LY294002 induces differentiation and inhibits invasion of glioblastoma cells by targeting GSK-3β and MMP

Glioblastomas are the most common and devastating primary tumors of the central nervous system, with high proliferative capacity, aggressive invasion, and resistance to conventional therapies. Differentiation therapy has emerged as a promising candidate modality. Here we show that the traditional phosphatidylinositol 3 kinase (PI3K) inhibitor LY294002 is capable of inducing differentiation of C6 glioblastoma cells characterized by morphological changes to astrocytic phenotype, increase in differentiation marker protein glial fibrillary acidic pro-tein and inhibition of proliferation. Small interfering RNA against glycogen synthase kinase-3β (GSK-3β) suppresses the induced-differentiation and invasiveness in C6 cells. LY294002 also inhibits MMP-9 expression and invasion of C6 cells, assembling the role of metalloprotease (MMP) inhibitor AG3340. Taken together, these findings suggest differentiation-inducing and invasion-inhibitory effectiveness of LY294002 in glioblastomas, most likely involving inhibition of GSK-3β and MMP respectively

The association of triglycerides and total cholesterol concentrations with newly diagnosed diabetes in adults in China

Background: It has already been suggested that high abnormal blood lipid concentration is associated with hyperglycaemia. However, no data is available about the roles of triglycerides (TG) and total cholesterol (TC) levels in diabetes. Here, for the first time we investigated the roles of TG and TC levels, gender and abdominal fat in the development of newly diagnosed diabetes in China. Materials and Methods: Two population-based cross-sectional surveys were conducted from 2006 to 2009 in Qingdao, China. Newly diagnosed diabetes was defined according to FPG and/or 2 h PG criteria. The associations between diabetes and TG, and TC levels were assessed by multi-variable logistic regression models. Results: As compared with non-diabetes, the odds ratio[(95% confidence intervals), OR(95% CI)] for diabetes corresponding to hypertriglyceridemia (HTG) were 1.54 (1.01, 2.35) in men and 2.02 (1.49, 3.10) in women for TG and accompany with Hypercholesterolemia (HTC) 2.93 (1.97, 4.37) and 2.13 (1.49, 3.05) for TC, when both were fitted simultaneously in the model adjusting for age, geographic division, marital status, school years, family history of diabetes, monthly income, systolic blood pressure (SBP), diastolic blood pressure (DBP), waist circumference (WC), high density lipoprotein cholesterol (HDL-C), alanine amino transferase (ALT) and gamma-glutamyltransferase (GGT). Conclusions: HTG in both gender, borderline high TC and HTC in men were an independent risk factor for diabetes in this Chinese population, however, HTC was mediated through abdominal fat for diabetes in women. Our findings may help to enhance the current knowledge of diabetes patho-physiology, and the associations between TG, TC level and diabetes is also clinically informative.Peer reviewe

Correlation of DNA load, genotyping, and clinical phenotype of Mycoplasma pneumoniae infection in children

IntroductionThis study aimed to investigate the correlation between Mycoplasma pneumoniae (MP)-DNA load in the bronchoalveolar lavage fluid (BALF) of children with MP pneumonia (MPP) and its subtypes, relevant laboratory data, imaging, extrapulmonary complications in infected children, and its clinical significance in evaluating the disease.MethodsChildren hospitalized with MPP at Tianjin Children's Hospital between December 2017 and December 2020 were selected for the study, excluding those with mixed viral, bacterial, and fungal infections. Children were divided into low- and high-load groups according to the MP DNA load in BALF using real-time quantitative fluorescence polymerase chain reaction (PCR). After a successful MP culture, positive specimens were subjected to PCR-Restriction fragment length polymorphism and Multiple-locus variable number tandem repeat analysis typing. Basic data, clinical information, laboratory data, and radiological results were collected from all children included in the study.ResultsThe PI-I type dominated the different load groups. Children in the low-load group had more wheezing and shortness of breath; however, children in the high-load group had a higher length of hospitalization, maximum fever temperature, higher chills/chilliness, incidence of abdominal pain, and higher C-reactive protein (CRP), procalcitonin (PCT) and aspartate aminotransferase (AST) levels. Children in the high-load group were more likely to have imaging changes such as pleural effusion, and the incidence of respiratory infections and extrapulmonary complications was higher than that of those in the low-load group. We applied Spearman's correlation analysis to clarify the relationship between MP DNA load and the clinical severity of MPP. We found that MP DNA load was positively correlated with length of hospitalization, maximum fever temperature, CRP, PCT, Interleukin-6 (IL-6), and AST levels, and negatively correlated with fever and cough durations, white blood cell count (WBC), and proportion of monocytes (MONO). The degree of correlation was as follows: length of hospitalization > IL-6 > cough duration > AST > fever duration > PCT > WBC > proportion of MONO > maximum fever temperature > CRP levels.ConclusionsMP DNA load was not correlated with MP typing but was significantly correlated with the children's clinical phenotype. Therefore, the MP DNA load helps in the early diagnosis of infection and can better predict disease regression

