All-Glass 100 mm Diameter Visible Metalens for Imaging the Cosmos.

Metasurfaces, optics made from subwavelength-scale nanostructures, have been limited to millimeter-sizes by the scaling challenge of producing vast numbers of precisely engineered elements over a large area. In this study, we demonstrate an all-glass 100 mm diameter metasurface lens (metalens) comprising 18.7 billion nanostructures that operates in the visible spectrum with a fast f-number (f/1.5, NA = 0.32) using deep-ultraviolet (DUV) projection lithography. Our work overcomes the exposure area constraints of lithography tools and demonstrates that large metasurfaces are commercially feasible. Additionally, we investigate the impact of various fabrication errors on the imaging quality of the metalens, several of which are specific to such large area metasurfaces. We demonstrate direct astronomical imaging of the Sun, the Moon, and emission nebulae at visible wavelengths and validate the robustness of such metasurfaces under extreme environmental thermal swings for space applications.

SARS-CoV-2 produces a microRNA CoV2-miR-O8 in patients with COVID-19 infection.

Many viruses produce microRNAs (miRNAs), termed viral miRNAs (v-miRNAs), with the capacity to target host gene expression. Bioinformatic and cell culture studies suggest that SARS-CoV-2 can also generate v-miRNAs. This patient-based study defines the SARS-CoV-2 encoded small RNAs present in nasopharyngeal swabs of patients with COVID-19 infection using small RNA-seq. A specific conserved sequence (CoV2-miR-O8) is defined that is not expressed in other coronaviruses but is preserved in all SARS-CoV-2 variants. CoV2-miR-O8 is highly represented in nasopharyngeal samples from patients with COVID-19 infection, is detected by RT-PCR assays in patients, has features consistent with Dicer and Drosha generation as well as interaction with Argonaute and targets specific human microRNAs.

Kidney organoid models reveal cilium-autophagy metabolic axis as a therapeutic target for PKD both in vitro and in vivo.

Human pluripotent stem cell-derived kidney organoids offer unprecedented opportunities for studying polycystic kidney disease (PKD), which still has no effective cure. Here, we developed both in vitro and in vivo organoid models of PKD that manifested tubular injury and aberrant upregulation of renin-angiotensin aldosterone system. Single-cell analysis revealed that a myriad of metabolic changes occurred during cystogenesis, including defective autophagy. Experimental activation of autophagy via ATG5 overexpression or primary cilia ablation significantly inhibited cystogenesis in PKD kidney organoids. Employing the organoid xenograft model of PKD, which spontaneously developed tubular cysts, we demonstrate that minoxidil, a potent autophagy activator and an FDA-approved drug, effectively attenuated cyst formation in vivo. This in vivo organoid model of PKD will enhance our capability to discover novel disease mechanisms and validate candidate drugs for clinical translation.

Helicity and Polarization Gradient Optical Trapping in Evanescent Fields.

Optical traps using nonconservative forces instead of conservative intensity-gradient forces expand the trap parameter space. Existing traps with nonconservative helicity-dependent forces are limited to chiral particles and fields with helicity gradients. We relax these constraints by proposing helicity and polarization gradient optical trapping of achiral particles in evanescent fields. We further propose an optical switching system in which a microsphere is trapped and optically manipulated around a microfiber using polarization gradients. Our Letter deepens the understanding of light-matter interactions in polarization gradient fields and expands the range of compatible particles and stable trapping fields.

Food amyloid fibrils are safe nutrition ingredients based on in-vitro and in-vivo assessment.

Food protein amyloid fibrils have superior technological, nutritional, sensorial, and physical properties compared to native monomers, but there is as yet insufficient understanding of their digestive fate and safety for wide consumption. By combining SDS-PAGE, ELISA, fluorescence, AFM, MALDI-MS, CD, microfluidics, and SAXS techniques for the characterization of ß-lactoglobulin and lysozyme amyloid fibrils subjected to in-vitro gastrointestinal digestion, here we show that either no noticeable conformational differences exist between amyloid aggregates and their monomer counterparts after the gastrointestinal digestion process (as in ß-lactoglobulin), or that amyloid fibrils are digested significantly better than monomers (as in lysozyme). Moreover, in-vitro exposure of human cell lines and in-vivo studies with C. elegans and mouse models, indicate that the digested fibrils present no observable cytotoxicity, physiological abnormalities in health-span, nor accumulation of fibril-induced plaques in brain nor other organs. These extensive in-vitro and in-vivo studies together suggest that the digested food amyloids are at least equally as safe as those obtained from the digestion of corresponding native monomers, pointing to food amyloid fibrils as potential ingredients for human nutrition.

