Simultaneously expressed miR-424 and miR-381 synergistically suppress the proliferation and survival of renal cancer cells---Cdc2 activity is up-regulated by targeting WEE1

OBJECTIVES: MiRNAs are intrinsic RNAs that interfere with protein translation. Few studies on the synergistic effects of miRNAs have been reported. Both miR-424 and miR-381 have been individually reported to be involved in carcinogenesis. They share a common putative target, WEE1, which is described as an inhibitor of G2/M progression. Here, we studied the synergistic effects of miR-424 and miR-381 on renal cancer cells. METHODS: The viability of 786-O cells was analyzed after transfection with either a combination of miR-424 and miR-381 or each miRNA alone. We investigated cell cycle progression and apoptosis with flow cytometry. To confirm apoptosis and the abrogation of G2/M arrest, we determined the level of pHH3, which is an indicator of mitosis, and caspase-3/7 activity. The expression levels of WEE1, Cdc25, γH2AX, and Cdc2 were manipulated to investigate the roles of these proteins in the miRNA-induced anti-tumor effects. To verify that WEE1 was a direct target of both miR-424 and miR-381, we performed a dual luciferase reporter assay. RESULTS: We showed that the combination of these miRNAs synergistically inhibited proliferation, abrogated G2/M arrest, and induced apoptosis. This combination led to Cdc2 activation through WEE1 inhibition. This regulation was more effective when cells were treated with both miRNAs than with either miRNA alone, indicating synergy between these miRNAs. WEE1 was verified to be a direct target of each miRNA according to the luciferase reporter assay. CONCLUSIONS: These data clearly demonstrate that these two miRNAs might synergistically act as novel modulators of tumorigenesis by down-regulating WEE1 expression in renal cell cancer cells

Mental health stigma and mental health knowledge in Chinese population:a cross-sectional study

BACKGROUND: Little is known about the public stigma on mental illness and mental health knowledge (MHK) in China, public stigma and low MHK can negatively affect patients' health and increase the burden of mental disorders on society. This study aimed at investigating the rates of stigma and MHK, the correlates of stigma and MHK, and the association between MHK and stigma among a Chinese population. METHODS: The data is from the Tianjin Mental Health Survey (TJMHS), which involved a large and a representative sample of adult community residents in the Chinese municipality of Tianjin (n = 11,748). In a 12% random subsample (n = 1775) the Perceived Discrimination and Devaluation scale (PDD) and a Mental Health Knowledge Questionnaire (MHKQ) were administered. First, percentages of the responses to the individual items of the PDD and MHKQ were investigated. Second, sociodemographic correlates of PDD and MHK, and the association between stigma and MHK were investigated. RESULTS: We found that a sizable proportion of participants responded that others would hold a negative attitude towards (former) mental patients, especially with regard to engaging in closer personal relationships. Most people were not familiar about the causes, treatments and prevention of mental illness. Resident area, age, education level, Per capita family income and employment status were related to devaluation score and MHKQ score. MHK was negatively associated with public stigma. CONCLUSIONS: There is room for improvement with regard to levels of public stigma and MHK in China. Providing psychoeducation to improve public MHK could also contribute to reduction of public stigma

(−)-Dimethyl 3,3′-diphenyl-2,2′-[pyridine-2,6-diylbis(carbonyl­imino)]dipropanoate

The title compound, C27H27N3O6, a bis-amide derivative, is also a chiral amino acid ester with l-phenyl­alanine methyl ester groups as amine substituents. The pyridine ring is oriented at dihedral angles of 89.69 (3) and 62.95 (3)° with respect to the phenyl rings, while the dihedral angle between the phenyl rings is 60.76 (3)°. In the crystal structure, inter­molecular N—H⋯O hydrogen bonds link the mol­ecules into chains. One of the carbonyl O atoms and one of the meth­oxy CH3 groups are disordered over two positions. The O atom was refined with occupancies of 0.69 (13) and 0.31 (13), while C and H atoms were refined with occupancies of 0.69 (8) and 0.31 (8)

Continued spread of HIV among injecting drug users in southern Sichuan Province, China

OBJECTIVE: To estimate HIV prevalence among injecting drug users (IDUs) in a drug trafficking city in southwest Sichuan Province, China. METHODS: A total of 314 IDUs was invited to participate in the cross-sectional survey in 2004 through community outreach recruitment and peer referrals. Blood sample was taken for HIV antibody testing and a structured questionnaire was administered to collect information on socio-demographics, drug using and sexual behaviors. RESULTS: HIV prevalence among IDUs was 17.8% (56/314), about one half higher than that in previous survey in 2002 (11.3%, 43/379). Yi and other minority ethnicity (Odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7–5.8; P < 0.001), and total times of sharing injecting equipments 1–9 times versus none, OR, 2.7; 95% CI 1.2–6.2; P = 0.02; and ≥10 times versus none, OR, 7.5; 95% CI, 3.2–17.7; P < 0.001) were independent risk factors for HIV infection. CONCLUSION: IDUs with high prevalence rates of HIV and equipment sharing behavior in the drug trafficking city may serve a source for further spread of HIV to other areas in China. The increasing trend of HIV epidemic among IDUs underscores the urgency of scaling up interventions

Effects of sewer conditions on the degradation of selected illicit drug residues in wastewater

