Recent advances in endocrine organoids for therapeutic application.

The endocrine system, consisting of the hypothalamus, pituitary, endocrine glands, and hormones, plays a critical role in hormone metabolic interactions. The complexity of the endocrine system is a significant obstacle to understanding and treating endocrine disorders. Notably, advances in endocrine organoid generation allow a deeper understanding of the endocrine system by providing better comprehension of molecular mechanisms of pathogenesis. Here, we highlight recent advances in endocrine organoids for a wide range of therapeutic applications, from cell transplantation therapy to drug toxicity screening, combined with development in stem cell differentiation and gene editing technologies. In particular, we provide insights into the transplantation of endocrine organoids to reverse endocrine dysfunctions and progress in developing strategies for better engraftments. We also discuss the gap between preclinical and clinical research. Finally, we provide future perspectives for research on endocrine organoids for the development of more effective treatments for endocrine disorders.

Proteogenomic landscape of human pancreatic ductal adenocarcinoma in an Asian population reveals tumor cell-enriched and immune-rich subtypes.

We report a proteogenomic analysis of pancreatic ductal adenocarcinoma (PDAC). Mutation-phosphorylation correlations identified signaling pathways associated with somatic mutations in significantly mutated genes. Messenger RNA-protein abundance correlations revealed potential prognostic biomarkers correlated with patient survival. Integrated clustering of mRNA, protein and phosphorylation data identified six PDAC subtypes. Cellular pathways represented by mRNA and protein signatures, defining the subtypes and compositions of cell types in the subtypes, characterized them as classical progenitor (TS1), squamous (TS2-4), immunogenic progenitor (IS1) and exocrine-like (IS2) subtypes. Compared with the mRNA data, protein and phosphorylation data further classified the squamous subtypes into activated stroma-enriched (TS2), invasive (TS3) and invasive-proliferative (TS4) squamous subtypes. Orthotopic mouse PDAC models revealed a higher number of pro-tumorigenic immune cells in TS4, inhibiting T cell proliferation. Our proteogenomic analysis provides significantly mutated genes/biomarkers, cellular pathways and cell types as potential therapeutic targets to improve stratification of patients with PDAC.

PD-L1-directed PlGF/VEGF blockade synergizes with chemotherapy by targeting CD141+ cancer-associated fibroblasts in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a poor 5-year overall survival rate. Patients with PDAC display limited benefits after undergoing chemotherapy or immunotherapy modalities. Herein, we reveal that chemotherapy upregulates placental growth factor (PlGF), which directly activates cancer-associated fibroblasts (CAFs) to induce fibrosis-associated collagen deposition in PDAC. Patients with poor prognosis have high PIGF/VEGF expression and an increased number of PIGF/VEGF receptor-expressing CAFs, associated with enhanced collagen deposition. We also develop a multi-paratopic VEGF decoy receptor (Ate-Grab) by fusing the single-chain Fv of atezolizumab (anti-PD-L1) to VEGF-Grab to target PD-L1-expressing CAFs. Ate-Grab exerts anti-tumor and anti-fibrotic effects in PDAC models via the PD-L1-directed PlGF/VEGF blockade. Furthermore, Ate-Grab synergizes with gemcitabine by relieving desmoplasia. Single-cell RNA sequencing identifies that a CD141+ CAF population is reduced upon Ate-Grab and gemcitabine combination treatment. Overall, our results elucidate the mechanism underlying chemotherapy-induced fibrosis in PDAC and highlight a combinatorial therapeutic strategy for desmoplastic cancers.

Universal Metasurfaces for Complete Linear Control of Coherent Light Transmission.

Recent advances in metasurfaces and optical nanostructures have enabled complex control of incident light with optically thin devices. However, it has thus far been unclear whether it is possible to achieve complete linear control of coherent light transmission, that is, independent control of polarization, amplitude, and phase for both input polarization states, with just a single, thin nanostructure array. Here, it is proved possible, and a universal metasurface is proposed, a bilayer array of high-index elliptic cylinders that possesses a complete degree of optical freedom with fully designable chirality and anisotropy. The completeness of achievable light control is mathematically shown with corresponding Jones matrices, new types of 3D holographic schemes that were formerly impossible are experimentally demonstrated, and a systematic way of realizing any input-state-sensitive vector linear optical device is presented. The results unlock previously inaccessible degrees of freedom in light transmission control.

Directional radiation for optimal radiative cooling.

The omnidirectional radiation scheme has been widely applied to thermal emitters for radiative cooling. We quantitatively illustrate that significant net radiative absorption at high zenith angles limits the performance of such isotropic emitters, and demonstrate that simply cutting off components corresponding to high angles can substantially improve the cooling performance of commonly used isotropic emitter designs. We also present an expression for the ideal directional spectral emissivity at conditions below ambient temperature. As our approach can be applied to coolers with arbitrary surfaces, our results may serve as a basic guideline for designing practical systems with various surfaces, such as rooftops or façades of modern buildings with complicated geometries.

