Wide field-of-hearing metalens for aberration-free sound capture.

Metalenses are instruments that manipulate waves and have exhibited remarkable capabilities to date. However, an important hurdle arises due to the severe hampering of the angular response originating from coma and field curvature aberrations, which result in a loss of focusing ability. Herein, we provide a blueprint by introducing the notion of a wide field-of-hearing (FOH) metalens, designed particularly for capturing and focusing sound with decreased aberrations. Employing an aberration-free planar-thin metalens that leverages perfect acoustic symmetry conversion, we experimentally realize a robust wide FOH capability of approximately 140∘ in angular range. Moreover, our metalens features a relatively short focal length, enabling compact implementation by reducing the aperture-to-hearing plane distance. This is beneficial for space-efficient source-tracking sound sensing. Our strategy can be used across various platforms, potentially including energy harvesting, monitoring, imaging, and communication in auditory, ultrasonic, and submerged environments.

Regional bias of tumor suppressor gene mutations of STARD8 and WNK2 in colon cancers.

StAR-related lipid transfer domain protein 8 (STARD8), encoding a Rho-GTPase-activating protein, and WNK2, encoding a serine/threonine kinase are candidate tumor suppressor genes (TSGs) in human cancers. Inactivation of these genes that would promote cancer pathogenesis is largely unknown in colon cancer (CC). Our study addressed to address whether STARD8 and WNK2 genes are mutated in CC. STARD8 and WNK2 genes possess mononucleotide repeats in their exons, which could be the targets for frameshift mutations in cancers with high microsatellite instability (MSI-H). By single-strand conformation polymorphism (SSCP) analysis, we analyzed the repeated sequences in 140 CCs (95 CCs with MSI-H and 45 CCs with stable MSI (MSS)). By DNA sequencing, we found that five MSI-H CCs (5/95: 5.3%) harbored the frameshift mutations, whereas MSS CCs (0/45) did not. In addition, we detected regional heterogeneous frameshift mutations of these genes in four (25%) of 16 MSI-H CCs. In immunohistochemistry for WNK2, WNK2 expression in the MSI-H CCs was significantly lower than that in the MSS CCs. Our results for the mutation and expression indicate that STARD8 and WNK2 genes are altered at various levels (frameshift mutation, expression, and regional heterogeneity) in MSI-H CCs, which might play a role in the pathogenesis by inactivating their TSG functions.

Single-cell profiling identifies distinct hormonal, immunologic, and inflammatory signatures of endometriosis-constituting cells.

Endometriosis consists of ectopic endometrial epithelial cells (EEECs) and ectopic endometrial stromal cells (EESCs) mixed with heterogeneous stromal cells. To address how endometriosis-constituting cells are different from normal endometrium and among endometriosis subtypes and how their molecular signatures are related to phenotypic manifestations, we analyzed ovarian endometrial cyst (OEC), superficial peritoneal endometriosis (SPE), and deep infiltrating endometriosis (DIE) from 12 patients using single-cell RNA-sequencing (scRNA-seq). We identified 11 cell clusters, including EEEC, EESC, fibroblasts, inflammatory/immune, endothelial, mesothelial, and Schwann cells. For hormonal signatures, EESCs, but not EEECs, showed high estrogen signatures (estrogen response scores and HOXA downregulation) and low progesterone signatures (DKK1 downregulation) compared to normal endometrium. In EEECs, we found MUC5B+ TFF3low cells enriched in endometriosis. In lymphoid cells, evidence for both immune activation (high cytotoxicity in NK) and exhaustion (high checkpoint genes in NKT and cytotoxic T) was identified in endometriosis. Signatures and subpopulations of macrophages were remarkably different among endometriosis subtypes with increased monocyte-derived macrophages and IL1B expression in DIE. The scRNA-seq predicted NRG1 (macrophage)-ERBB3 (Schwann cell) interaction in endometriosis, expressions of which were validated by immunohistochemistry. Myofibroblast subpopulations differed according to the location (OECs from fibroblasts and SPE/DIEs from mesothelial cells and fibroblasts). Endometriosis endothelial cells displayed proinflammation, angiogenesis, and leaky permeability signatures that were enhanced in DIE. Collectively, our study revealed that (1) many cell types-endometrial, lymphoid, macrophage, fibroblast, and endothelial cells-are altered in endometriosis; (2) endometriosis cells show estrogen responsiveness, immunologic cytotoxicity and exhaustion, and proinflammation signatures that are different in endometriosis subtypes; and (3) novel endometriosis-specific findings of MUC5B+ EEECs, mesothelial cell-derived myofibroblasts, and NRG1-ERBB3 interaction may underlie the pathogenesis of endometriosis. Our results may help extend pathologic insights, dissect aggressive diseases, and discover therapeutic targets in endometriosis. © 2023 The Pathological Society of Great Britain and Ireland.

