Recent advances in metasurface design and quantum optics applications with machine learning, physics-informed neural networks, and topology optimization methods.

As a two-dimensional planar material with low depth profile, a metasurface can generate non-classical phase distributions for the transmitted and reflected electromagnetic waves at its interface. Thus, it offers more flexibility to control the wave front. A traditional metasurface design process mainly adopts the forward prediction algorithm, such as Finite Difference Time Domain, combined with manual parameter optimization. However, such methods are time-consuming, and it is difficult to keep the practical meta-atom spectrum being consistent with the ideal one. In addition, since the periodic boundary condition is used in the meta-atom design process, while the aperiodic condition is used in the array simulation, the coupling between neighboring meta-atoms leads to inevitable inaccuracy. In this review, representative intelligent methods for metasurface design are introduced and discussed, including machine learning, physics-information neural network, and topology optimization method. We elaborate on the principle of each approach, analyze their advantages and limitations, and discuss their potential applications. We also summarize recent advances in enabled metasurfaces for quantum optics applications. In short, this paper highlights a promising direction for intelligent metasurface designs and applications for future quantum optics research and serves as an up-to-date reference for researchers in the metasurface and metamaterial fields.

Engineered bacteria producing aryl-hydrocarbon receptor agonists protect against ethanol-induced liver disease in mice.

BACKGROUND AND PURPOSE: Gut bacteria metabolize tryptophan into indoles. Intestinal levels of the tryptophan metabolite indole-3-acetic acid are reduced in patients with alcohol-associated hepatitis. Supplementation of indole-3-acetic acid protects against ethanol-induced liver disease in mice. The aim of this study was to evaluate the effect of engineered bacteria producing indoles as Aryl-hydrocarbon receptor (Ahr) agonists. METHODS: C57BL/6 mice were subjected to chronic-plus-binge ethanol feeding and orally given PBS, control Escherichia coli Nissle 1917 (EcN) or engineered EcN-Ahr. The effects of EcN and EcN-Ahr were also examined in mice lacking Ahr in interleukin 22 (Il22)-producing cells. RESULTS: Through the deletion of endogenous genes trpR and tnaA, coupled with overexpression of a feedback-resistant tryptophan biosynthesis operon, EcN-Ahr were engineered to overproduce tryptophan. Additional engineering allowed conversion of this tryptophan to indoles including indole-3-acetic acid and indole-3-lactic acid. EcN-Ahr ameliorated ethanol-induced liver disease in C57BL/6 mice. EcN-Ahr upregulated intestinal gene expression of Cyp1a1, Nrf2, Il22, Reg3b, and Reg3g, and increased Il22-expressing type 3 innate lymphoid cells. In addition, EcN-Ahr reduced translocation of bacteria to the liver. The beneficial effect of EcN-Ahr was abrogated in mice lacking Ahr expression in Il22-producing immune cells. CONCLUSIONS: Our findings indicate that tryptophan metabolites locally produced by engineered gut bacteria mitigate liver disease via Ahr-mediated activation in intestinal immune cells.

An engineered bacterial therapeutic lowers urinary oxalate in preclinical models and in silico simulations of enteric hyperoxaluria.

Enteric hyperoxaluria (EH) is a metabolic disease caused by excessive absorption of dietary oxalate leading to the formation of chronic kidney stones and kidney failure. There are no approved pharmaceutical treatments for EH. SYNB8802 is an engineered bacterial therapeutic designed to consume oxalate in the gut and lower urinary oxalate as a potential treatment for EH. Oral administration of SYNB8802 leads to significantly decreased urinary oxalate excretion in healthy mice and non-human primates, demonstrating the strain's ability to consume oxalate in vivo. A mathematical modeling framework was constructed that combines in vitro and in vivo preclinical data to predict the effects of SYNB8802 administration on urinary oxalate excretion in humans. Simulations of SYNB8802 administration predict a clinically meaningful lowering of urinary oxalate excretion in healthy volunteers and EH patients. Together, these findings suggest that SYNB8802 is a promising treatment for EH.