Renewable Energy from Livestock Waste Valorization: Amyloid-Based Feather Keratin Fuel Cells.

Increasing carbon emissions have accelerated climate change, resulting in devastating effects that are now tangible on an everyday basis. This is mirrored by a projected increase in global energy demand of approximately 50% within a single generation, urging a shift from fossil-fuel-derived materials toward greener materials and more sustainable manufacturing processes. Biobased industrial byproducts, such as side streams from the food industry, are attractive alternatives with strong potential for valorization due to their large volume, low cost, renewability, biodegradability, and intrinsic material properties. Here, we demonstrate the reutilization of industrial chicken feather waste into proton-conductive membranes for fuel cells, protonic transistors, and water-splitting devices. Keratin was isolated from chicken feathers via a fast and economical process, converted into amyloid fibrils through heat treatment, and further processed into membranes with an imparted proton conductivity of 6.3 mS cm-1 using a simple oxidative method. The functionality of the membranes is demonstrated by assembling them into a hydrogen fuel cell capable of generating 25 mW cm-2 of power density to operate various types of devices using hydrogen and air as fuel. Additionally, these membranes were used to generate hydrogen through water splitting and in protonic field-effect transistors as thin-film modulators of protonic conductivity via the electrostatic gating effect. We believe that by converting industrial waste into renewable energy materials at low cost and high scalability, our green manufacturing process can contribute to a fully circular economy with a neutral carbon footprint.

Topologically protected optical polarization singularities in four-dimensional space.

Optical singularities play a major role in modern optics and are frequently deployed in structured light, super-resolution microscopy, and holography. While phase singularities are uniquely defined as locations of undefined phase, polarization singularities studied thus far are either partial, i.e., bright points of well-defined polarization, or are unstable for small field perturbations. We demonstrate a complete, topologically protected polarization singularity; it is located in the four-dimensional space spanned by the three spatial dimensions and the wavelength and is created in the focus of a cascaded metasurface-lens system. The field Jacobian plays a key role in the design of such higher-dimensional singularities, which can be extended to multidimensional wave phenomena, and pave the way for unconventional applications in topological photonics and precision sensing.

Point singularity array with metasurfaces.

Phase singularities are loci of darkness surrounded by monochromatic light in a scalar field, with applications in optical trapping, super-resolution imaging, and structured light-matter interactions. Although 1D singular structures, like optical vortices, are common due to their robust topological properties, uncommon 0D (point) and 2D (sheet) singularities can be generated by wavefront-shaping devices like metasurfaces. With the design flexibility of metasurfaces, we deterministically position ten identical point singularities using a single illumination source. The phasefront is inverse-designed using phase-gradient maximization with an automatically-differentiable propagator and produces tight longitudinal intensity confinement. The array is experimentally realized with a TiO2 metasurface. One possible application is blue-detuned neutral atom trap arrays, for which this field would enforce 3D confinement and a potential depth around 0.22 mK per watt of incident laser power. We show that metasurface-enabled point singularity engineering may significantly simplify and miniaturize the optical architecture for super-resolution microscopes and dark traps.

Extreme ultraviolet metalens by vacuum guiding.

Extreme ultraviolet (EUV) radiation is a key technology for material science, attosecond metrology, and lithography. Here, we experimentally demonstrate metasurfaces as a superior way to focus EUV light. These devices exploit the fact that holes in a silicon membrane have a considerably larger refractive index than the surrounding material and efficiently vacuum-guide light with a wavelength of ~50 nanometers. This allows the transmission phase at the nanoscale to be controlled by the hole diameter. We fabricated an EUV metalens with a 10-millimeter focal length that supports numerical apertures of up to 0.05 and used it to focus ultrashort EUV light bursts generated by high-harmonic generation down to a 0.7-micrometer waist. Our approach introduces the vast light-shaping possibilities provided by dielectric metasurfaces to a spectral regime that lacks materials for transmissive optics.

Turning Food Protein Waste into Sustainable Technologies.