Leprosy-specific subsets of macrophages and Schwann cells identified by single-cell RNA-sequencing.

In Mycobacterium leprae (M. leprae)-infection, inflammatory cells' subsets and dynamics as well as the interactions with Schwann cells have remained elusive. We investigated individual cells in M. leprae-inoculated nude mice by single-cell RNA-sequencing (scRNA-seq). For macrophages, we dissected two M1-like subsets and five M2-like subsets, where lipid-associated signatures were pervasive in both M1-like and M2-like subsets. There were four macrophage trajectories showing: (i) pro-inflammatory (M1), (ii) lipid metabolism-related (M2), (iii) anti-inflammatory (M2), and (iv) interferon-stimulated gene-related (M2) fates. They displayed early divergence without ever rejoining along the paths, suggesting simultaneous or continuous stimuli for macrophage activation in leprosy. The scRNA-seq predicted Schwann cell-macrophage interactions (Notch1-Jag1, Plxnb1-Sema4d interactions). An immature Schwann cell subset showing Tfap2a expression was identified, indicating Schwann cell dedifferentiation in leprosy tissues. Expressions of Notch1, Jag1, Plxnb1, Sema4d, and Tfap2a were validated in mouse or human leprosy tissues by immunohistochemistry. We identified both pro-inflammatory and inflammation-resolution signatures, where lipid-associated signatures were pervasive to the macrophages, representing leprosy-specific macrophage states for prolonged and repeated episodes of inflammation and resolution. Our study identified refined molecular states and interactions of macrophages and Schwann cells, suggesting novel insights into the pathogenesis of unhealed inflammation with neuropathy and potential therapeutic targets for leprosy.

Recent advancements of metalenses for functional imaging.

Metasurfaces can modulate light with periodically arranged subwavelength scatterers, and they can generate arbitrary wavefronts. Therefore, they can be used to realize various optical components. In particular, metasurfaces can be used to realize lenses, so-called metalenses. In the last decade, metalenses have been actively studied and developed. In this review, we firstly introduce the fundamental principles of metalenses in terms of materials, phase modulation method, and design method. Based on these principles, the functionalities and the applications can consequently be realized. Metalenses have a much larger number of degrees of freedom compared with that of existing refractive or diffractive lenses. Thus, they afford functionalities such as tunability, high numerical aperture, and aberration correction. Metalenses with these functionalities can be applied in various optical systems such as imaging systems and spectrometers. Finally, we discuss the future applications of metalenses.

Scalable manufacturing of high-index atomic layer-polymer hybrid metasurfaces for metaphotonics in the visible.

Metalenses are attractive alternatives to conventional bulky refractive lenses owing to their superior light-modulating performance and sub-micrometre-scale thicknesses; however, limitations in existing fabrication techniques, including high cost, low throughput and small patterning area, have hindered their mass production. Here we demonstrate low-cost and high-throughput mass production of large-aperture visible metalenses using deep-ultraviolet argon fluoride immersion lithography and wafer-scale nanoimprint lithography. Once a 12″ master stamp is imprinted, hundreds of centimetre-scale metalenses can be fabricated using a thinly coated high-index film to enhance light confinement, resulting in a substantial increase in conversion efficiency. As a proof of concept, an ultrathin virtual reality device created with the printed metalens demonstrates its potential towards the scalable manufacturing of metaphotonic devices.

Concurrent inactivating mutations and expression losses of RGS2, HNF1A, and CAPN12 candidate tumor suppressor genes in colon cancers.

