Surface-Enriched Room-Temperature Liquid Bismuth for Catalytic CO2 Reduction.

Bismuth-based electrocatalysts are effective for carbon dioxide (CO2) reduction to formate. However, at room temperature, these materials are only available in solid state, which inevitably suffers from surface deactivation, declining current densities, and Faradaic efficiencies. Here, the formation of a liquid bismuth catalyst on the liquid gallium surface at ambient conditions is shown as its exceptional performance in the electrochemical reduction of CO2 (i.e., CO2RR). By doping a trace amount of bismuth (740 ppm atomic) in gallium liquid metal, a surface enrichment of bismuth by over 400 times (30 at%) in liquid state is obtained without atomic aggregation, achieving 98% Faradic efficiency for CO2 conversion to formate over 80 h. Ab initio molecular simulations and density functional theory calculations reveal that bismuth atoms in the liquid state are the most energetically favorable sites for the CO2RR intermediates, superior to solid Bi-sites, as well as joint GaBi-sites. This study opens an avenue for fabricating high-performing liquid-state metallic catalysts that cannot be reached by elementary metals under electrocatalytic conditions.

Visible-light-induced C(sp3)-H bromination of 4-methylthiophene derivatives with HBr/H2O2.

A convenient method to synthesize ethyl 4-(bromomethyl)thiophene-3-carboxylate derivatives has been developed via a visible-light-induced radical process in good yields and with wide functional group tolerance under air conditions and at ambient temperature. The present protocol has the advantages of a high atom economy, easy purification, and environmental friendliness as it employs HBr as the bromine source and the cheap and low-toxic H2O2 as the oxidant. The synthetic utility of this method is demonstrated by a gram scale reaction and its application in the innovative synthesis of the clinical drug relugolix.

Installation of O-glycan sulfation capacities in human HEK293 cells for display of sulfated mucins.

The human genome contains at least 35 genes that encode Golgi sulfotransferases that function in the secretory pathway, where they are involved in decorating glycosaminoglycans, glycolipids, and glycoproteins with sulfate groups. Although a number of important interactions by proteins such as selectins, galectins, and sialic acid-binding immunoglobulin-like lectins are thought to mainly rely on sulfated O-glycans, our insight into the sulfotransferases that modify these glycoproteins, and in particular GalNAc-type O-glycoproteins, is limited. Moreover, sulfated mucins appear to accumulate in respiratory diseases, arthritis, and cancer. To explore further the genetic and biosynthetic regulation of sulfated O-glycans, here we expanded a cell-based glycan array in the human embryonic kidney 293 (HEK293) cell line with sulfation capacities. We stably engineered O-glycan sulfation capacities in HEK293 cells by site-directed knockin of sulfotransferase genes in combination with knockout of genes to eliminate endogenous O-glycan branching (core2 synthase gene GCNT1) and/or sialylation capacities in order to provide simplified substrates (core1 Galß1-3GalNAcα1-O-Ser/Thr) for the introduced sulfotransferases. Expression of the galactose 3-O-sulfotransferase 2 in HEK293 cells resulted in sulfation of core1 and core2 O-glycans, whereas expression of galactose 3-O-sulfotransferase 4 resulted in sulfation of core1 only. We used the engineered cell library to dissect the binding specificity of galectin-4 and confirmed binding to the 3-O-sulfo-core1 O-glycan. This is a first step toward expanding the emerging cell-based glycan arrays with the important sulfation modification for display and production of glycoconjugates with sulfated O-glycans.

Lewis Acid Catalyzed [4 + 2] Annulation of Propargylic Alcohols with 2-Vinylanilines.

An elegant Lewis acid catalyzed, protection-free, and straightforward synthetic strategy for the assembly of a series of sophisticated polycyclic quinoline skeletons employing propargylic alcohols and 2-vinylanilines as the substrates in the presence of Yb(OTf)3 (10 mol %) and AgOTf (10 mol %) in tetrahydrofuran has been described. This annulation protocol, which proceeds through a sequential Meyer-Schuster rearrangement/nucleophilic substitution/deprotonation sequence, provides a versatile, practical, and atom-economical approach for accessing quinoline derivatives in moderate-to-good yields.

New synthetic approaches toward OCF3-containing compounds.

