Nitazoxanide protects against experimental ulcerative colitis through improving intestinal barrier and inhibiting inflammation.

Ulcerative colitis is a chronic disease with colonic mucosa injury. Nitazoxanide is an antiprotozoal drug in clinic. Nitazoxanide and its metabolite tizoxanide have been demonstrated to activate AMPK and inhibit inflammation, therefore, the aim of the present study is to investigate the effect of nitazoxanide on dextran sulfate sodium (DSS)-induced colitis and the underlying mechanism. Oral administration of nitazoxanide ameliorated the symptoms of mice with DSS-induced colitis, as evidenced by improving the increased disease activity index (DAI), the decreased body weight, and the shortened colon length. Oral administration of nitazoxanide ameliorated DSS-induced intestinal barrier dysfunction and reduced IL-6 and IL-17 expression in colon tissues. Mechanistically, nitazoxanide and its metabolite tizoxanide treatment activated AMPK and inhibited JAK2/STAT3 signals. Nitazoxanide and tizoxanide treatment increased caudal type homeobox 2 (CDX2) expression, increased alkaline phosphatase (ALP) activity and promoted tight junctions in Caco-2 cells. Nitazoxanide and tizoxanide treatment restored the decreased zonula occludens-1(ZO-1) and occludin protein levels induced by LPS or IL-6 in Caco-2 cells. On the other hand, nitazoxanide and tizoxanide regulated macrophage bias toward M2 polarization, as evidenced by the increased arginase-1expression in bone marrow-derived macrophages (BMDM). Nitazoxanide and tizoxanide reduced the increased IL-6, iNOS and CCL2 pro-inflammatory gene expressions and inhibited JAK2/STAT3 activation in BMDM induced by LPS. In conclusion, nitazoxanide protects against DSS-induced ulcerative colitis in mice through improving intestinal barrier and inhibiting inflammation and the underlying mechanism involves AMPK activation and JAK2/STAT3 inhibition.

Electron-Poor Acridones and Acridiniums as Super Photooxidants in Molecular Photoelectrochemistry by Unusual Mechanisms.

Electron-deficient acridones and in situ generated acridinium salts are reported as potent, closed-shell photooxidants that undergo surprising mechanisms. When bridging acyclic triarylamine catalysts with a carbonyl group (acridones), this completely diverts their behavior away from open-shell, radical cationic, 'beyond diffusion' photocatalysis to closed-shell, neutral, diffusion-controlled photocatalysis. Brønsted acid activation of acridones dramatically increases excited state oxidation power (by +0.8 V). Upon reduction of protonated acridones, they transform to electron-deficient acridinium salts as even more potent photooxidants (*E1/2 =+2.56-3.05 V vs SCE). These oxidize even electron-deficient arenes where conventional acridinium salt photooxidants have thusfar been limited to electron-rich arenes. Surprisingly, upon photoexcitation these electron-deficient acridinium salts appear to undergo two electron reductive quenching to form acridinide anions, spectroscopically-detected as their protonated forms. This new behaviour is partly enabled by a catalyst preassembly with the arene, and contrasts to conventional SET reductive quenching of acridinium salts. Critically, this study illustrates how redox active chromophoric molecules initially considered photocatalysts can transform during the reaction to catalytically active species with completely different redox and spectroscopic properties.

Transient absorption spectroscopy based on uncompressed hollow core fiber white light proves pre-association between a radical ion photocatalyst and substrate.

We present a hollow-core fiber (HCF) based transient absorption experiment, with capabilities beyond common titanium:sapphire based setups. By spectral filtering of the HCF spectrum, we provide pump pulses centered at 425 nm with several hundred nJ of pulse energy at the sample position. By employing the red edge of the HCF output for seeding CaF2, we obtain smooth probing spectra in the range between 320 and 900 nm. We demonstrate the capabilities of our experiment by following the ultrafast relaxation dynamics of a radical cationic photocatalyst to prove its pre-association with an arene substrate, a phenomenon that was not detectable previously by steady-state spectroscopic techniques. The detected preassembly rationalizes the successful participation of radical ionic photocatalysts in single electron transfer reactions, a notion that has been subject to controversy in recent years.