4.7 THz asymmetric beam multiplexer for GUSTO.

A full demonstration of the Fourier phase grating used as 4.7 THz local oscillator (LO) multiplexer for Galactic/Extragalactic ULDB Spectroscopic Terahertz Observatory (GUSTO) is presented in this paper, including its design, modeling, tolerance analysis, and experimental characterizations of the angular and intensity distributions among 2 × 4 output beams and the power efficiency. A quantum cascade laser (QCL) is used to generate the input beam for evaluation of the grating performance in its all relevant aspects with an accuracy level never reported before, where good agreements with modeling results are found. This is the first asymmetric-profile grating fully modelled and characterized at a THz frequency, that further confirms the versatility of this technology for providing an intermediate optical element for feeding multiple array detectors with a single radiation source at such a scientifically interesting frequency regime.

3.9 THz spatial filter based on a back-to-back Si-lens system.

We present a terahertz spatial filter consisting of two back-to-back (B2B) mounted elliptical silicon lenses and an opening aperture defined on a thin gold layer between the lenses. The beam filtering efficiency of the B2B lens system is investigated by simulation and experiment. Using a unidirectional antenna coupled 3rd-order distributed feedback (DFB) quantum cascade laser (QCL) at 3.86 THz as the source, the B2B lens system shows 72% transmissivity experimentally with a fundamental Gaussian mode as the input, in reasonably good agreement with the simulated value of 80%. With a proper aperture size, the B2B lens system is capable of filtering the non-Gaussian beam from the QCL to a nearly fundamental Gaussian beam, where Gaussicity increases from 74% to 99%, and achieves a transmissivity larger than 30%. Thus, this approach is proven to be an effective beam shaping technique for QCLs, making them to be suitable local oscillators in the terahertz range with a Gaussian beam. Besides, the B2B lens system is applicable to a wide frequency range if the wavelength dependent part is properly scaled.

Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity.

Synthetic biology is a powerful tool to create therapeutics which can be rationally designed to enable unique and combinatorial functionalities. Here we utilize non-pathogenic E coli Nissle as a versatile platform for the development of a living biotherapeutic for the treatment of cancer. The engineered bacterial strain, referred to as SYNB1891, targets STING-activation to phagocytic antigen-presenting cells (APCs) in the tumor and activates complementary innate immune pathways. SYNB1891 treatment results in efficacious antitumor immunity with the formation of immunological memory in murine tumor models and robust activation of human APCs. SYNB1891 is designed to meet manufacturability and regulatory requirements with built in biocontainment features which do not compromise its efficacy. This work provides a roadmap for the development of future therapeutics and demonstrates the transformative potential of synthetic biology for the treatment of human disease when drug development criteria are incorporated into the design process for a living medicine.

81 supra-THz beams generated by a Fourier grating and a quantum cascade laser.

Large heterodyne receiver arrays (~100 pixel) allow astronomical instrumentations to map more area within limited space mission lifetime. One challenge is to generate multiple local oscillator (LO) beams. Here, we succeeded in generating 81 beams at 3.86 THz by combining a reflective, metallic Fourier grating with an unidirectional antenna coupled 3rd-order distributed feedback (DFB) quantum cascade laser (QCL). We have measured the diffracted 81 beams by scanning a single pyroelectric detector at a plane, which is in the far field for the diffraction beams. The measured output beam pattern agrees well with a simulated result from COMSOL Multiphysics, with respect to the angular distribution and power distribution among the 81 beams. We also derived the diffraction efficiency to be 94 ± 3%, which is very close to what was simulated for a manufactured Fourier grating (97%). For an array of equal superconducting hot electron bolometer mixers, 64 out of 81 beams can pump the HEB mixers with similar power, resulting in receiver sensitivities within 10%. Such a combination of a Fourier grating and a QCL can create an LO with 100 beams or more, enabling a new generation of large heterodyne arrays for astronomical instrumentation.