Ideal spectral emissivity for radiative cooling of earthbound objects.

We investigate the fundamental limit of radiative cooling of objects on the Earth's surfaces under general conditions including nonradiative heat transfer. We deduce the lowest steady-state temperature attainable and highest net radiative cooling power density available as a function of temperature. We present the exact spectral emissivity that can reach such limiting values, and show that the previously used 8-13 µm atmospheric window is highly inappropriate in low-temperature cases. The critical need for materials with simultaneously optimized optical and thermal properties is also identified. These results provide a reference against which radiative coolers can be benchmarked.

Near-atomically flat, chemically homogeneous, electrically conductive optical metasurface.

Metasurfaces, or two-dimensional arrays of subwavelength-scale structures, can exhibit extraordinary optical properties. However, typical metasurfaces have a bumpy surface morphology that may restrict their practical applications. Here, we propose and demonstrate an optical metasurface that is composed of a thin metallic film, with hidden dielectric structures underneath, and a metal back mirror layer. Exploiting the large difference between the Thomas-Fermi screening length for longitudinal electric fields and the skin depth for transverse electromagnetic fields, the near-atomically flat top surface of the proposed structure can appear homogeneous chemically and electrically but highly inhomogenous optically. The size and shape of the hidden dielectric structures as well as the thickness of the top metallic layer can be tailored to acquire desired optical properties. We performed both theoretical and experimental studies of the proposed metasurface, finding a good agreement between them. This work provides a new platform for ultra-flat optical devices, such as a wavelength selective electrode, diffusive back reflector, meta-lens, and plasmonically enhanced optical biosensors.

Bright and vivid plasmonic color filters having dual resonance modes with proper orthogonality.

The mode orthogonality fundamentally influences the scattering spectra of multi-resonance systems, such as plasmonic color filters. We show that planar arrays of silver nanostructures with dual localized surface plasmon resonances and the right mode orthogonality can function as transmissive RGB color filters with peak transmittances higher than 70%, and color gamut areas larger than 90% of the sRGB space. These are the brightest and most saturated of all designs proposed thus far. We present the Pareto frontier from designs with more than 80% peak transmittance, to designs that achieve a color gamut larger than 120% of the sRGB space.

Transferrable Plasmonic Au Thin Film Containing Sub-20 nm Nanohole Array Constructed via High-Resolution Polymer Self-Assembly and Nanotransfer Printing.

The fabrication and characterization of nanoscale hole arrays (NHA) have been extensively performed for a variety of unique characteristics including extraordinary optical transmission phenomenon observed for plasmonic NHAs. Although the size miniaturization and hole densification are strongly required for enhancement of high-frequency optical responses, from a practical point-of-view, it is still not straightforward to manufacture NHA using conventional lithography techniques. Herein, a facile, cost-effective, and transferrable fabrication route for high-resolution and high-density NHA with sub-50 nm periodicity is demonstrated. Solvent-assisted nanotransfer printing with ultrahigh-resolution combined with block copolymer self-assembly is used to fabricate well-defined Si nanomesh master template with 4-fold symmetry. An Au NHA film on quartz substrate is then obtained by thermal-evaporation on the Si master and subsequent transfer of the sample, resulting in NHA structure having a hole with a diameter of 18 nm and a density over 400 holes/µm2. A resonance peak at the wavelength of 650 nm, which is not present in the transmittance spectrum of a flat Au film, is observed for the Au NHA film. Finite-difference time-domain (FDTD) simulation results propose that the unexpected peak appears because of plasmonic surface guiding mode. The position of the resonance peak shows the sensitivity toward the change of the refractive index of surrounding medium, suggesting it as a promising label-free sensor application. In addition, other types of Au nanostructure arrays such as geometry-controlled NHA and nanoparticle arrays (NPAs) shows the outstanding versatility of our approach.

Bimodal phase separated block copolymer/homopolymer blends self-assembly for hierarchical porous metal nanomesh electrodes.

Transparent conducting electrodes (TCEs) are essential components in various optoelectronic devices. Nanostructured metallic thin film is one of the promising candidates to complement current metal oxide films, such as ITO, where high cost rare earth elements have been a longstanding issue. Herein, we present that multiscale porous metal nanomesh thin films prepared by bimodal self-assembly of block copolymer (BCP)/homopolymer blends may offer a new opportunity for TCE. This hierarchical concurrent self-assembly consists of macrophase separation between BCP and homopolymer as well as microphase separation of BCP, and thus provides a straightforward spontaneous production of a highly porous multiscale pattern over an arbitrary large area. Employing a conventional pattern transfer process, we successfully demonstrated a multiscale highly porous metallic thin film with reasonable optical transparency, electro-conductance, and large-area uniformity, taking advantage of low loss light penetration through microscale pores and significant suppression of light reflection at the nanoporous structures. This well-defined controllable bimodal self-assembly can offer valuable opportunities for many different applications, including optoelectronics, energy harvesting, and membranes.