Microsatellite instability-high (MSI-H) colorectal cancer (CRC) is different from microsatellite stable (MSS) CRC concerning biological, and clinical features. In MSI-H CRCs, defects of mismatch repair genes produce increased mutation accumulation in repetitive DNA sequences. To see whether candidate tumor suppressor genes (TSGs) are altered in MSI-H CRC, we studied frameshift mutation and protein expression of candidate TSGs of RGS2, HNF1A, HNF1B, CAPN12, RCBTB2, ATE1, PKNOX1, and USP19. We found frameshift mutations of RGS2 in 5 (5%), HNF1A in 6 (6%), HNF1B in 2 (2%), CAPN12 in 3 (3%), RCBTB2 in 4 (4%), ATE1 in 2 (2%), PKNOX1 in 2 (2%), and USP19 in 2 (2%) MSI-H CRCs. However, we found no such mutations in MSS CRCs. RCBTB2, CAPN12, HNF1A, and HNF1B frameshift mutations revealed the regional difference in the same tumors. In addition, we identified loss of RGS2, HNF1A, and CAPN12 protein expression irrespective of MSI phenotype in 13-29% of CRCs. The results indicate that many TSGs harbor concurrent inactivating mutations and protein loss in MSI-H CRCs with intratumoral mutational heterogeneity, and that MSS CRCs are altered by protein losses. These alterations could contribute to CRC development and underlying mechanisms and consequences of the TSG alterations remain to be clarified.

Metasurface-driven full-space structured light for three-dimensional imaging.

Structured light (SL)-based depth-sensing technology illuminates the objects with an array of dots, and backscattered light is monitored to extract three-dimensional information. Conventionally, diffractive optical elements have been used to form laser dot array, however, the field-of-view (FOV) and diffraction efficiency are limited due to their micron-scale pixel size. Here, we propose a metasurface-enhanced SL-based depth-sensing platform that scatters high-density ~10 K dot array over the 180° FOV by manipulating light at subwavelength-scale. As a proof-of-concept, we place face masks one on the beam axis and the other 50° apart from axis within distance of 1 m and estimate the depth information using a stereo matching algorithm. Furthermore, we demonstrate the replication of the metasurface using the nanoparticle-embedded-resin (nano-PER) imprinting method which enables high-throughput manufacturing of the metasurfaces on any arbitrary substrates. Such a full-space diffractive metasurface may afford ultra-compact depth perception platform for face recognition and automotive robot vision applications.

Different Molecular Features of Epithelioid and Giant Cells in Foreign Body Reaction Identified by Single-Cell RNA Sequencing.

Although macrophage‒epithelioid cell (EPC)‒giant cell (GC) differentiation is acknowledged in foreign body reaction (FBR), the exact molecular features remain elusive. To discover the molecular profiles of EPC and GC, we analyzed mouse sponge and silk FBRs by integrating single-cell RNA sequencing and spatial sequencing, which identified seven cell types, including macrophages and fibroblasts. Macrophages comprised three subsets with a trajectory from M2-like cell to EPC to GC. They were different in many aspects, including cytokine, extracellular matrix organization/degradation, epithelial modules, and glycolysis that were consistent in both sponge and silk FBRs. EPCs exhibited epithelial modules and extracellular matrix organization, and GCs showed glycolysis, extracellular matrix degradation, and cell fusion signatures. Cellular interactions in GCs and M2-like cells were predicted to be higher than that in EPCs. High expression of inflammation or fusion-related (GPNMB, matrix metalloproteinase 12 gene MMP12, DCSTAMP) and glycolysis-related (PGAM1, ALDOA) genes was identified in GCs of human/mouse tissues, suggesting them as GC-specific markers. Our study identified unique signatures of EPCs and GCs in FBR. Importantly, GCs showed strong glycolysis signatures and cellular interactions, suggesting their activation in FBR. Our data on EPC and GC refinement and GC-specific markers enable the understanding of FBR and help to explore preventive and therapeutic management strategies for skin FBRs.

Mutational Alterations of DNA Methylation-related Genes CTCF, ZFP57, and ATF7IP Genes in Colon Cancers.

