeoSep Recovery Score). Multivariable Cox regression models included a randomly selected 85% of infants, with 15% for validation. A total of 3,204 infants were enrolled, with median birth weight of 2,500 g (IQR 1,400 to 3,000) and postnatal age of 5 days (IQR 1 to 15). 206 different empiric antibiotic combinations were started in 3,141 infants, which were structured into 5 groups based on the World Health Organization (WHO) AWaRe classification. Approximately 25.9% (n = 814) of infants started WHO first line regimens (Group 1-Access) and 13.8% (n = 432) started WHO second-line cephalosporins (cefotaxime/ceftriaxone) (Group 2-"Low" Watch). The largest group (34.0%, n = 1,068) started a regimen providing partial extended-spectrum beta-lactamase (ESBL)/pseudomonal coverage (piperacillin-tazobactam, ceftazidime, or fluoroquinolone-based) (Group 3-"Medium" Watch), 18.0% (n = 566) started a carbapenem (Group 4-"High" Watch), and 1.8% (n = 57) a Reserve antibiotic (Group 5, largely colistin-based), and 728/2,880 (25.3%) of initial regimens in Groups 1 to 4 were escalated, mainly to carbapenems, usually for clinical deterioration (n = 480; 65.9%). A total of 564/3,195 infants (17.7%) were blood culture pathogen positive, of whom 62.9% (n = 355) had a gram-negative organism, predominantly Klebsiella pneumoniae (n = 132) or Acinetobacter spp. (n = 72). Both were commonly resistant to WHO-recommended regimens and to carbapenems in 43 (32.6%) and 50 (71.4%) of cases, respectively. MRSA accounted for 33 (61.1%) of 54 Staphylococcus aureus isolates. Overall, 350/3,204 infants died (11.3%; 95% CI 10.2% to 12.5%), 17.7% if blood cultures were positive for pathogens (95% CI 14.7% to 21.1%, n = 99/564). A baseline NeoSep Severity Score had a C-index of 0.76 (0.69 to 0.82) in the validation sample, with mortality of 1.6% (3/189; 95% CI: 0.5% to 4.6%), 11.0% (27/245; 7.7% to 15.6%), and 27.3% (12/44; 16.3% to 41.8%) in low (score 0 to 4), medium (5 to 8), and high (9 to 16) risk groups, respectively, with similar performance across subgroups. A related NeoSep Recovery Score had an area under the receiver operating curve for predicting death the next day between 0.8 and 0.9 over the first week. There was significant variation in outcomes between sites and external validation would strengthen score applicability. CONCLUSION: Antibiotic regimens used in neonatal sepsis commonly diverge from WHO guidelines, and trials of novel empiric regimens are urgently needed in the context of increasing antimicrobial resistance (AMR). The baseline NeoSep Severity Score identifies high mortality risk criteria for trial entry, while the NeoSep Recovery Score can help guide decisions on regimen change. NeoOBS data informed the NeoSep1 antibiotic trial (ISRCTN48721236), which aims to identify novel first- and second-line empiric antibiotic regimens for neonatal sepsis. TRIAL REGISTRATION: ClinicalTrials.gov, (NCT03721302)

Development and validation of prognostic nomographs for patients with cervical cancer: SEER-based Asian population study

Abstract To develop and validate a nomograph to predict the long-term survival probability of cervical cancer (CC) patients in Asia, Surveillance, Epidemiology, and End Results (SEER) were used to collect information about CC patients in Asia. The patient data were randomly sampled and divided into a training group and a validation group by 7:3. Least absolute shrinkage and selection operator (LASSO) regression was used to screen key indicators, and multivariate Cox regression model was used to establish a prognostic risk prediction model for CC patients. The receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were adopted to comprehensively evaluate the nomogram model. LASSO regression and multivariate Cox proportional hazards model analysis showed that age, American Joint Committee on Cancer (AJCC) Stage, AJCC T, tumor size, and surgery were independent risk factors for prognosis. The ROC curve results proved that the area under curve (AUC) values of the training group in 3 and 5 years were 0.837 and 0.818, The AUC values of the validation group in 3 and 5 years were 0.796 and 0.783. DCA showed that the 3- and 5-year overall survival (OS) nomograms had good clinical potential value. The nomogram model developed in this study can effectively predict the prognosis of Asian patients with CC, and the risk stratification system based on this nomogram prediction model has some clinical value for discriminating high-risk patients

Compact temperature sensor with highly germania-doped fiber-based Michelson interferometer

A compact temperature sensor with highly germania-doped fiber (Ge-fiber)-based Michelson interferometer (MI) is proposed and experimentally demonstrated. It is constructed by splicing a 1-mm-long, 75 mol.% GeO2-doped fiber to a single-mode fiber and fabricating a taper at the splicing point. The fiber taper improves mode conversion efficiency and thus increases the extinction ratio of the interference fringe. The free spectral range is only 18.9 nm owing to the much larger differential refractive index of the Ge-fiber than normal fibers. By monitoring wavelength shift of the reflection spectrum, temperature measurement within a wide range of 30°C-400°C is successfully achieved with sensitivity up to 100 pm/°C, which is much higher than normal fiber-based MI sensors owing to the higher thermo-optic coefficient of the Ge-fiber. The compact size and high sensitivity make the proposed sensor a highly potential candidate in point measurement of temperature