Protocol to estimate cell type proportions from bulk RNA-seq using DAISM-DNNXMBD.

Computational protocols for cell type deconvolution from bulk RNA-seq data have been used to understand cellular heterogeneity in disease-related samples, but their performance can be impacted by batch effect among datasets. Here, we present a DAISM-DNN protocol to achieve robust cell type proportion estimation on the target dataset. We describe the preparation of calibrated samples from human blood samples. We then detail steps to train a dataset-specific deep neural network (DNN) model and cell type proportion estimation using the trained model. For complete details on the use and execution of this protocol, please refer to Lin et al. (2022).

Synthetic Molecular Photoelectrochemistry: New Frontiers in Synthetic Applications, Mechanistic Insights and Scalability.

Synthetic photoelectrochemistry (PEC) is receiving increasing attention as a new frontier for the generation and handling of reactive intermediates. PEC permits selective single-electron transfer (SET) reactions in a much greener way and broadens the redox window of possible transformations. Herein, the most recent contributions are reviewed, demonstrating exciting new opportunities, namely, the combination of PEC with other reactivity paradigms (hydrogen-atom transfer, radical polar crossover, energy transfer sensitization), scalability up to multigram scale, novel selectivities in SET super-oxidations/reductions and the importance of precomplexation to temporally enable excited radical ion catalysis.

Removal of 4-chlorophenol from polluted water by aluminum-iron alloys.

Chlorophenols are extremely toxic to the environment and recalcitrant to biological degradation. Herein chemical degradation of 4-chlorophenol (4-CP) from aqueous solutions by zero-valent aluminum (Al), zero-valent iron (Fe), Al and Fe mixtures (Al/Fe mass ratio 90/10, labeled as Al/Fe10) and Al-Fe alloy (Al/Fe mass ratio 90/10, labeled as Al-Fe10) were investigated. No removal was found for 50 mg·L-1 4-CP under anoxic conditions at initial pH 2.5 during a period of 10 hrs while 56%, 83%, 78% and 99% of 4-CP were removed by Fe, Al, Al/Fe10 and Al-Fe10, respectively under aeration conditions. The removal of 4-CP by Al/Fe10 mixtures was primarily in the Fe mode in the beginning 4 h and then transitioned to the Al mode. The removal of 4-CP by Al-Fe10 alloy was accomplished via two intermediate products, hydroquinone (HQ) and 4-chlorocatechol (4-CC), and it was speculated that reactive oxygen species and hydroxyl radicals (·OH) play an important role in the degradation of 4-CP and that Al-Fe intermetallic compounds might catalyze the reactions. This study demonstrates that alloying Al with Fe offers a promising strategy for developing new materials for water and wastewater remediation.

Stereocontrolled synthesis of resolvin D1.

We studied the synthesis of RvD1, a pro-resolving mediator. The intermediate containing vic-diol and enal functional groups was prepared via the oxidation of the γ,δ-epoxy alcohol followed by the epoxide ring opening in one pot. The C11-aldehyde in the resulting enal was converted to the trans iodo-olefin by reaction with TMSC(N2)Li and subsequent hydrozirconation using in situ generated Cp2Zr(H)Cl followed by iodination. The trans enynyl alcohol was synthesized by the reaction of the TMS-containing epoxy alcohol with lithium TMS-acetylide. Finally, two fragments were joined by the Sonogashira coupling, and the triple bond was reduced to afford RvD1 stereoselectively.

Rhodium(III)-Catalyzed C-H Functionalization in Water for Isoindolin-1-one Synthesis.