Association Between Different Indicators of Obesity and Depression in Adults in Qingdao, China: A Cross-Sectional Study

Background: This study was designed to investigate the perceived relationship between body weight and depression risk in a Chinese population in Qingdao, China.Methods: A population-based cross-sectional survey was performed with 4,573 participants (between 35 and 74 years) from the year 2009 to 2012 in Qingdao, China. We applied the Zung self-rating depression scale to ascertain the level of depression in participants. The associations between different indicators of obesity [body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR)] and depression were assessed by logistic regression based on the Chinese criteria of obesity. Sensitivity analysis was done based on the Asian and WHO criteria of obesity.Results: The Zung scores for the 243 participants (5.2%) were over 45 and they were entitled as depression. Furthermore, multivariable logistic analyses revealed that being overweight [odds ratios (OR): 1.48, 95% confidence intervals [95% CI]: 1.08–2.03] and having abdominal obesity (WC category in Chinese criteria) (OR: 1.47, 95% CI: 1.08-2.00) were often associated with a higher risk for depression compared to normal weight subjects. Sensitivity analysis revealed that abdominal obesity (Asian criterion) (OR: 1.41, 95% CI: 1.03-1.91) was a significant risk factor for depression. Similarly, being overweight (WHO criterion) (OR: 1.39, 95% CI: 1.03-1.87) was an obvious risk factor for depression.Conclusion: Being overweight and having abdominal obesity (WC category) were found to be linked with a higher risk of depression. However, abdominal obesity (WHR category) was not associated with depression

Triglycerides and total cholesterol concentrations in association with IFG/IGT in Chinese adults in Qingdao, China

Background: To investigative the association of triglycerides (TG) and total cholesterol (TC) concentrations with impaired fasting glucose/impaired glucose tolerance (IFG/IGT) in Chinese adults. Methods: The population-based cross-sectional diabetes survey was conducted in 2006 and 2009 in Qingdao, separately. 4400 participants (1 793 men and 2607 women) were include in current analysis. IFG/IGT was defined according to fasting plasma glucose (FPG) and/or 2 h post-load plasma glucose (2 h PG). Logistic regression models and areas under receiver operating characteristic curves (AUROC) were performed to estimate the associations between TG, TC levels and IFG/IGT. Results: Spearman analysis showed that serum TG and TC was independently and positively associated with FPG and 2 h PG. As compared with normoglycaemia, the odds ratio[(95% confidence intervals), OR(95% CI)] for IFG/IGT corresponding to hypertriglyceridemia (HTG) were 1.61 (1.17, 2.22) in men and 1.57(1.15, 2.14) in women for TG and accompany with Hypercholesterolemia (HTC) 1.56 (1.15, 2.13) and 1.20 (0.93, 1.54) for TC, when adjusting for confounding factor. The AUROCs of TG, TC for IFG/IGT were relatively smaller (0.50 <AUROC <0.7) in both gender. The optimal cut-offs for TG and TC was 1.61, 4.91 in men and 1.24, 5.32 in women, respectively. Conclusions: Evaluated TG in both gender and TC in men were independently associated with the present of the IFG/IGT, yet, could not be an authentic predictors of IFG/IGT in both men and women in current Chinese population.Peer reviewe

Structural transition, electric transport, and electronic structures in the compressed trilayer nickelate La4Ni3O10