Fluorinated organic compounds are an important class of organic molecules and play a key role in both academic and industrial communities due to the unique nature of fluorine. Among the fluorine-containing functional groups, the OCF3 group is of vital importance because of its favorable physicochemical properties, so it frequently acts as the pivotal skeletal motif in a broad spectrum of pharmaceutical molecules, agrochemicals, natural products, and materials. Over the past few decades, a wider range of strategies for the efficient, versatile, and practical synthesis of trifluoromethoxylated compounds have been the focus of a number of research initiatives. These synthesis approaches are especially fascinating in the context of the design of agrochemicals and new drugs as established pathways for installing the OCF3 moiety. In this review, the state of the art of the synthesis of OCF3-containing compounds is summarized. It can be segmented into six categories: (1) de novo formation of the OCF3 group; (2) construction of trifluoromethoxylated compounds via trifluoromethylation of the corresponding alcohol or phenol; (3) construction of trifluoromethoxylated compounds via installing the entire OCF3 group straightaway onto a complex molecule; (4) visible-light-induced trifluoromethoxylation; (5) transition metal-catalyzed trifluoromethoxylation; and (6) construction of the trifluoromethoxylated compounds via rearrangement reactions.

Fasting serum fructose is associated with metabolic dysfunction-associated fatty liver disease: A prospective study.

AIM: The association between sugar-sweetened beverages and metabolic disorders has been well studied. However, it has not been determined whether fasting serum fructose is associated with metabolic dysfunction-associated fatty liver disease (MAFLD). METHODS: Participants were enrolled from 2011 to 2012 in Shanghai. Fasting serum fructose concentration was measured with a validated liquid chromatography-tandem mass spectrometry method. RESULTS: A total of 954 participants without diabetes were included. They were followed for an average of 3.5 years. A total of 320 (33.5%) participants had MAFLD at baseline. With the increase in fasting serum fructose level by quartile, the MAFLD prevalence was increased by 27.0%, 25.0%, 37.4%, and 44.5%, respectively (p < 0.001). Each SD increase in fasting serum fructose level was associated with a 60% increased risk of MAFLD (odds ratio 1.60; 95% confidence interval [CI], 1.36-1.88; p < 0.001). Fasting serum fructose levels were more closely associated with four components of MAFLD (hepatic steatosis, prediabetes, insulin resistance, and low high-density lipoprotein). We built a diagnostic model named the fructose fat index (FFI). The area under the receiver operating characteristic curve of the FFI was 0.879 (95% CI, 0.850-0.908) in the derivation cohort and 0.827 (95% CI, 0.776-0.878) in the validation cohort. Subsequent prospective studies found that the incidence risk of MAFLD was 2.26 times higher in the high-fructose group than in the low-fructose group among female participants (95% CI, 1.46-3.49; p < 0.001). CONCLUSION: Fasting serum fructose concentration, which mostly reflects endogenous fructose, was associated with a higher risk of MAFLD. The FFI derived from fasting serum fructose could be used to predict MAFLD.

Mucin Glycans: A Target for Cancer Therapy.

Mucin glycans are an important component of the mucus barrier and a vital defence against physical and chemical damage as well as pathogens. There are 20 mucins in the human body, which can be classified into secreted mucins and transmembrane mucins according to their distributions. The major difference between them is that secreted mucins do not have transmembrane structural domains, and the expression of each mucin is organ and cell-specific. Under physiological conditions, mucin glycans are involved in the composition of the mucus barrier and thus protect the body from infection and injury. However, abnormal expression of mucin glycans can lead to the occurrence of diseases, especially cancer, through various mechanisms. Therefore, targeting mucin glycans for the diagnosis and treatment of cancer has always been a promising research direction. Here, we first summarize the main types of glycosylation (O-GalNAc glycosylation and N-glycosylation) on mucins and the mechanisms by which abnormal mucin glycans occur. Next, how abnormal mucin glycans contribute to cancer development is described. Finally, we summarize MUC1-based antibodies, vaccines, radio-pharmaceuticals, and CAR-T therapies using the best characterized MUC1 as an example. In this section, we specifically elaborate on the recent new cancer therapy CAR-M, which may bring new hope to cancer patients.

A Review of Dual-Emission Carbon Dots and Their Applications.

Carbon dots (CDs), as a rising star among fluorescent nanomaterials with excellent optical properties and fascinating dual-emission characteristics, have attracted increasing attention in sensing, bio-imaging, drug delivery, and so on. The synthesis of dual-emission CDs (DE-CDs) and the establishment of ratiometric fluorescence sensors can effectively diminish background interference and provide more accurate results than single-emission CDs. Although DE-CDs have generated increased attention in many fields, the review articles about DE-CDs are still insufficient. Therefore, we summarized the latest results and prepared this review. This review first provides an overview of the primary synthesis route and commonly used precursors in DE-CDs synthesis. Then, the photoluminescence mechanism behind the dual-emission phenomenon was discussed. Thirdly, the application of DE-CDs in metal cation detection, food safety analysis, biosensing, cell imaging, and optoelectronic devices has been extensively discussed. Finally, the main challenges and prospects for further development are presented. This review presents the latest research progress of DE-CDs synthesis and its application in ratiometric sensing; hopefully, it can help and encourage researchers to overcome existing challenges and broaden the area of DE-CDs research.