Deregulations of DNA-methylation-related genes are common in cancers, but frameshift mutation status in colon cancer (CC) is unknown. Our study aims to assess whether CTCF, ZFP57, and ATF7IP genes in this category are mutated in CC. CTCF, ZFP57, and ATF7IP genes have repeat coding sequences, which are frequently deleted or duplicated in CC, harboring the phenotype of unstable or high microsatellite instability (MSI-H). We studied 140 CCs [95 MSI-H CCs and 45 stable MSI (MSS) CCs], and found 7 CCs with MSI-H (6/95: 6.3%) harbored frameshift mutations within the repeats, whereas those with MSS did not. Of note, the CTCF frameshift mutations showed the regional difference in the 2 (12.5%) of 16 MSI-H CCs, indicating there was intratumoral heterogeneity. In the immunohistochemistry for ATF7IP, the MSI-H CC showed low intensity compared to MSS CC. Together, CTCF, ZFP57, and ATF7IP genes, despite the low incidence of the mutations, are altered in several ways (mutation, expression, and intratumoral heterogeneity) and could contribute to MSI-H CC development.

Asymmetric Diffraction in Plasmonic Meta-Gratings Using an IT-Shaped Nanoslit Array.

Diffraction is a fundamental phenomenon that reveals the wave nature of light. When a plane wave is transmitted or reflected from a grating or other periodic structures, diffracted light waves propagate at several angles that are specified by the period of the given structure. When the optical period is shorter than the wavelength, constructive interference of diffracted light rays from the subwavelength-scale grating forms a uniform plane wave. Many studies have shown that through the appropriate design of meta-atom geometry, metasurfaces can be used to control light properties. However, most semitransparent metasurfaces are designed to perform symmetric operation with regard to diffraction, meaning that light diffraction occurs identically for front- and back-side illumination. We propose a simple single-layer plasmonic metasurface that achieves asymmetric diffraction by optimizing the transmission phase from two types of nanoslits with I- and T-shaped structures. As the proposed structure is designed to have a different effective period for each observation side, it is either diffractive or nondiffractive depending on the direction of observation. The designed structure exhibits a diffraction angle of 54°, which can be further tuned by applying different period conditions. We expect the proposed asymmetric diffraction meta-grating to have great potential for the miniaturized optical diffraction control systems in the infrared band and compact optical diffraction filters for integrated optics.

Somatic Mutation of NLRP Genes in Gastric and Colonic Cancers.

Nucleotide-binding and leucine-rich repeat protein (NLRP) genes are involved in inflammasome formation that plays a role in inflammation/host defense and cell death. Both cell death and inflammation are crucial for cancer development, but the roles of NLRPs in cancer are partially known. In this study, we analyzed mononucleotide repeats in coding sequences of NLRP1, NLRP2, NLRP4 and NLRP9, and found 1, 1, 1 and 8 frameshift mutation (s) in gastric (GC) and colonic cancers (CRC), respectively. Five of the 32 high microsatellite instability (MSI-H) GCs (15.5%) and 6 of 113 MSI-H CRCs (5.5%) exhibited the frameshift mutations. There was no NLRP frameshift mutations in microsatellite stable (MSS) GCs and CRCs. We also discovered that 2 of 16 CRCs (12.5%) harbored intratumoral heterogeneity (ITH) of the NLRP9 frameshift mutations in one or more areas. In both GC and CRC with MSI-H, NLRP9 expression in NLRP9-mutated cases was significantly lower than that in NLRP9-non-mutated cases. Our data indicate that NLRP9 is altered at multiple levels (frameshift mutation, mutational ITH and loss of expression), which together could contribute to pathogenesis of MSI-H GC and CRC.

Brief Research Report Regional Difference in TRAF2 and TRAF3 Gene Mutations in Colon Cancers.