Palladium-catalyzed allylation of aminophenol with alkynes to construct C-N bonds.

A method for the allylic alkylation of aminophenol with alkynes was developed using a palladium-catalysed allylation reaction with 100% atom economy. A series of structurally diverse N-allylic substituted allylamines were synthesized in good yields with high chemo-, regio-, and stereoselectivities under mild conditions.

Enantioselective alkynylation of N-sulfonyl α-ketiminoesters via a Friedel-Crafts alkylation strategy.

Enantioselective alkynylation of cyclic N-sulfonyl α-ketiminoesters with terminal alkynes was developed by using an Ni(ClO4)2/(R)-DTBM-Segphos complex as a catalyst. A range of propargylic amides bearing quaternary stereocenters were afforded in excellent enantioselectivities (up to 97% ee). Theoretical studies revealed that this reaction proceeded via a Friedel-Crafts-type reaction pathway.

Enantioselective [2 + 2] cycloaddition of N-allenamides with cyclic N-sulfonylketimines: access to polysubstituted azetidines bearing quaternary stereocenters.

A Ni(ClO4)2-catalyzed enantioselective [2 + 2] cycloaddition of N-allenamides with cyclic N-sulfonylketimines was developed, which regioselectively occurred at the proximal C[double bond, length as m-dash]C bonds of the N-allenamides. Broad substrate scope of N-allenamides and cyclic N-sulfonylketimines was observed. A range of fused polysubstituted azetidines bearing quaternary stereocenters were afforded in good yields and with excellent enantioselectivities (up to 99%).

Spirooxindole synthesis via palladium-catalyzed dearomative reductive-Heck reaction.

Palladium-catalyzed intramolecular dearomative reductive-Heck reaction of C2-substituted indoles is developed, which provides access to structurally diverse 3,2'-spiropyrrolidine oxindoles. By changing the hydride source to AcONa base, direct C3-arylation products [2,3-b]quinolinones are achieved in good yields. The reaction of C2-substituted benzofuran is also realized, delivering the desired spiro-product.

Palladium-catalyzed dearomative arylalkynylation of indoles.

A palladium-catalyzed indole dearomative bisfunctionalization via a domino arylation/alkynylation sequence has been developed, which provides a reliable approach to a series of structurally diverse tetracyclic indolines bearing vicinal tertiary and quaternary stereocenters in moderate to good yields and excellent diastereoselectivities.

Cu(I)-Catalyzed Enantioselective Friedel-Crafts Alkylation of Indoles with 2-Aryl-N-sulfonylaziridines as Alkylating Agents.

A highly enantioselective Friedel-Crafts alkylation of indoles with N-sulfonylaziridines as alkylating agents has been developed by utilizing the complex of Cu(CH3CN)4BF4/(S)-Segphos as a catalyst. A range of optically active tryptamine derivatives are obtained in good to excellent yields and enantioselectivities (up to >99% ee) via a kinetic resolution process.

Optical performance of an ultra-sensitive horn-coupled transition-edge-sensor bolometer with hemispherical backshort in the far infrared.

The next generation of far infrared space observatories will require extremely sensitive detectors that can be realized only by combining extremely low intrinsic noise with high optical efficiency. We have measured the broad-band optical response of ultra-sensitive transtion edge sensor (TES) bolometers (NEP≈2aW/Hz) in the 30-60-µm band where radiation is coupled to the detectors with a few-moded conical feedhorn and a hemispherical backshort. We show that these detectors have an optical efficiency of 60% (the ratio of the power detected by the TES bolometer to the total power propagating through the feedhorn). We find that the measured optical efficiency can be understood in terms of the modes propagating through the feedhorn with the aid of a spatial mode-filtering technique.

Palladium/l-Proline-Catalyzed Enantioselective α-Arylative Desymmetrization of Cyclohexanones.