The stability of five illicit drug markers in wastewater was tested under different sewer conditions using laboratory-scale sewer reactors. Wastewater was spiked with deuterium labelled isotopes of cocaine, benzoyl ecgonine, methamphetamine, MDMA and 6-acetyl morphine to avoid interference from the native isotopes already present in the wastewater matrix. The sewer reactors were operated at 20°C and pH 7.5, and wastewater was sampled at 0, 0.25, 0.5, 1, 2, 3, 6, 9 and 12h to measure the transformation/degradation of these marker compounds. The results showed that while methamphetamine, MDMA and benzoyl ecgonine were stable in the sewer reactors, cocaine and 6-acetyl morphine degraded quickly. Their degradation rates are significantly higher than the values reportedly measured in wastewater alone (without biofilms). All the degradation processes followed first order kinetics. Benzoyl ecgonine and morphine were also formed from the degradation of cocaine and 6-acetyl morphine, respectively, with stable formation rates throughout the test. These findings suggest that, in sewage epidemiology, it is essential to have relevant information of the sewer system (i.e. type of sewer, hydraulic retention time) in order to accurately back-estimate the consumption of illicit drugs. More research is required to look into detailed sewer conditions (e.g. temperature, pH and ratio of biofilm area to wastewater volume among others) to identify their effects on the fate of illicit drug markers in sewer systems

Chinese version of Dominic Interactive – A self-report video game for assessing mental health in young children

ObjectivesAssess the validity of the Chinese version of the Dominic Interactive (DI), a 91-item, video-based diagnostic screening instrument for children that assesses four internalized disorders (phobias, separation anxiety disorder, generalized anxiety disorder, and major depressive disorder) and three externalized disorders (attention-deficit/hyperactivity disorder, conduct disorder, oppositional defiant disorder).Methods(1) Compare DI-generated “probable” or “possible” diagnoses to diagnoses based on the Development and Well-Being Assessment (DAWBA) instrument in 113 psychiatric outpatients and 20 community controls. (2) Administer DI to 1,479 children from elementary schools in Tianjin.ResultsIn the validation sample, DI with DAWBA concordance was much greater for internalized disorders (mean Kappa = 0.56) than for externalized disorders (mean kappa = 0.11). The positive predictive value of DI diagnoses ranged from 0.96 (generalized anxiety disorder) to 25% (oppositional defiant disorder) and negative from 0.81 to 0.96. Using “probable” cuts provides better results. In the survey, prevalence of probable DI disorders ranged from 1.0% (conduct disorder) to 13.1% (phobias). Internal consistency of all DI items was excellent (Cronbach alpha = 0.93) and that of the seven subscales ranged from 0.64 (phobias) to 0.87 (major depressive disorder). In multilevel SEM analyses, SRMR (Standardized root mean square residual) or each of the seven diagnoses was below 0.08 and each coefficient of determination was below 0.60.ConclusionThe Chinese DI is a convenient method of screening common mental disorders in Chinese children mainly for internalized disorders, which are the most prevalent diagnoses in that population. However its high negative predictive values for externalized could be used for screening

Fermion-boson many-body interplay in a frustrated kagome paramagnet

Kagome-net, appearing in areas of fundamental physics, materials, photonic and cold-atom systems, hosts frustrated fermionic and bosonic excitations. However, it is extremely rare to find a system to study both fermionic and bosonic modes to gain insights into their many-body interplay. Here we use state-of-the-art scanning tunneling microscopy and spectroscopy to discover unusual electronic coupling to flat-band phonons in a layered kagome paramagnet. Our results reveal the kagome structure with unprecedented atomic resolution and observe the striking bosonic mode interacting with dispersive kagome electrons near the Fermi surface. At this mode energy, the fermionic quasi-particle dispersion exhibits a pronounced renormalization, signaling a giant coupling to bosons. Through a combination of self-energy analysis, first-principles calculation, and a lattice vibration model, we present evidence that this mode arises from the geometrically frustrated phonon flat-band, which is the lattice analog of kagome electron flat-band. Our findings provide the first example of kagome bosonic mode (flat-band phonon) in electronic excitations and its strong interaction with fermionic degrees of freedom in kagome-net materials.Comment: To appear in Nature Communications (2020

Challenges in QCD matter physics - The Compressed Baryonic Matter experiment at FAIR

Substantial experimental and theoretical efforts worldwide are devoted to explore the phase diagram of strongly interacting matter. At LHC and top RHIC energies, QCD matter is studied at very high temperatures and nearly vanishing net-baryon densities. There is evidence that a Quark-Gluon-Plasma (QGP) was created at experiments at RHIC and LHC. The transition from the QGP back to the hadron gas is found to be a smooth cross over. For larger net-baryon densities and lower temperatures, it is expected that the QCD phase diagram exhibits a rich structure, such as a first-order phase transition between hadronic and partonic matter which terminates in a critical point, or exotic phases like quarkyonic matter. The discovery of these landmarks would be a breakthrough in our understanding of the strong interaction and is therefore in the focus of various high-energy heavy-ion research programs. The Compressed Baryonic Matter (CBM) experiment at FAIR will play a unique role in the exploration of the QCD phase diagram in the region of high net-baryon densities, because it is designed to run at unprecedented interaction rates. High-rate operation is the key prerequisite for high-precision measurements of multi-differential observables and of rare diagnostic probes which are sensitive to the dense phase of the nuclear fireball. The goal of the CBM experiment at SIS100 (sqrt(s_NN) = 2.7 - 4.9 GeV) is to discover fundamental properties of QCD matter: the phase structure at large baryon-chemical potentials (mu_B > 500 MeV), effects of chiral symmetry, and the equation-of-state at high density as it is expected to occur in the core of neutron stars. In this article, we review the motivation for and the physics programme of CBM, including activities before the start of data taking in 2022, in the context of the worldwide efforts to explore high-density QCD matter.Comment: 15 pages, 11 figures. Published in European Physical Journal