We report a new search for weakly interacting massive particles (WIMPs) using the combined low background data sets acquired in 2016 and 2017 from the PandaX-II experiment in China. The latest data set contains a new exposure of 77.1 live days, with the background reduced to a level of 0.8×10^{-3}  evt/kg/day, improved by a factor of 2.5 in comparison to the previous run in 2016. No excess events are found above the expected background. With a total exposure of 5.4×10^{4}  kg day, the most stringent upper limit on the spin-independent WIMP-nucleon cross section is set for a WIMP with mass larger than 100  GeV/c^{2}, with the lowest 90% C.L. exclusion at 8.6×10^{-47}  cm^{2} at 40  GeV/c^{2}.

In vitro and some animal models have shown that quercetin, a polyphenol derived from plants, has a wide range of biological actions including anti-carcinogenic, anti-inflammatory and antiviral activities; as well as attenuating lipid peroxidation, platelet aggregation and capillary permeability. This review focuses on the physicochemical properties, dietary sources, absorption, bioavailability and metabolism of quercetin, especially main effects of quercetin on inflammation and immune function. According to the results obtained both in vitro and in vivo, good perspectives have been opened for quercetin. Nevertheless, further studies are needed to better characterize the mechanisms of action underlying the beneficial effects of quercetin on inflammation and immunity.

Since the first successful synthesis of graphene just over a decade ago, a variety of twodimensional (2D) materials (e.g., transition metal-dichalcogenides, hexagonal boron-nitride, etc.) have been discovered. Among the many unique and attractive properties of 2D materials, mechanical properties play important roles in manufacturing, integration and performance for their potential applications. Mechanics is indispensable in the study of mechanical properties, both experimentally and theoretically. The coupling between the mechanical and other physical properties (thermal, electronic, optical) is also of great interest in exploring novel applications, where mechanics has to be combined with condensed matter physics to establish a scalable theoretical framework. Moreover, mechanical interactions between 2D materials and various substrate materials are essential for integrated device applications of 2D materials, for which the mechanics of interfaces (adhesion and friction) has to be developed for the 2D materials. Here we review recent theoretical and experimental works related to mechanics and mechanical properties of 2D materials. While graphene is the most studied 2D material to date, we expect continual growth of interest in the mechanics of other 2D materials beyond graphene.

Background Mucus stasis in chronic obstructive pulmonary disease (COPD) is a significant contributor to morbidity and mortality. Potentiators of cystic fibrosis transmembrane conductance regulator (CFTR) activity pharmacologically enhance CFTR function; ivacaftor is one such agent approved to treat CF patients with the G551D-CFTR gating mutation. CFTR potentiators may also be useful for other diseases of mucus stasis, including COPD. Methods and Findings In primary human bronchial epithelial cells, exposure to cigarette smoke extract diminished CFTR-mediated anion transport (65.8±0.2% of control, P<0.005) and mucociliary transport (0.17±0.05 µm/sec vs. 2.4±0.47 µm/sec control, P<0.05) by reducing airway surface liquid depth (7.3±0.6 µm vs. 13.0±0.6 µm control, P<0.005) and augmenting mucus expression (by 64%, P<0.05) without altering transepithelial resistance. Smokers with or without COPD had reduced CFTR activity measured by nasal potential difference compared to age-matched non-smokers (−6.3±1.4 and −8.0±2.0 mV, respectively vs. −15.2±2.7 mV control, each P<0.005, n = 12–14/group); this CFTR decrement was associated with symptoms of chronic bronchitis as measured by the Breathlessness Cough and Sputum Score (r = 0.30, P<0.05) despite controlling for smoking (r = 0.31, P<0.05). Ivacaftor activated CFTR-dependent chloride transport in non-CF epithelia and ameliorated the functional CFTR defect induced by smoke to 185±36% of non-CF control (P<0.05), thereby increasing airway surface liquid (from 7.3±0.6 µm to 10.1±0.4 µm, P<0.005) and mucociliary transport (from 0.27±0.11 µm/s to 2.7±0.28 µm/s, P<0.005). Conclusions Cigarette smoking reduces CFTR activity and is causally related to reduced mucus transport in smokers due to inhibition of CFTR dependent fluid transport. These effects are reversible by the CFTR potentiator ivacaftor, representing a potential therapeutic strategy to augment mucociliary clearance in patients with smoking related lung disease.