For each kilogram of food protein wasted, between 15 and 750 kg of CO2 end up in the atmosphere. With this alarming carbon footprint, food protein waste not only contributes to climate change but also significantly impacts other environmental boundaries, such as nitrogen and phosphorus cycles, global freshwater use, change in land composition, chemical pollution, and biodiversity loss. This contrasts sharply with both the high nutritional value of proteins, as well as their unique chemical and physical versatility, which enable their use in new materials and innovative technologies. In this review, we discuss how food protein waste can be efficiently valorized not only by reintroduction into the food chain supply but also as a template for the development of sustainable technologies by allowing it to exit the food-value chain, thus alleviating some of the most urgent global challenges. We showcase three technologies of immediate significance and environmental impact: biodegradable plastics, water purification, and renewable energy. We discuss, by carefully reviewing the current state of the art, how proteins extracted from food waste can be valorized into key players to facilitate these technologies. We furthermore support analysis of the extant literature by original life cycle assessment (LCA) examples run ad hoc on both plant and animal waste proteins in the context of the technologies considered, and against realistic benchmarks, to quantitatively demonstrate their efficacy and potential. We finally conclude the review with an outlook on how such a comprehensive management of food protein waste is anticipated to transform its carbon footprint from positive to negative and, more generally, have a favorable impact on several other important planetary boundaries.

All-Optical Tunability of Metalenses Permeated with Liquid Crystals.

Metasurfaces have been extensively engineered to produce a wide range of optical phenomena, allowing exceptional control over the propagation of light. However, they are generally designed as single-purpose devices without a modifiable postfabrication optical response, which can be a limitation to real-world applications. In this work, we report a nanostructured planar-fused silica metalens permeated with a nematic liquid crystal (NLC) and gold nanoparticle solution. The physical properties of embedded NLCs can be manipulated with the application of external stimuli, enabling reconfigurable optical metasurfaces. We report the all-optical, dynamic control of the metalens optical response resulting from thermoplasmonic-induced changes of the NLC solution associated with the nematic-isotropic phase transition. A continuous and reversible tuning of the metalens focal length is experimentally demonstrated, with a variation of 80 µm (0.16% of the 5 cm nominal focal length) along the optical axis. This is achieved without direct mechanical or electrical manipulation of the device. The reconfigurable properties are compared with corroborating numerical simulations of the focal length shift and exhibit close correspondence.

Knowledge, Attitudes, and Practices of COVID-19 Vaccination among Adults in Singapore: A Cross-Sectional Study.

Public health measures promoting compliance of COVID-19 vaccination requires understanding of knowledge, attitudes, and practices (KAP). This study explored the KAP and risk factors influencing COVID-19 vaccination, including changes in preventive practices before and after vaccination in a high-income country, Singapore. An online cross-sectional study among Singaporeans and permanent residents aged 21 years and older was conducted from July to August 2021. Univariate and multivariable logistic regressions using RStudio version 1.4.1106 was performed to assess associations between demographic factors, KAP, and vaccination status. P values < 0.05 were considered statistically significant. A total of 869 respondents completed the survey. Individuals with higher knowledge (adjusted odds ratio [aOR] = 2.00, P = 0.024), perceived efficacy (aOR = 1.19, P = 0.004), perceived safety (aOR = 1.20, P = 0.005), and willingness to uptake (aOR = 1.55, P < 0.001) scores were more likely to be vaccinated. There was a significant increase in the use of proper handwashing techniques among the vaccinated group before and after vaccinations. The governmental risk communication approaches have been useful in instilling high levels of vaccine knowledge. High levels of good attitudes about and knowledge of COVID-19 vaccination were associated with a high level of vaccination practices. Good perceived vaccine efficacy and confidence in government were also associated with positive vaccine uptake. This study paves the way for more targeted government measures to be implemented to improve vaccination rates of COVID-19 booster vaccines in a high-income country like Singapore.

Complete Sequences of the Velvet Worm Slime Proteins Reveal that Slime Formation is Enabled by Disulfide Bonds and Intrinsically Disordered Regions.

The slime of velvet worms (Onychophora) is a strong and fully biodegradable protein material, which upon ejection undergoes a fast liquid-to-solid transition to ensnare prey. However, the molecular mechanisms of slime self-assembly are still not well understood, notably because the primary structures of slime proteins are yet unknown. Combining transcriptomic and proteomic studies, the authors have obtained the complete primary sequences of slime proteins and identified key features for slime self-assembly. The high molecular weight slime proteins contain cysteine residues at the N- and C-termini that mediate the formation of multi-protein complexes via disulfide bonding. Low complexity domains in the N-termini are also identified and their propensity for liquid-liquid phase separation is established, which may play a central role in slime biofabrication. Using solid-state nuclear magnetic resonance, rigid and flexible domains of the slime proteins are mapped to specific peptide domains. The complete sequencing of major slime proteins is an important step toward sustainable fabrication of polymers inspired by the velvet worm slime.

Stereotactic radiosurgery for melanoma brain metastases: Concurrent immune checkpoint inhibitor therapy associated with superior clinicoradiological response outcomes.

