Targeting mPGES-2 to protect against acute kidney injury via inhibition of ferroptosis dependent on p53

Abstract Acute kidney injury (AKI) is a clinical syndrome with high morbidity and mortality but no specific therapy. Microsomal prostaglandin E synthase-2 (mPGES-2) is a PGE2 synthase but can metabolize PGH2 to malondialdehyde by forming a complex with heme. However, the role and mechanism of action of mPGES-2 in AKI remain unclear. To examine the role of mPGES-2, both global and tubule-specific mPGES-2-deficient mice were treated with cisplatin to induce AKI. mPGES-2 knockdown or overexpressing HK-2 cells were exposed to cisplatin to cause acute renal tubular cell injury. The mPGES-2 inhibitor SZ0232 was used to test the translational potential of targeting mPGES-2 in treating AKI. Additionally, mice were subjected to unilateral renal ischemia/reperfusion to further validate the effect of mPGES-2 on AKI. Interestingly, both genetic and pharmacological blockage of mPGES-2 led to decreased renal dysfunction and morphological damage induced by cisplatin and unilateral renal ischemia/reperfusion. Mechanistic exploration indicated that mPGES-2 deficiency inhibited ferroptosis via the heme-dependent regulation of the p53/SLC7A11/GPX4 axis. The present study indicates that mPGES-2 blockage may be a promising therapeutic strategy for AKI

Look into the HIV Epidemic of Gay Community with a Socio-Cultural Perspective: A Qualitative Study in China, 2015-2016.

Current Chinese studies continue to view male homosexuality through a disease focused lens which pays limited attention to socio-cultural aspects of sexual behavior and HIV transmission. This qualitative study aimed to investigate how socio-cultural factors influence gay men's sexual beliefs and behaviors in contemporary China, and their implications for HIV epidemic.Qualitative methodology was used in this study. During 2015-2016, in-depth interviews were conducted with 61 self identified gay men in Jiangxi, Henan, Heilongjiang, Guangdong, Jiangsu provinces and Chongqing municipality of China. Our study revealed that: 1) influenced by Chinese traditional culture, gay men have conflicts on self-identity, which led to low self-acceptance and negative attitude on sex, and huge socio-psychological stress; 2) a generational differences within gay community was observed, reflected in varied sexual attitudes and practices as well as way for approaching new friends, both of which have implications and challenges on HIV control and prevention; 3) socio-cultural barriers, including open minds towards casual sex and nonmonogamous relationship, and low priority of health demands were widely observed and led to negative coping with AIDS among gay community.It is essential to take a holistic view into gay men's HIV epidemic in China. Socio-cultural barriers for HIV control and prevention found in this study call for serious and imperative consideration on integrated measures, including targeted efforts towards effective sex education and further inclusion of socio-cultural perspectives in HIV/AIDS interventions for gay men

Solution-Processable Organic Molecule Photovoltaic Materials with Bithienyl-benzodithiophene Central Unit and Indenedione End Groups

Two solution-processable acceptor–donor–acceptor (A-D-A) structured organic molecules with bithienyl-substituted benzodithiophene (BDTT) as central and donor unit, indenedione (ID) as acceptor unit and end groups, and thiophene (T) or bithiophene (bT) as π-bridges, D1 and D2, are designed and synthesized for the application as donor materials in organic solar cells (OSCs). Two corresponding molecules with alkoxy side chains on BDT, DO1, and DO2 are also synthesized for comparison. The four compounds possess broad absorption covering the wavelength range 450–740 nm and relatively lower HOMO energy levels from −5.16 to about −5.19 eV. D2 and DO2 with bithiophene π-bridges demonstrate stronger absorbance and higher hole mobilities than the compounds with thiophene π-bridges. The power conversion efficiency (PCE) values of the OSCs based on the organic compounds/PC₇₀BM (1.5:1, w/w) are 6.75% for D2, 5.67% for D1, 5.11% for DO2, and 4.15% for DO1. The results indicate that the molecules with thienyl conjugated side chains and bithiophene π-bridges show better photovoltaic performance. The PCE of the D2-based OSC are among the highest values in the OSCs based on the solution-processed organic small molecules

Informants’ Characteristics.

<p>Informants’ Characteristics.</p