Backscattering suppression in silicon-on-insulator (SOI) is one of the central issues to reduce energy loss and signal distortion, enabling for capability improvement of modern information processing ...systems. Valley physics provides an intriguing way for robust information transfer and unidirectional coupling in topological nanophotonics. Here we realize topological transport in a SOI valley photonic crystal slab. Localized Berry curvature near zone corners guarantees the existence of valley-dependent edge states below light cone, maintaining in-plane robustness and light confinement simultaneously. Topologically robust transport at telecommunication is observed along two sharp-bend interfaces in subwavelength scale, showing flat-top high transmission of ~10% bandwidth. Topological photonic routing is achieved in a bearded-stack interface, due to unidirectional excitation of valley-chirality-locked edge state from the phase vortex of a nanoscale microdisk. These findings show the prototype of robustly integrated devices, and open a new door towards the observation of non-trivial states even in non-Hermitian systems.
Statins: a repurposed drug to fight cancer Jiang, Wen; Hu, Jin-Wei; He, Xu-Ran ...
Journal of experimental & clinical cancer research,
07/2021, Volume:
40, Issue:
1
Journal Article
Peer reviewed
Open access
As competitive HMG-CoA reductase (HMGCR) inhibitors, statins not only reduce cholesterol and improve cardiovascular risk, but also exhibit pleiotropic effects that are independent of their ...lipid-lowering effects. Among them, the anti-cancer properties of statins have attracted much attention and indicated the potential of statins as repurposed drugs for the treatment of cancer. A large number of clinical and epidemiological studies have described the anticancer properties of statins, but the evidence for anticancer effectiveness of statins is inconsistent. It may be that certain molecular subtypes of cancer are more vulnerable to statin therapy than others. Whether statins have clinical anticancer effects is still an active area of research. Statins appear to enhance the efficacy and address the shortcomings associated with conventional cancer treatments, suggesting that statins should be considered in the context of combined therapies for cancer. Here, we present a comprehensive review of the potential of statins in anti-cancer treatments. We discuss the current understanding of the mechanisms underlying the anti-cancer properties of statins and their effects on different malignancies. We also provide recommendations for the design of future well-designed clinical trials of the anti-cancer efficacy of statins.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Microglial activation and neuroinflammation induced by amyloid β (Aβ) play pivotal roles in Alzheimer’s disease (AD) pathogenesis. Astragaloside IV (AS-IV) is one of the major active compounds of the ...traditional Chinese medicine Astmgali Radix. It has been reported that AS-IV could protect against Aβ-induced neuroinflammation and cognitive impairment, but the underlying mechanisms need to be further clarified. In this study, the therapeutic effects of AS-IV were investigated in an oligomeric Aβ (oAβ) induced AD mice model. The effects of AS-IV on microglial activation, neuronal damage and reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression were further studied. Different doses of AS-IV were administered intragastrically once a day after intracerebroventricularly oAβ injection. Results of behavioral experiments including novel object recognition (NOR) test and Morris water maze (MWM) test revealed that AS-IV administration could significantly ameliorate oAβ-induced cognitive impairment in a dose dependent manner. Enzyme linked immunosorbent assay (ELISA) results showed that increased levels of reactive oxygen species (ROS), tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and IL-6 in hippocampal tissues induced by oAβ injection were remarkably inhibited after AS-IV treatment. OAβ induced microglial activation and neuronal damage was significantly suppressed in AS-IV-treated mice brain, observed in immunohistochemistry results. Furthermore, oAβ upregulated protein expression of NADPH oxidase subunits gp91phox, p47phox, p22phox and p67phox were remarkably reduced by AS-IV in Western blotting assay. These results revealed that AS-IV could ameliorate oAβ-induced cognitive impairment, neuroinflammation and neuronal damage, which were possibly mediated by inhibition of microglial activation and down-regulation of NADPH oxidase protein expression. Our findings provide new insights of AS-IV for the treatment of neuroinflammation related diseases such as AD.
Profiting from the sustained clinical improvement and prolonged patient survival, immune checkpoint blockade of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) axis has ...emerged as a revolutionary cancer therapy approach. However, the anti-PD-1/PD-L1 antibodies only achieve a clinical response rate of approximately 20%. Herein, we identified a novel combination strategy that Chinese medicine ginseng-derived ginsenoside Rh2 (Rh2) markedly improved the anti-cancer efficacy of anti-PD-L1 antibody in mice bearing MC38 tumor. Rh2 combined with anti-PD-L1 antibody (combo treatment) further triggered the infiltration, proliferation and activation of CD8+ T cells in the tumor microenvironment (TME). Depletion of CD8+ T cells by mouse CD8 blocking antibody abolished the anti-cancer effect of combo treatment totally. Mechanistically, combo treatment further increased the expression of CXCL10 through activating TBK1-IRF3 signaling pathway, explaining the increased infiltration of T cells. Employing anti- CXC chemokine receptor 3 (CXCR3) blocking antibody prevented the T cells infiltration and abolished the anti-cancer effect of combo treatment. Meanwhile, combo treatment increased the percentage of M1-like macrophages and raised the ratio of M1/M2 macrophages in TME. By comparing the anti-cancer effect of combo treatment among MC38, CT26 and 4T1 tumors, resident T cells were considered as a prerequisite for the effectiveness of combo treatment. These findings demonstrated that Rh2 potentiated the anti-cancer effect of PD-L1 blockade via promoting the T cells infiltration and activation, which shed a new light on the combination strategy to enhance anti-PD-L1 immunotherapy by using natural product Rh2.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA ...sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation.