INTRODUCTION/PURPOSE: This study assessed long-term clinical and radiological outcomes following treatment with combination stereotactic radiosurgery (SRS) and immunotherapy (IT) for melanoma brain metastases (BM). METHODS: A retrospective review was performed in a contemporary cohort of patients with melanoma BM at a single tertiary institution receiving Gamma Knife® SRS for melanoma BM. Multivariate Cox proportional-hazards modelling was performed with a P <0.05 for significance. RESULTS: 101 patients (435 melanoma BM) were treated with SRS between January-2015 and June-2019. 68.3% of patients received IT within 4 weeks of SRS (concurrent) and 31.7% received SRS alone or non-concurrently with IT. Overall, BM local control rate was 87.1% after SRS. Median progression free survival was 8.7 months. Median follow-up was 29.2 months. On multivariate analysis (MVA), patients receiving concurrent SRS-IT maintained a higher chance of achieving a complete (CR) or partial response (PR) [HR 2.6 (95% CI: 1.2-5.5, P = 0.012)] and a reduced likelihood of progression of disease (PD) [HR 0.52 (95% CI: 0.16-0.60), P = 0.048]. Any increase in BM volume on the initial MRI 3 months after SRS predicted a lower likelihood of achieving long-term CR or PR on MVA accounting for concurrent IT, BRAF status and dexamethasone use [HR = 0.048 (95% CI: 0.007-0.345, P = 0.0026)]. Stratified volumetric change demonstrated a sequential relationship with outcomes on Kaplan-Meier analysis. CONCLUSION: Concurrent SRS-IT has favourable clinical and radiological outcomes with respect to CR, PR and a reduced likelihood of PD. Changes in BM volume on the initial MRI 3 months after SRS were predictive of long-term outcomes for treatment response.

A High Aspect Ratio Inverse-Designed Holey Metalens.

Free-standing nanofins or pillar meta-atoms are the most common constituent building blocks in metalenses and metasurfaces in general. Here, we present an alternative metasurface geometry based on high aspect ratio via-holes. We design and characterize metalenses comprising ultradeep via-holes in 5 µm thick free-standing silicon membranes with hole aspect ratios approaching 30:1. These metalenses focus incident infrared light into a diffraction-limited spot. Instead of shaping the metasurface optical phase profile alone, we engineer both transmitted phase and amplitude profiles simultaneously by inverse-designing the lens effective index profile. This approach improves the impedance match between the incident and transmitted waves, thereby increasing the focusing efficiency. The holey platform increases the accessible aspect ratio of optical nanostructures without sacrificing mechanical robustness. The high nanostructure aspect ratio also increases the chromatic group delay range attainable, paving the way for a generation of high aspect ratio ruggedized flat optics, including large-area broadband achromatic metalenses.

Stereotactic ablative radiotherapy for hepatocellular carcinoma: A systematic review and meta-analysis of local control, survival and toxicity outcomes.

There is a growing body of literature supporting the use of stereotactic ablative body radiotherapy (SABR) in the management of primary hepatocellular carcinoma (HCC). This systematic review and meta-analysis of the current published evidence for SABR for HCC assessed the impact of treatment dose, fractionation and tumour size on the outcomes of local control (LC), overall survival (OS) and toxicity. A systematic search was independently performed by two authors for articles published in peer-reviewed journals between January 2005 and December 2019. A DerSimonian and Laird random effects model was used to assess pooled results. A multivariate meta-regression analysis incorporated the effect of explanatory variables (radiation dose in EQD2[10], fractionation and tumour size) on outcomes of OS, LC and toxicity. Forty-nine cohorts involving 2846 HCC patients with 3088 lesions treated with SABR were included. Pooled 1-, 2- and 3-year LC rates were 91.1% (95% confidence interval [CI] 88.3-93.2), 86.7% (95% CI 82.7-89.8) and 84.2% (95% CI 77.9-88.9) respectively. Pooled 1-, 2- and 3-year OS rates were 78.4% (95% CI 73.4-82.6), 61.3% (55.2-66.9) and 48.3% (95% CI 39.0-57). Population-weighted median grade 3 toxicity rates were 6.5% (IQR 3.2-16) and mean grade 4/5 rates were 1.4% (IQR 0-2.1). Within EQD2[10] ranges of 40 to 83.33 Gy corresponding to common dose-fractionation regimens of 30-50 Gy in 5 fractions, there was a multivariate association between superior LC and OS with increasing EQD2[10] , with a proportionately smaller increase in grade 3 toxicity and no association with grade 4/5 toxicity. Stereotactic ablative body radiotherapy is a viable treatment option for HCC with high LC rates and low rates of reported grade 3/4 toxicity. Increasing EQD2[10] was associated with improvements in LC and OS with a comparatively smaller increase in toxicity. Prospective randomised trials are warranted to define optimal patient selection and dose-fractionation regimens.