Atomic structure and electronic band structure are fundamental properties for understanding the mechanism of superconductivity. Motivated by the discovery of pressure-induced high-temperature superconductivity at 80 K in the bilayer Ruddlesden-Popper nickelate La3Ni2O7, the atomic structure and electronic band structure of the trilayer nickelate La4Ni3O10 under pressure up to 44.3 GPa are investigated. A structural transition from the monoclinic P21/a space group to the tetragonal I4/mmm around 12.6-13.4 GPa is identified, accompanying with a drop of resistance below 7 K. Density functional theory calculations suggest that the bonding state of Ni 3dz2 orbital rises and crosses the Fermi level at high pressures, which may give rise to possible superconductivity observed in resistance under pressure in La4Ni3O10. The trilayer nickelate La4Ni3O10 shows some similarities with the bilayer La3Ni2O7 and has unique properties, providing a new platform to investigate the underlying mechanism of superconductivity in nickelates.Comment: 19 pages, 4 figure

Orbital-Dependent Electron Correlation in Double-Layer Nickelate La3Ni2O7

The latest discovery of high temperature superconductivity near 80K in La3Ni2O7 under high pressure has attracted much attention. Many proposals are put forth to understand the origin of superconductivity. The determination of electronic structures is a prerequisite to establish theories to understand superconductivity in nickelates but is still lacking. Here we report our direct measurement of the electronic structures of La3Ni2O7 by high-resolution angle-resolved photoemmission spectroscopy. The Fermi surface and band structures of La3Ni2O7 are observed and compared with the band structure calculations. A flat band is formed from the Ni-3dz2 orbitals around the zone corner which is 50meV below the Fermi level. Strong electron correlations are revealed which are orbital- and momentum-dependent. Our observations will provide key information to understand the origin of high temperature superconductivity in La3Ni2O7.Comment: 18 pages, 4 figure

18F-FDG PET/CT findings in fatal Balamuthia Mandrillaris encephalitis in brain stem: A case report

We presented a case of a 66-year-old female whose initial symptom was headache without obvious inducement. The patient's condition progressed rapidly to a semi-coma state after symptomatic treatment. The 18F-FDG PET/CT scan revealed circular FDG hypermetabolism and central metabolic defect of the pons and left frontal lobe lesions. The combination of clinical findings, MRI, and Metagenomic next-generation sequencing (NGS) of cerebrospinal fluid led to the diagnosis of Balamuthia mandrillaris encephalitis. The patient died 5 days after discharge

Risk mapping of scrub typhus infections in Qingdao city, China

BACKGROUND: The emergence and re-emergence of scrub typhus has been reported in the past decade in many global regions. In this study, we aim to identify potential scrub typhus infection risk zones with high spatial resolution in Qingdao city, in which scrub typhus is endemic, to guide local prevention and control strategies.METHODOLOGY/PRINCIPAL FINDINGS: Scrub typhus cases in Qingdao city during 2006-2018 were retrieved from the Chinese National Infectious Diseases Reporting System. We divided Qingdao city into 1,101 gridded squares and classified them into two categories: areas with and without recorded scrub typhus cases. A boosted regression tree model was used to explore environmental and socioeconomic covariates associated with scrub typhus occurrence and predict the risk of scrub typhus infection across the whole area of Qingdao city. A total of 989 scrub typhus cases were reported in Qingdao from 2006-2018, with most cases located in rural and suburban areas. The predicted risk map generated by the boosted regression tree models indicated that the highest infection risk areas were mainly concentrated in the mid-east and northeast regions of Qingdao, with gross domestic product (20.9%±1.8% standard error) and annual cumulative precipitation (20.3%±1.1%) contributing the most to the variation in the models. By using a threshold environmental suitability value of 0.26, we identified 757 squares (68.7% of the total) with a favourable environment for scrub typhus infection; 66.2% (501/757) of the squares had not yet recorded cases. It is estimated that 6.32 million people (72.5% of the total population) reside in areas with a high risk of scrub typhus infection.CONCLUSIONS/SIGNIFICANCE: Many locations in Qingdao city with no recorded scrub typhus cases were identified as being at risk for scrub typhus occurrence. In these at-risk areas, awareness and capacity for case diagnosis and treatment should be enhanced in the local medical service institutes.</p