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.

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.

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/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).

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).

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.

Enantioselective Arylative Dearomatization of Indoles via Pd-Catalyzed Intramolecular Reductive Heck Reactions.

A highly enantioselective intramolecular arylative dearomatization of indoles via palladium-catalyzed reductive Heck reactions was developed. The new strategy led to a series of optically active indolines bearing C2-quaternary stereocenters in modest to good yields with excellent enantioselectivities (up to 99% ee).

Evaluating the coherence and time-domain profile of quantum cascade laser frequency combs.

Recently, much attention has been focused on the generation of optical frequency combs from quantum cascade lasers. We discuss how fast detectors can be used to demonstrate the mutual coherence of such combs, and present an inequality that can be used to quantitatively evaluate their performance. We discuss several technical issues related to shifted wave interference Fourier Transform spectroscopy (SWIFTS), and show how such measurements can be used to elucidate the time-domain properties of such combs, showing that they can possess signatures of both frequency-modulation and amplitude-modulation.

Palladium-catalyzed three-component cascade reaction: facial access to densely functionalized indolizines.

A palladium-catalyzed three-component cascade reaction of 2-(2-enynyl)pyridines with nucleophiles and allyl halides has been developed, enabling the synthesis of densely functionalized indolizines in moderate to good yields. The newly developed methodology offers several practical advantages, including operational simplicity, ready availability of starting materials, and mild reaction conditions.

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.

Iodine-catalyzed 1,3-dipolar cycloaddition/oxidation/aromatization cascade with hydrogen peroxide as the terminal oxidant: general route to pyrrolo[2,1-a]isoquinolines.

We report a novel molecular iodine-catalyzed 1,3-dipolar cycloaddition/oxidation/aromatization cascade process with hydrogen peroxide as the terminal oxidant for the construction of pyrrolo[2,1-a]isoquinolines. The product pyrrolo[2,1-a]isoquinolines were obtained from reactions between simple, readily available dipolarophiles and tetrahydroisoquinolines in moderate to excellent yields without the need for a metal catalyst.

Synthesis and antitumor activity of feruloyl and caffeoyl derivatives.

We developed two efficient protocols for the synthesis of feruloyl and caffeoyl derivatives from commercial vanillin and veratraldehyde. Pharmacological activities were assessed against a panel of human cancer cell lines in vitro. Most synthesized compounds demonstrated attractive cytotoxicity. Several new compounds demonstrated significant antiproliferative and cytotoxic activities against HeLa and Bewo tumor cell lines. In particular, 5-nitro caffeic adamantyl ester showed broad spectrum of tumor inhibition in 10 cell lines, and reduced tumor weight by 36.7% in vivo when administered at a dose of 40 mg kg(-1).

Highly enantioselective construction of trifluoromethylated all-carbon quaternary stereocenters via nickel-catalyzed Friedel-Crafts alkylation reaction.

A highly enantioselective Friedel-Crafts alkylation reaction of indoles with ß-CF(3)-ß-disubstituted nitroalkenes was achieved using a Ni(ClO(4))(2)-bisoxazoline complex as a catalyst, which afforded indole-bearing chiral compounds with trifluoromethylated all-carbon quaternary stereocenters in good yields with excellent enantioselectivities (up to 97% ee). The transformation of one of the products into first a trifluoromethylated tryptamine and then a trifluoromethylated tetrahydro-ß-carboline by sequential nitro reduction and Pictet-Spengler cyclization were realized with complete preservation of enantiopurity.

The synthesis of benzo[f]isoindole-1,3-dicarboxylates via an i2-induced 1,3-dipolar cycloaddition reaction.

An I2-induced 1,3-dipolar cycloaddition reaction has been developed for the synthesis of benzo[f]isoindole-1,3-dicarboxylates from quinones and N-substituted amino esters. The reaction proceeds in good to excellent yields in one step from 3 equiv of amino ester to react with the quinone structure. The utility of this transformation has been highlighted by its use for the construction of benzo[f]isoindole-1,3-dicarboxylates, which have been identified in natural products exhibiting important biological activities.

Design, synthesis, and evaluation of 3-aryl-4-pyrrolyl-maleimides as glycogen synthase kinase-3ß inhibitors.

A series of 3-aryl-4-pyrrolyl-maleimides were designed, synthesized, and evaluated for their glycogen synthase kinase-3ß (GSK-3ß) inhibitory activity. Most compounds exhibited potent activity against GSK-3ß. Among them, compounds 11a, 11c, 11h, 11i, and 11j significantly reduced Aß-induced Tau hyperphosphorylation, showing the inhibition of GSK-3ß at the cellular level. Structure-activity relationships were discussed based on the experimental data obtained.

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.