Bromodomain and extraterminal domain (BET) protein inhibitors are emerging as promising anti-cancer therapies. The gene encoding the E3 ubiquitin ligase substrate-binding adaptor speckle-type POZ protein (SPOP) is most frequently mutated in prostate cancer. Here we demonstrate that wild-type SPOP binds to and induces ubiquitination and proteasomal degradation of BET proteins (BRD2, BRD3 and BRD4) by recognizing a common degron motif. In contrast, prostate cancer-associated SPOP mutants impair binding and proteasomal degradation of BET proteins, thus inducing their accumulation in prostate cancer cells and patient specimens. Transcriptome and BRD4 cistrome analyses reveal that SPOP mutation enhances BRD4-dependent expression of GTPase RAC1 and cholesterol biosynthesis genes and AKT-mTORC1 activation. SPOP mutant expression confers BET inhibitor resistance and this effect can be overcome by AKT inhibitors. Thus, SPOP mutations promote AKT-mTORC1 activation and intrinsic BET inhibitor resistance by stabilizing BET proteins, suggesting that SPOP mutation can be an effective biomarker to guide BET inhibitor-oriented therapy of prostate cancer.

Graphene has emerged as a promising material for photonic applications fuelled by its superior electronic and optical properties. However, the photoresponsivity is limited by the low absorption cross-section and ultrafast recombination rates of photoexcited carriers. Here we demonstrate a photoconductive gain of ∼105 electrons per photon in a carbon nanotube–graphene hybrid due to efficient photocarriers generation and transport within the nanostructure. A broadband photodetector (covering 400–1,550 nm) based on such hybrid films is fabricated with a high photoresponsivity of >100 A W−1 and a fast response time of ∼100 μs. The combination of ultra-broad bandwidth, high responsivities and fast operating speeds affords new opportunities for facile and scalable fabrication of all-carbon optoelectronic devices.

We demonstrate the use of a high resolution form of optical coherence tomography, termed micro-OCT (μOCT), for investigating the functional microanatomy of airway epithelia. μOCT captures several key parameters governing the function of the airway surface (airway surface liquid depth, periciliary liquid depth, ciliary function including beat frequency, and mucociliary transport rate) from the same series of images and without exogenous particles or labels, enabling non-invasive study of dynamic phenomena. Additionally, the high resolution of μOCT reveals distinguishable phases of the ciliary stroke pattern and glandular extrusion. Images and functional measurements from primary human bronchial epithelial cell cultures and excised tissue are presented and compared with measurements using existing gold standard methods. Active secretion from mucus glands in tissue, a key parameter of epithelial function, was also observed and quantified.

Hypoxia-ischemia (H-I) is frequently observed in perinatal asphyxia and other diseases. It can lead to serious cardiac injury, cerebral damage, neurological disability and mortality. Previous studies have demonstrated that the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) signaling pathway, which regulates a wide range of cellular functions, is involved in the resistance response to H-I through the activation of proteins associated with survival and inactivation of apoptosis-associated proteins. It can also regulate the expression of hypoxia-induced factor-1α (HIF-1α). HIF-1α can further regulate the expression of downstream proteins involved in glucose metabolism and angiogenesis, such as vascular endothelial growth factor and erythropoietin, to facilitate ischemic adaptation. Notably, HIF-1α may also induce detrimental effects. The effects of HIF-1 on ischemic outcomes may be dependent on the H-I duration, animal age and species. Thus, further investigation of the PI3K/Akt signaling pathway may provide further insights of the potential targets for treating diseases accompanied by H-I.