Engineering phase and polarization singularity sheets.

Optical phase singularities are zeros of a scalar light field. The most systematically studied class of singular fields is vortices: beams with helical wavefronts and a linear (1D) singularity along the optical axis. Beyond these common and stable 1D topologies, we show that a broader family of zero-dimensional (point) and two-dimensional (sheet) singularities can be engineered. We realize sheet singularities by maximizing the field phase gradient at the desired positions. These sheets, owning to their precise alignment requirements, would otherwise only be observed in rare scenarios with high symmetry. Furthermore, by applying an analogous procedure to the full vectorial electric field, we can engineer paraxial transverse polarization singularity sheets. As validation, we experimentally realize phase and polarization singularity sheets with heart-shaped cross-sections using metasurfaces. Singularity engineering of the dark enables new degrees of freedom for light-matter interaction and can inspire similar field topologies beyond optics, from electron beams to acoustics.

Molecular detection of pathogens from ectoparasites recovered from peri-domestic animals, and the first description of a Candidatus Midichloria sp. from Haemaphysalis wellingtoni from rural communities in Malaysia.

Rural communities in Malaysia have been shown to be exposed to Coxiella, Borrelia and rickettsial infections in previous seroprevalence studies. Further research is necessary to identify the actual causative agents and the potential vectors of these infections. The arthropods parasitizing peri-domestic animals in these communities may serve as the vector in transmitting arthropod-borne and zoonotic agents to the humans. Molecular screening of bacterial and zoonotic pathogens from ticks and fleas collected from dogs, cats and chickens from six rural communities in Malaysia was undertaken. These communities were made up of mainly the indigenous people of Malaysia, known as the Orang Asli, as well as settlers in oil palm plantations. The presence of Coxiella burnetii, Borrelia, and rickettsial agents, including Rickettsia and Anaplasma, was investigated by performing polymerase chain reaction (PCR) and DNA sequencing. Candidatus Rickettsia senegalensis was detected in one out of eight pools of Ctenocephalides felis fleas. A relapsing fever group Borrelia sp. was identified from one of seven Haemaphysalis hystricis ticks tested. The results from the PCR screening for Anaplasma unexpectedly revealed the presence of Candidatus Midichloria sp., a potential tick endosymbiont, in two out of fourteen Haemaphysalis wellingtoni ticks tested. C. burnetii was not detected in any of the samples tested. The findings here provide evidence for the presence of potentially novel strains of rickettsial and borrelial agents in which their impact on public health risks among the rural communities in Malaysia merit further investigation. The detection of a potential endosymbiont of ticks also suggest that the presence of tick endosymbionts in the region is not fully explored.

An integrative model of pathway convergence in genetically heterogeneous blast crisis chronic myeloid leukemia.

Targeted therapies against the BCR-ABL1 kinase have revolutionized treatment of chronic phase (CP) chronic myeloid leukemia (CML). In contrast, management of blast crisis (BC) CML remains challenging because BC cells acquire complex molecular alterations that confer stemness features to progenitor populations and resistance to BCR-ABL1 tyrosine kinase inhibitors. Comprehensive models of BC transformation have proved elusive because of the rarity and genetic heterogeneity of BC, but are important for developing biomarkers predicting BC progression and effective therapies. To better understand BC, we performed an integrated multiomics analysis of 74 CP and BC samples using whole-genome and exome sequencing, transcriptome and methylome profiling, and chromatin immunoprecipitation followed by high-throughput sequencing. Employing pathway-based analysis, we found the BC genome was significantly enriched for mutations affecting components of the polycomb repressive complex (PRC) pathway. While transcriptomically, BC progenitors were enriched and depleted for PRC1- and PRC2-related gene sets respectively. By integrating our data sets, we determined that BC progenitors undergo PRC-driven epigenetic reprogramming toward a convergent transcriptomic state. Specifically, PRC2 directs BC DNA hypermethylation, which in turn silences key genes involved in myeloid differentiation and tumor suppressor function via so-called epigenetic switching, whereas PRC1 represses an overlapping and distinct set of genes, including novel BC tumor suppressors. On the basis of these observations, we developed an integrated model of BC that facilitated the identification of combinatorial therapies capable of reversing BC reprogramming (decitabine+PRC1 inhibitors), novel PRC-silenced tumor suppressor genes (NR4A2), and gene expression signatures predictive of disease progression and drug resistance in CP.