Visible-Light-Induced Oxyalkylation of 1,2,4-Triazine-3,5(2H, 4H)-diones with Ethers via Oxidative Cross-Dehydrogenative Coupling.

An efficient and convenient method to synthesize 6-oxyalkylated 1,2,4-triazine-3,5(2H, 4H)-diones has been developed via visible-light-induced cross-dehydrogenative coupling reaction between 1,2,4-triazine-3,5(2H, 4H)-diones and ethers with a wide range of functional group tolerance. The present transformation employs the cheap and low-toxic 2-tert-butylanthraquinone as a metal-free photocatalyst and air as a green oxidant at room temperature. Moreover, this reaction can also be driven by sunlight as a clean energy resource. The synthetic utility of this method is further demonstrated by gram-scale reaction and application in the preparation of key intermediates of bioactive molecules.

Primary Amination of Ar2P(O)-H with (NH4)2CO3 as an Ammonia Source under Simple and Mild Conditions and Its Extension to the Construction of Various P-N or P-O Bonds.

A facile and efficient method for the synthesis of primary phosphinamides from Ar2P(O)-H reagents with stable and readily available ammonium carbonate as an ammonia source is disclosed herein for the first time. This ethyl bromoacetate-mediated primary amination proceeds smoothly under mild and simple conditions, without any metal catalyst or oxidant. Moreover, this method is also appropriate for the reaction of Ar2P(O)-H with a variety of amines, alcohols, and phenols to construct P-N or P-O bonds, with features of handy operation, good functional group tolerance, and broad substrate scope.

Palladium-Catalyzed Intramolecular Heck Dearomative Alkenylation of Indoles with N-Tosylhydrazones.

An elegant Pd-catalyzed intramolecular Heck dearomative alkenylation of aryl iodides with functionalized N-tosylhydrazones proceeded through a sequential dearomative carbopalladation, migratory insertion, and ß-hydride elimination in the presence of Pd(CF3COO)2 (10 mol %), PPh3 (30 mol %), and Cs2CO3 (2.0 equiv) in 1,4-dioxane (2.0 mL) at 120 °C for 14 h under an argon atmosphere. This cascade cycloaddition protocol provided a reliable and versatile approach to a sequence of structurally diverse indolines in moderate to good yields with good functional group compatibility. In addition, the synthetic robustness of the methodology is highlighted by a scaled-up experiment and derivatization of products via epoxidation and reduction reactions.

Palladium-Catalyzed Asymmetric Intramolecular Dearomative Heck Annulation of Aryl Halides to Furnish Indolines.

An unprecedented Pd-catalyzed asymmetric intramolecular cascade cyclization of aryl halides with readily available arylboronic acids proceeds through a Heck-type dearomative cyclization terminated with arylation in the presence of Pd2(dba)3 (10 mol %), Cu2O (5 mol %), and Cs2CO3 (2.0 equiv) in 1,2-dichloroethane (1.0 mL) at 100 °C for 15 h in air using BINOL-based phosphoramidite as the chiral ligand. This dearomative Heck protocol, which tolerates a broad variety of functional groups, is amenable to the generation of optically active indoline derivatives bearing all-carbon quaternary stereogenic centers in one step in moderate to excellent yields, with excellent diastereoselectivities (>20:1) and enantioselectivities (up to >99% ee). It is worth mentioning that no decrease in the enantiopurity of the indoline derivatives was observed during the synthetic transformations of the products.

Visible-Light-Induced C(sp2)-C(sp3) Cross-Dehydrogenative-Coupling Reaction of N-Heterocycles with N-Alkyl-N-methylanilines under Mild Conditions.

Disclosed herein is a cross-dehydrogenative-coupling reaction of N-heterocycles including 1,2,4-triazine-3,5(2H, 4H)-diones and quinoxaline-2(1H)-ones with N-methylanilines to form C(sp2)-C(sp3) under visible-light illumination and ambient air at room temperature. In this process, easily available Ru(bpy)3Cl2·6H2O serves as the catalyst, and air acts as the green oxidant. This method features high atom economy, environmental friendliness, and convenient operation and provides an efficient and practical access to aminomethyl-substituted N-heterocycles with extensive functional group compatibility in 40-86% yields.

Synthesis of 1,6-Dihydropyridine-3-carbonitrile Derivatives via Lewis Acid-Catalyzed Annulation of Propargylic Alcohols with (E)-3-Amino-3-phenylacrylonitriles.