TRAF2 and TRAF3 genes of tumor necrosis factor receptor (TNF-R)-associated factor (TRAF) family are involved in diverse cell signaling, and function as both tumor suppressor gene and oncogene. Alterations of TRAF2 and TRAF3 in colon cancer (CC) along with their regional difference and microsatellite instability (MSI) are largely unknown. In the present study, we analyzed TRAF2 and TRAF3 frameshift mutations in 168 sporadic CCs (100 high MSI (MSI-H) and 68 microsatellite-stable (MSS) CCs). We identified TRAF2 and TRAF3 frameshift mutations in 4 (4%) and 3 CCs (3%) with MSI-H, respectively, but none in 68 cases of MSS CCs. Of the 168 CCs, we analyzed the mutations in multi-regions for 39 CCs (16 MSI-H and 23 MSS CCs), and discovered that 12.5% (2/16) and 6.3% (1/16) of MSI-H CCs exhibited regional difference in TRAF2 and TRAF3 mutations, respectively. In the multi-region samples of 23 MSS CCs, neither TRAF2 nor TRAF3 frameshift mutation was found. In 40% of CCs, both TRAF2 and TRAF3 expressions were increased compared to normal colon cells. Our data indicate that TRAF2 and TRAF3 frameshift mutations and their regional difference as well as altered expressions are present in MSI-H CCs, which could contribute to MSI-H cancer development.

Expression and Mutation Alterations of ZMYM4 Gene in Gastric and Colonic Cancers.

ZMYM4 is a zinc finger protein, whose cancer-related functions are partially known (cell shape maintenance and cell death). In this study, we analyzed 4 sites of mononucleotide repeats in the coding sequence of ZMYM4 in gastric (GC) and colonic cancers (CC). Seven of the 32 high microsatellite instability (MSI-H) GCs (21.9%) and 23 of 113 MSI-H CCs (20.4%) harbored ZMYM4 frameshift mutations with no significant difference between the 2 organs (P>0.05). There was no ZMYM4 frameshift mutations in microsatellite-stable GCs and CCs. We also identified that 6 of 16 MSI-H CCs (37.5%) exhibited intratumoral heterogeneity of the ZMYM4 frameshift mutations. In both GC and CC with MSI-H, ZMYM4 expression in ZMYM4-mutated cases was significantly lower than that in ZMYM4-nonmutated cases. Our study indicates that ZMYM4 is altered at multiple levels (frameshift mutation, mutational intratumoral heterogeneity, and loss of expression), suggesting their relations with MSI-H GC and CC.

Mutation and expression alterations of histone methylation-related NSD2, KDM2B and SETMAR genes in colon cancers.

Epigenetic dysregulation is a hallmark of cancers, and examples of its cancer-associated expression and mutation alterations are rapidly growing. Histone methylation, a process by which methyl groups are transferred to amino acids of histone proteins, is crucial for the epigenetic gene regulation. NSD2 (nuclear receptor-binding SET domain protein 2) and SETMAR are epigenetic regulators for histone methylation. KDM2B, also known as FBXL10, is a histone demethylase that targets histone methylation processes. They are known to be altered in many cancers, but somatic frameshift mutation and expression of these genes remain undetermined in many other subsets of cancers, including high microsatellite instability (MSI-H) colon cancer (CC). In this study, we analyzed mononucleotide repeats in coding sequences of NSD2, KDM2B and SETMAR genes, and found frameshift mutations in 10 %, 2 % and 1 % of CCs with MSI-H, respectively. Of note, there was no frameshift mutation of these genes in microsatellite stable (MSS) CCs. In addition, we discovered that 2 and 2 of 16 CRCs (12.5 % and 12.5 %) harbored intratumoral heterogeneity (ITH) of the NSD2 and KDM2B frameshift mutations, respectively. In the immunohistochemistry for NSD2, intensity of NSD2 immunostaining in MSI-H CC is decreased compared to that in MSS. These results suggest that NSD2 might be altered at multiple levels (frameshift mutation, mutational ITH and expression) in MSI-H CCs, and could be related to MSI-H cancer pathogenesis.

Cancer-related SRCAP and TPR mutations in colon cancers.