A highly enantioselective palladium/l-proline-catalyzed α-arylative desymmetrization of cyclohexanones was developed. The new strategy for α-arylation reaction led to a series of optically active morphan derivatives bearing α-carbonyl tertiary stereocenters in good yields with excellent enantioselectivities (up to 99% ee).

A novel GSK-3ß inhibitor YQ138 prevents neuronal injury induced by glutamate and brain ischemia through activation of the Nrf2 signaling pathway.

AIM: To discover neuroprotective compounds and to characterize the discovered active compound YQ138 as a novel GSK-3ß inhibitor. METHODS: Primary rat cerebellar granule cells (CGCs) were treated with glutamate, and cell viability was analyzed with MTT assay, which was used as in vitro model for screening neuroprotective compounds. Active compound was further tested in OGD- or serum deprivation-induced neuronal injury models. The expression levels of GSK-3ß downstream proteins (Nrf2, HO-1, NQO1, Tau and ß-catenin) were detected with Western blotting. For evaluating the neuroprotective effects in vivo, adult male rats were subjected to transient middle cerebral artery occlusion (tMCAO), then treated with YQ138 (10 mg/kg, iv) at 2, 4 and 6 h after ischemia onset. RESULTS: From a compound library consisting of about 2000 potential kinase inhibitors, YQ138 was found to exert neuroprotective effects: pretreatment with YQ138 (0.1-40 µmol/L) dose-dependently inhibited glutamate-induced neuronal death. Furthermore, pretreatment with YQ138 (10 µmol/L) significantly inhibited OGD- or serum deprivation-induced neuronal death. Among a panel of seven kinases tested, YQ138 selectively inhibited the activity of GSK-3ß (IC50=0.52 nmol/L). Furthermore, YQ138 dose-dependently increased the expression of ß-catenin, and decreased the phosphorylation of Tau in CGCs. Moreover, YQ138 significantly increased the expression of GSK-3ß downstream antioxidative proteins Nrf2, HO-1, NQO1, GSH and SOD in CGCs. In rats with tMCAO, administration of YQ138 significantly decreased infarct volume, improved the neurological deficit, and increased the expression of Nrf2 and HO-1 and the activities of SOD and GSH in the cerebral cortex. CONCLUSION: A novel GSK-3ß inhibitor YQ138 effectively suppresses brain ischemic injury in vitro and in vivo.

Lewis Acid Catalyzed Friedel-Crafts Alkylation of Alkenes with Trifluoropyruvates.

A Friedel-Crafts alkylation reaction of styrenes with trifluoropyruvates has been developed, which delivered allylic alcohols in excellent yields (up to 98%) using the Ni(ClO4)2·6H2O/bipyridine complex as a catalyst. The asymmetric reaction was catalyzed by the chiral Cu(OTf)2/bisoxazoline complex to afford the corresponding chiral allylic alcohols bearing trifluoromethylated quaternary stereogenic centers in moderate enantioselectivities (up to 75% ee).

Enantioselective Friedel-Crafts Alkylation Reactions of 3-Substituted Indoles with Electron-Deficient Alkenes.

Highly enantioselective Friedel-Crafts C2-alkylation reactions of 3-substituted indoles with α,ß-unsaturated esters and nitroalkenes were developed using chiral Lewis acids as catalysts, which afforded chiral indole derivatives bearing C2-benzylic stereogenic centers in good to excellent yields (up to 99%) and enantioselectivities (up to 96% ee).

Dual catalysis for the redox annulation of nitroalkynes with indoles: enantioselective construction of indolin-3-ones bearing quaternary stereocenters.

The enantioselective redox annulation of nitroalkynes with indoles is enabled by gold/chiral phosphoric acid dual catalysis. A range of indolin-3-one derivatives bearing quaternary stereocenters at the C2 position were afforded in good yields and excellent enantioselectivities (up to 96 % ee) from readily available starting materials.