A novel Lewis acid-catalyzed, highly efficient, practical, and atom-economical protocol for the synthesis of functionalized 1,2-dihydropyridine-3-carbonitrile derivatives in the presence of Bi(OTf)3 (10 mol %) in tetrahydrofuran (2.0 mL) at 80 °C for 8 h in air is described, starting from readily accessed propargylic alcohols and (E)-3-amino-3-phenylacrylonitriles. This cycloaddition protocol, which is scalable and proceeds under mild conditions, is amenable to the gram-scale construction of valuable 1,2-dihydropyridine-3-carbonitriles. Furthermore, the good functional group compatibility and broad scope of this strategy were demonstrated by a broad range of propargylic alcohols and (E)-3-amino-3-phenylacrylonitriles, with yields ranging from 34 to 96%.

Photocatalytic performance and mechanism insights of a S-scheme g-C3N4/Bi2MoO6 heterostructure in phenol degradation and hydrogen evolution reactions under visible light.

Photocatalysis with potentially low cost and sustainable utilization is a typically environmentally benign method for the degradation of organic pollutants, but the rational design and fabrication of photocatalysts with high catalytic performance is still an enormous challenge. The efficient segregation of photogenerated electron-hole pairs in photocatalysts is a key and essential factor to decide photocatalytic activity. Herein, a novel Step-scheme (S-scheme) heterojunction photocatalyst, a g-C3N4/Bi2MoO6 (g-CN/BMO) composite, was successfully fabricated using g-C3N4 nanosheet-wrapped Bi2MoO6 microspheres. By adjusting the amount of g-C3N4 in BMO, a series of g-CN/BMO composites was prepared while optimizing posttreatment temperature. The resulting g-CN/BMO indicated well the photocatalytic performance for the degradation of phenol and hydrogen evolution reactions, especially, 100 g of g-CN was integrated into 100 g of the pre-calcined BMO at 200 °C to produce 100% g-CN/BMO-200, showing the highest photocatalytic performance compared to single composite BMO, BMO-200, g-CN, and g-CN/BMO-200 with other mass ratios. Combining the results from the density functional theory calculations and the results of X-ray photoelectron spectroscopy, for S-scheme heterojunction-structured g-CN/BMO-200, the internal electric field-, band edge bending- and coulomb interaction-driven efficient segregation of photogenerated electrons and holes at the interface is elucidated to explain the photocatalytic mechanism, and the resulting holes on the VB of BMO and electrons on the CB of g-CN are responsible for the improvement of the photocatalytic performance. This study revealed that for the S-scheme g-CN/BMO composite the internal electric field, band edge bending and coulomb interaction at the interface between g-CN and BMO can not only promote the effective segregation of electrons and holes, but also retain stronger redox ability. Such an investigation provides a facile and simple strategy to fabricate novel S-scheme heterojunction-structured photocatalysts for solar energy conversion.

Direct C3 Alkoxylation of Quinoxalin-2(1H)-ones with Alcohols via Cross-Dehydrogenative Coupling under Catalyst-Free Conditions.

A facile and effective alkoxylation protocol of quinoxalin-2(1H)-ones with primary or secondary alcohols via cross-dehydrogenative coupling under catalyst-free conditions has been disclosed. This method provides a powerful and convenient access to 3-alkoxylquinoxalin-2(1H)-ones in good to excellent yields by utilizing PhI(OTFA)2 as an oxidant and allows to easily obtain potential drug molecules containing 3-alkoxylquinoxalin-2(1H)-one skeletons.

Dicyanovinyl substituted push-pull chromophores: effects of central C[double bond, length as m-dash]C/phenyl spacers, crystal structures and application in hydrazine sensing.

To discern the distinctive effect of the C[double bond, length as m-dash]C bond and the phenyl bridge on the photophysical and chemical properties of D-π-A molecular systems, three new dicyanovinyl substituted push-pull chromophores 1-3 containing either a C[double bond, length as m-dash]C bond or a phenyl ring as the central π-linker were synthesized by the Suzuki-Miyaura and Knoevenagel reactions. Together with the counterpart of 1 developed by Zhang's group (TPE-z), their optical properties and single crystal structures were systematically and comparatively investigated. Notably, the simple π-extension of a C[double bond, length as m-dash]C linker to a phenyl ring between electron donor and electron acceptor moieties could greatly affect the photophysical properties of chromophores, particularly leading to significant hypsochromic shifts in both absorption and emission spectra. Meanwhile, as a node of twisted sections in chromophores, the C[double bond, length as m-dash]C bond was demonstrated to play an important role in the nonradiative relaxation of excited states, as compared to the rigid phenyl spacer. Moreover, the three chromophores were found to display spectral responses to hydrazine with slightly different sensitivities, and visual detection of hydrazine in the gaseous state was achieved via using readily fabricated paper test strips.