Current information suggests that SRCAP, TPR and CEACAM5 genes have cancer-related activities, but their alteration status is not well identified in colon cancer (CC). In this study, we analyzed frameshift mutations of these genes in CCs according to the microsatellite instability (MSI) status (high MSI (MSI-H) and microsatellite stable (MSS) CCs). In addition, regional difference in frameshift mutations of SRCAP, TPR and CEACAM5 genes were studied in CCs. In this study, we detected frameshift mutations (deletion or duplication of one or two bases) of SRCAP in 12 (12 %), TPR in 3 (3%) and CEACAM5 in 2 (2%) CCs with MSI-H. However, there was no such mutations in MSS cancers (P < 0.001). 18.8 % and 6.3 % of 16 CCs showed the regional difference in the SRCAP and TPR mutations, respectively. Approximately in 60 % of the CCs, SRCAP expression was increased compared to normal colon cells. Our study shows that SRCAP, TPR and CEACAM5 frameshift mutations and their regional difference as well as altered SRCAP expression are present in MSI-H CCs, which could contribute to CC development with MSI-H.

Recent Progress on Ultrathin Metalenses for Flat Optics.

As technology advances, electrical devices such as smartphones have become more and more compact, leading to a demand for the continuous miniaturization of optical components. Metalenses, ultrathin flat optical elements composed of metasurfaces consisting of arrays of subwavelength optical antennas, provide a method of meeting those requirements. Moreover, metalenses have many other distinctive advantages including aberration correction, active tunability, and semi-transparency, compared to their conventional refractive and diffractive counterparts. Therefore, over the last decade, great effort has been focused on developing metalenses to investigate and broaden the capabilities of metalenses for integration into future applications. Here, we discuss recent progress on metalenses including their basic design principles and notable characteristics such as aberration correction, tunability, and multifunctionality.

Multipole decomposition for interactions between structured optical fields and meta-atoms.

Interactions between structured optical fields (SOFs) and meta-atoms have been intensively studied, and stimulated by recent advancements on the generation of SOFs and on the synthesis of exotic meta-atoms. Multipole expansion is an efficient and accurate theoretical framework for studying such problems. In this work, explicit expressions of SOFs and their beam-shape coefficients are provided, and their properties are also briefly discussed; the considered SOFs include Laguerre-Gaussian (LG) beams, tightly-focused LG beams, Bessel beams, and cylindrical vector beams. Using the multipole expansion, selective excitations of multipolar resonances of a sphere is discussed. In addition, angular momentum dichroisms of a chiral sphere and an anisotropically chiral meta-atom are calculated to demonstrate selective excitation of multipoles with the desired order, parity, and orientation using engineered SOFs with angular momentum.

Compensation of spin-orbit interaction using the geometric phase of distributed nanoslits for polarization-independent plasmonic vortex generation.

A metasurface is a planar optical device that controls the phase, amplitude, and polarization of light through subwavelength-scale unit elements, called meta-atom. The tunability of plasmonic vortex lens (PVL) which generates surface plasmon polaritons (SPPs) carrying orbital angular momentum can be improved by using meta-atom. However, conventional PVLs exhibit nonuniform field profiles according to the incident polarization states owing to the spin-orbital interaction (SOI) effect observed during SPP excitation. This paper describes a method of compensating for SOI of PVL by using the geometric phase of distributed nanoslits in a gold film. By designing the orientation angles of slit pairs, the anti-phase of the SOI effect can be generated for compensatory effect. In addition, polarization-independent PVLs are designed by applying a detour phase based on the position of the slit pairs. PVLs for center-, off-center-, and multiple-focus cases are demonstrated and measured via a near-field scanning microscope.

Lotus (Nelumbo nucifera) seed protein isolate exerts anti-inflammatory and antioxidant effects in LPS-stimulated RAW264.7 macrophages via inhibiting NF-κB and MAPK pathways, and upregulating catalase activity.

Lotus seed has long been used in traditional medicine and cuisine. In this study, lotus seed protein (LSP) was isolated and evaluated its anti-inflammatory effect in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. LSP isolate (LSPI) treatment in LPS-stimulated RAW264.7 macrophages resulted in the significant (p < 0.05) decrease of NO production by downregulation of the expressions of mRNA and protein, including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). In addition, LSPI treatment attenuated the production of reactive oxygen species (ROS) through increasing catalase activity, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1ß in LPS-stimulated RAW264.7 macrophages. Furthermore, LPS stimulation in RAW264.7 macrophages caused the translocation of nuclear factor-kappa B (NF-κB) into the nucleus and the phosphorylation of mitogen-activated protein kinase (MAPK) but these stimulations were abolished by LSPI treatment.