Shandong University

About: Shandong University is a education organization based out in Jinan, Shandong, China. It is known for research contribution in the topics: Laser & Cancer. The organization has 99070 authors who have published 99160 publications receiving 1625094 citations. The organization is also known as: Shāndōng Dàxué.

RND-type drug efflux pumps from Gram-negative bacteria: molecular mechanism and inhibition.

Abstract: Drug efflux protein complexes confer multidrug resistance on bacteria by transporting a wide spectrum of structurally diverse antibiotics. Moreover, organisms can only acquire resistance in the presence of an active efflux pump. The substrate range of drug efflux pumps is not limited to antibiotics, but it also includes toxins, dyes, detergents, lipids and molecules involved in quorum sensing; hence efflux pumps are also associated with virulence and biofilm formation. Inhibitors of efflux pumps are therefore attractive compounds to reverse multidrug resistance and to prevent the development of resistance in clinically relevant bacterial pathogens. Recent successes on the structure determination and functional analysis of the AcrB and MexB components of the AcrAB-TolC and MexAB-OprM drug efflux systems as well as the structure of the fully assembled, functional triparted AcrAB-TolC complex significantly contributed to our understanding of the mechanism of substrate transport and the options for inhibition of efflux. These data, combined with the well-developed methodologies for measuring efflux pump inhibition, could allow the rational design and subsequent experimental verification of potential efflux pump inhibitors. In this review we will explore how the available biochemical and structural information can be translated into the discovery and development of new compounds that could reverse drug resistance in Gram-negative pathogens. The current literature on efflux pump inhibitors will also be analysed and the reasons why no compounds have yet progressed into clinical use will be explored.

[Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia].

Abstract: The novel coronavirus 2019 (COVID-19) infected patients by binding human ACE2, leading to severe pneumonia and highly mortality rate in patients. At present, there is no definite and effective treatment for COVID-19. ACE2 plays an important role in the RAS, and the imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7)/Mas receptor pathway in the RAS system will lead to multi-system inflammation. Increased ACE and Ang II are poor prognostic factors for severe pneumonia. Animal studies have shown that RAS inhibitors could effectively relieve symptoms of acute severe pneumonia and respiratory failure. The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited. The balance of the RAS system was broken, and this would lead to the exacerbation of acute severe pneumonia. Therefore, we speculate that ACEI and AT1R inhibitors could be used in patients with COVID-19 pneumonia under the condition of controlling blood pressure, and might reduce the pulmonary inflammatory response and mortality.

Measurement of the Reactor Antineutrino Flux and Spectrum at Daya Bay

Abstract: This Letter reports a measurement of the flux and energy spectrum of electron antineutrinos from six 2.9 GWth nuclear reactors with six detectors deployed in two near (effective baselines 512 and 561 m) and one far (1579 m) underground experimental halls in the Daya Bay experiment. Using 217 days of data, 296 721 and 41 589 inverse β decay (IBD) candidates were detected in the near and far halls, respectively. The measured IBD yield is (1.55±0.04) ×10(-18) cm(2) GW(-1) day(-1) or (5.92±0.14) ×10(-43) cm(2) fission(-1). This flux measurement is consistent with previous short-baseline reactor antineutrino experiments and is 0.946±0.022 (0.991±0.023) relative to the flux predicted with the Huber-Mueller (ILL-Vogel) fissile antineutrino model. The measured IBD positron energy spectrum deviates from both spectral predictions by more than 2σ over the full energy range with a local significance of up to ∼4σ between 4-6 MeV. A reactor antineutrino spectrum of IBD reactions is extracted from the measured positron energy spectrum for model-independent predictions.