Rhodium-catalyzed green synthesis of isoindolin-1-ones via a sequential C-H activation/allene formation/cyclization pathway by applying water as solvent is reported. The reaction is highly regioselective, tolerating some potentially useful functional groups.

Palladium-catalysed formation of vicinal all-carbon quaternary centres via propargylation.

Construction of two vicinal all-carbon quaternary carbon centres is of great importance due to the common presence of such units in natural and unnatural molecules with attractive functions. However, it remains a significant challenge. Here, we have developed a palladium-catalysed general coupling for the efficient connection of two tertiary carbon atoms: Specifically, propargylic carbonate has been treated with a fully loaded soft functionalized nucleophile to connect such two fully loaded carbon atoms with a simple palladium catalyst. It is observed that the central chirality in the optically active tertiary propargylic carbonates has been remembered and transferred into the products with very high efficiency. The triple bond and the functional groups such as ester, cyano and unsaturated C-C bonds make this method a relatively general solution for such a purpose due to their high synthetic versatility.

TfOH-catalyzed domino cycloisomerization/hydrolytic defluorination of 2,3-allenyl perfluoroalkyl ketones.

A unique TfOH-catalyzed domino cycloisomerization/hydrolytic defluorination reaction of easily available n-perfluoroalkyl allenones in the presence of H2O providing furanyl perfluoroalkyl ketones has been developed. The (18)O-labelling experiments confirmed that the oxygen atom of the carbonyl group in the final products originates from water.

A C-H bond activation-based catalytic approach to tetrasubstituted chiral allenes.

Enantioselective synthesis of fully substituted allenes has been a challenge due to the non-rigid nature of the axial chirality, which spreads over three carbon atoms. Here we show the commercially available simple Rh complex may catalyse the CMD (concerted metalation/deprotonation)-based reaction of the readily available arenes with sterically congested tertiary propargylic carbonates at ambient temperature affording fully substituted allenes. It is confirmed that the excellent designed regioselectivity for the C-C triple bond insertion is induced by the coordination of the carbonyl group in the directing carbonate group as well as the steric effect of the tertiary O-linked carbon atom. When an optically active carbonate was used, surprisingly high efficiency of chirality transfer was realized, affording fully substituted allenes in excellent enantiomeric excess (ee).

Rhodium-catalyzed C-H functionalization-based approach to eight-membered lactams.

A Rh(iii) catalyzed formal [4 + 2 + 2] cyclization of N-pivaloyloxybenzamides 1 with 1,6-allene-enes 2 by C-H functionalization is reported. The reactions occur at room temperature and are compatible with air and moisture with a tolerance of many synthetically useful functional groups. The follow-up modifications of the products have been demonstrated. After careful mechanistic studies and DFT calculation, a reaction mechanism was proposed.

Room-temperature synthesis of trisubstituted allenylsilanes via regioselective C-H functionalization.

A Rh(III)-catalyzed o-C-H bond functionalization-based allenylation reaction of allenylsilanes 2 with N-methoxybenzamides 1 affords poly-substituted allenylsilanes with a wide range of attractive functional groups in moderate to excellent yields under very mild conditions (20 °C, compatible with ambient air and moisture). Those products may be transformed to different products with attractive structural features. Careful mechanistic studies suggest the reaction proceeds via o-rhodation, regioselective insertion, and ß-H elimination.

A straightforward synthesis of cyclobutenones via a tandem Michael addition/cyclization reaction of 2,3-allenoates with organozincs.

An efficient method for synthesis of polysubstituted cyclobutenones, which are not readily available from traditional methods due to the intrinsic ring strain, is described. The reaction of 2,3-allenoates and organozinc reagents proceeds via a tandem Michael addition/cyclic 1,2-addition/elimination mechanism with the functional groups from the organozinc reagents being introduced to the 3-position of the cyclobutenone products regiospecifically in moderate to excellent yields. Application to the synthesis of stereodefined ß,γ-unsaturated enones is demonstrated.