The fundamental bandgap Eg of a semiconductor-often determined by means of optical spectroscopy-represents its characteristic fingerprint and changes distinctively with temperature. Here, we demonstrate that in magic sized II-VI clusters containing only 26 atoms, a pronounced weakening of the bonds occurs upon optical excitation, which results in a strong exciton-driven shift of the phonon spectrum. As a consequence, a drastic increase of dEg/dT (up to a factor of 2) with respect to bulk material or nanocrystals of typical size is found. We are able to describe our experimental data with excellent quantitative agreement from first principles deriving the bandgap shift with temperature as the vibrational entropy contribution to the free energy difference between the ground and optically excited states. Our work demonstrates how in small nanoparticles, photons as the probe medium affect the bandgap-a fundamental semiconductor property.Strategies for eradicating cancer stem cells (CSCs) are urgently required because CSCs are resistant to anticancer drugs and cause treatment failure, relapse and metastasis. https://www.selleckchem.com/products/acy-775.html Here, we show that photoactive functional nanocarbon complexes exhibit unique characteristics, such as homogeneous particle morphology, high water dispersibility, powerful photothermal conversion, rapid photoresponsivity and excellent photothermal stability. In addition, the present biologically permeable second near-infrared (NIR-II) light-induced nanocomplexes photo-thermally trigger calcium influx into target cells overexpressing the transient receptor potential vanilloid family type 2 (TRPV2). This combination of nanomaterial design and genetic engineering effectively eliminates cancer cells and suppresses stemness of cancer cells in vitro and in vivo. Finally, in molecular analyses of mechanisms, we show that inhibition of cancer stemness involves calcium-mediated dysregulation of the Wnt/β-catenin signalling pathway. The present technological concept may lead to innovative therapies to address the global issue of refractory cancers.Macropinocytosis is essential for myeloid cells to survey their environment and for growth of RAS-transformed cancer cells. Several growth factors and inflammatory stimuli are known to induce macropinocytosis, but its endogenous inhibitors have remained elusive. Stimulation of Roundabout receptors by Slit ligands inhibits directional migration of many cell types, including immune cells and cancer cells. We report that SLIT2 inhibits macropinocytosis in vitro and in vivo by inducing cytoskeletal changes in macrophages. In mice, SLIT2 attenuates the uptake of muramyl dipeptide, thereby preventing NOD2-dependent activation of NF-κB and consequent secretion of pro-inflammatory chemokine, CXCL1. Conversely, blocking the action of endogenous SLIT2 enhances CXCL1 secretion. SLIT2 also inhibits macropinocytosis in RAS-transformed cancer cells, thereby decreasing their survival in nutrient-deficient conditions which resemble tumor microenvironment. Our results identify SLIT2 as a physiological inhibitor of macropinocytosis and challenge the conventional notion that signals that enhance macropinocytosis negatively regulate cell migration, and vice versa.An amendment to this paper has been published and can be accessed via a link at the top of the paper.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.Precise genome editing using CRISPR-Cas9 is a promising therapeutic avenue for genetic diseases, although off-target editing remains a significant safety concern. Guide RNAs shorter than 16 nucleotides in length effectively recruit Cas9 to complementary sites in the genome but do not permit Cas9 nuclease activity. Here we describe CRISPR Guide RNA Assisted Reduction of Damage (CRISPR GUARD) as a method for protecting off-targets sites by co-delivery of short guide RNAs directed against off-target loci by competition with the on-target guide RNA. CRISPR GUARD reduces off-target mutagenesis while retaining on-target editing efficiencies with Cas9 and base editor. However, we discover that short guide RNAs can also support base editing if they contain cytosines within the deaminase activity window. We explore design rules and the universality of this method through in vitro studies and high-throughput screening, revealing CRISPR GUARD as a rapidly implementable strategy to improve the specificity of genome editing for most genomic loci. Finally, we create an online tool for CRISPR GUARD design.Kilonovae produced by the coalescence of compact binaries with at least one neutron star are promising standard sirens for an independent measurement of the Hubble constant (H0). Through their detection via follow-up of gravitational-wave (GW), short gamma-ray bursts (sGRBs) or optical surveys, a large sample of kilonovae (even without GW data) can be used for H0 contraints. Here, we show measurement of H0 using light curves associated with four sGRBs, assuming these are attributable to kilonovae, combined with GW170817. Including a systematic uncertainty on the models that is as large as the statistical ones, we find [Formula see text] and [Formula see text] for two different kilonova models that are consistent with the local and inverse-distance ladder measurements. For a given model, this measurement is about a factor of 2-3 more precise than the standard-siren measurement for GW170817 using only GWs.