Ratiometric fluorescence detection of Hg2+ based on gold nanocluster/carbon quantum dots nanohybrids.

Ratiometric fluorescence sensing methods are widely used in analysis and detection due to their high sensitivity and stability. In this work, a ratiometric fluorescence method for sensitive detection of Hg2+ was established using a gold nanoclusters/carbon quantum dots (AuNCs/CQDs) nanohybrid probe. The AuNCs/CQDs nanohybrids probe were simply constructed by mixing blue-light-emitting gold nanoclusters (AuNCs) with an orange-emissive carbon quantum dots (CQDs). The probe had two fluorescence emission peaks at 434 nm and 561 nm when the excitation wavelength was 375 nm. With the addition of Hg2+, the fluorescence at 434 nm decreased and the fluorescence at 561 nm remained unchanged; the fluorescence intensity ratio Δ(F434/F561) and Hg2+ concentration have a good linear relationship in the range of 8.32 × 10-7 to 7.69 × 10-5 mol L-1, and the limit of detection (LOD) is 3.58 × 10-7 mol L-1. The method was applied in the detection of Hg2+ in cosmetics and wastewater, and has potential applications for detecting Hg2+ in other samples.

A simple and accurate ratiometric sensor for determination of dopamine based on dual-emission carbon dots.

Dopamine (DA) is a neuromodulatory molecule that plays critical roles in many biological processes. The dysfunctions of the DA system are closely associated with several nervous system diseases. Therefore, it is urgent to establish a simple and accurate method for DA analysis. In this study, an economic and accurate DA ratiometric sensor was established using dual-emission carbon dots (DE-CDs). DE-CDs were first synthesized by the one-step solvothermal method and two separate fluorescence emission peaks at 340 and 500 nm were observed under the excitation of 310 nm. In the presence of Hg2+, the fluorescence signal at 340 nm was significantly quenched, while the signal at 500 nm keeps stable. Upon adding DA, the quenched signal at 340 nm was significantly recovered, whereas the signal at 500 nm remains stable. Therefore, a novel ratiometric sensor for DA analysis was established. This method shows a good linear range from 500 nM to 100 µM, and the detection limit was calculated to be 80 nM. Moreover, this established method shows excellent specificity and could be applied in real sample analysis, showing great potential for application in clinical research.

The change of non-alcoholic fatty liver disease is associated with risk of incident diabetes.

Background & aims: The effect of change in non-alcoholic fatty liver disease (NAFLD) status on incident diabetes has not been well studied. We aimed to investigate the association of NAFLD development and remission with the risk of incident diabetes during a median of 3.5-year follow-up. Methods: A total of 2690 participants without diabetes were recruited in 2011-2012 and assessed for incident diabetes in 2014. Abdominal ultrasonography was used to determine the change of NAFLD. 75 g oral glucose tolerance test (OGTT) was performed to determine diabetes. NAFLD severity was assessed using Gholam's model. The odds ratios (ORs) for incident diabetes were estimated by logistic regression models. Results: NAFLD was developed in 580 (33.2%) participants and NAFLD remission occurred in 150 (15.9%) participants during a median of 3.5-year follow-up. A total of 484 participants developed diabetes during follow-up, including 170 (14.6%) in consistent non-NAFLD group, 111 (19.1%) in NAFLD developed group, 19 (12.7%) in NAFLD remission group, and 184 (23.2%) in sustained NAFLD group. The development of NAFLD increased the risk of incident diabetes by 43% (OR, 1.43; 95%CI, 1.10-1.86) after adjustment for multiple confounders. Compared with sustained NAFLD group, remission of NAFLD reduced the risk of incident diabetes by 52% (OR, 0.48; 95%CI, 0.29-0.80). The effect of NAFLD alteration on incident diabetes was not changed after adjustment for body mass index or waist circumference, change of body mass index or waist circumference. In NAFLD remission group, participants with non-alcoholic steatohepatitis (NASH) at baseline were more likely to develop diabetes (OR, 3.03; 95%CI, 1.01-9.12). Conclusions: NAFLD development increases the risk of incident diabetes, whereas NAFLD remission reduces the risk of incident diabetes. Moreover, presence of NASH at baseline could attenuate the protective effect of NAFLD remission on incident diabetes. Our study suggests that early intervention of NAFLD and maintenance of non-NAFLD are important for prevention of diabetes.