Abstract
Vasoactive intestinal polypeptide receptor (VIP1R) is a widely expressed class B G protein-coupled receptor and a drug target for the treatment of neuronal, metabolic, and inflammatory ...diseases. However, our understanding of its mechanism of action and the potential of drug discovery targeting this receptor is limited by the lack of structural information of VIP1R. Here we report a cryo-electron microscopy structure of human VIP1R bound to PACAP27 and Gs heterotrimer, whose complex assembly is stabilized by a NanoBiT tethering strategy. Comparison with other class B GPCR structures reveals that PACAP27 engages VIP1R with its N-terminus inserting into the ligand binding pocket at the transmembrane bundle of the receptor, which subsequently couples to the G protein in a receptor-specific manner. This structure has provided insights into the molecular basis of PACAP27 binding and VIP receptor activation. The methodology of the NanoBiT tethering may help to provide structural information of unstable complexes.
The mixed halide perovskites have emerged as outstanding light absorbers for efficient solar cells. Unfortunately, it reveals inhomogeneity in these polycrystalline films due to composition ...separation, which leads to local lattice mismatches and emergent residual strains consequently. Thus far, the understanding of these residual strains and their effects on photovoltaic device performance is absent. Herein we study the evolution of residual strain over the films by depth-dependent grazing incident X-ray diffraction measurements. We identify the gradient distribution of in-plane strain component perpendicular to the substrate. Moreover, we reveal its impacts on the carrier dynamics over corresponding solar cells, which is stemmed from the strain induced energy bands bending of the perovskite absorber as indicated by first-principles calculations. Eventually, we modulate the status of residual strains in a controllable manner, which leads to enhanced PCEs up to 20.7% (certified) in devices via rational strain engineering.
Tin‐based perovskites with narrow bandgaps and high charge‐carrier mobilities are promising candidates for the preparation of efficient lead‐free perovskite solar cells (PSCs). However, the ...crystalline rate of tin‐based perovskites is much faster, leading to abundant trap states and much lower open‐circuit voltage (Voc). Here, hydrogen bonding is introduced to retard the crystalline rate of the FASnI3 perovskite. By adding poly(vinyl alcohol) (PVA), the OH…I− hydrogen bonding interactions between PVA and FASnI3 have the effects of introducing nucleation sites, slowing down the crystal growth, directing the crystal orientation, reducing the trap states, and suppressing the migration of the iodide ions. In the presence of the PVA additive, the FASnI3–PVA PSCs attain higher power conversion efficiency of 8.9% under a reverse scan with significantly improved Voc from 0.55 to 0.63 V, which is one of the highest Voc values for FASnI3‐based PSCs. More importantly, the FASnI3–PVA PSCs exhibit striking long‐term stability, with no decay in efficiency after 400 h of operation at the maximum power point. This approach, which makes use of the OH…I− hydrogen bonding interactions between PVA and FASnI3, is generally applicable for improving the efficiency and stability of the FASnI3‐based PSCs.
The OH…I− hydrogen bonding interactions between poly(vinyl alcohol) (PVA) and FASnI3 have the effects of introducing nucleation sites, slowing down crystal growth, directing the crystal orientation, reducing the trap states, and suppressing the migration of the ions. By adding PVA, the FASnI3–PVA perovskite solar cells attain improved power conversion efficiency and stability.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Topological photonics has been introduced as a powerful platform for integrated optics, since it can deal with robust light transport, and be further extended to the quantum world. Strikingly, ...valley-contrasting physics in topological photonic structures contributes to valley-related edge states, their unidirectional coupling, and even valley-dependent wave division in topological junctions. Here, we design and fabricate nanophotonic topological harpoon-shaped beam splitters (HSBSs) based on 120-deg-bending interfaces and demonstrate the first on-chip valley-dependent quantum information process. Two-photon quantum interference, namely, Hong-Ou-Mandel interference with a high visibility of 0.956±0.006, is realized with our 50/50 HSBS, which is constructed by two topologically distinct domain walls. Cascading this kind of HSBS together, we also demonstrate a simple quantum photonic circuit and generation of a path-entangled state. Our work shows that the photonic valley state can be used in quantum information processing, and it is possible to realize more complex quantum circuits with valley-dependent photonic topological insulators, which provides a novel method for on-chip quantum information processing.
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CMK, CTK, FMFMET, IJS, NUK, PNG, UL, UM
Based on the assumption that the dark energy possessing bulk viscosity is homogeneously and isotropically permeated in the universe, we propose three new viscous dark energy (VDE) models to ...characterize the accelerating universe. By constraining these three models with the latest cosmological observations, we find that they just deviate very slightly from the standard cosmological model and can alleviate effectively the current
H
0
tension between the local observation by the Hubble Space Telescope and the global measurement by the Planck Satellite. Interestingly, we conclude that a spatially flat universe in our VDE model with cosmic curvature is still supported by current data, and the scale invariant primordial power spectrum is strongly excluded at least at the
5.5
σ
confidence level in the three VDE models as the Planck result. We also give the
95
%
upper limits of the typical bulk viscosity parameter
η
in the three VDE scenarios.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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