Catalysts-Controlled Roles Exchange between 2,3-Diaryl-2H-azirines and Acetone: Chemodivergent Synthesis of Pyrroles and 3-Oxazolines.

We report two practical and step-economical methodologies for the chemodivergent synthesis of tri-substituted pyrroles and 3-oxazolines from the domino reactions of 2H-azirines and acetone. For instance, acetone served as a nucleophile to react with 2H-azirines under the basic conditions to furnish pyrroles. Upon changing the catalyst to TfOH, acetone served as an electrophile to synthesize 3-oxazolines. Moreover, the products could be synthesized on a gram scale, and the possible catalytic cycles were proposed.

Nanozyme-induced deep learning-assisted smartphone integrated colorimetric and fluorometric dual-mode for detection of tetracycline analogs.

In this work, a colorimetric and fluorescent dual-mode probe controlled by NH2-MIL-88 B (Fe, Ni) nanozymes was developed to visually detect tetracycline antibiotics (TCs) residues quantitatively, as well as accurately distinguish the four most widely used tetracycline analogs (tetracycline (TC), chrycline (CTC), oxytetracycline (OTC), and doxycycline (DC)). Colorless substrate 3,3',5,5'-tetramethylbenzidine (TMB) may be oxidized to blue oxidized TMB by the Fe Fenton reaction, which was catalyzed by the NH2-MIL-88 B (Fe, Ni) nanozyme with POD-like activity. The colorimetric detection system allows TCs to interact with NH2-MIL-88 B (Fe, Ni). This inhibits the production of ·OH, weakens the oxidation process of TMB, and ultimately lightens the blue color in the system by blocking the electron transfer between NH2-MIL-88 B (Fe, Ni) and H2O2. Furthermore, TCs can interact with NH2-MIL-88 B (Fe, Ni) as a result of the internal filtering effect, which causes the fluorescence intensity to decrease as TCs concentration increases. Additionally, a portable instrument that combines a smartphone sensing platform with colorimetric and fluorescent signals was created for the quick, visual quantitative detection of TCs. The colorimetric and fluorescent dual-mode nano platform enables color change, with detection limits (LODs) of 0.182 µM and 0.0668 µM for the spectrometer and smartphone sensor, respectively, based on the inhibition of fluorescence and enzyme-like activities by TCs. Overall, the colorimetric and fluorescence dual-mode sensor has good stability, high specificity, and an efficient way to eliminate false-positive issues associated with a single detection mode.

Integrated Transcriptomic and Proteomic Analysis Identifies Novel Regulatory Genes Associated with Plant Growth Regulator-Induced Astringency in Grape Berries.

Astringency influences the sensory characteristics and flavor quality of table grapes. We tested the astringency sensory attributes of berries and investigated the concentration of flavan-3-ols/proanthocyanidins (PAs) in skins after the application of the plant growth regulators CPPU and GA3 to the flowers and young berries of the "Summer Black" grape. Our results showed that CPPU and GA3 applications increase sensory astringency perception scores and flavan-3-ol/proanthocyanidin concentrations. Using integrated transcriptomic and proteomic analysis, differentially expressed transcripts and proteins associated with growth regulator treatment were identified, including those for flavonoid biosynthesis that contribute to the changes in sensory astringency levels. Transient overexpression of candidate astringency-related regulatory genes in grape leaves revealed that VvWRKY71, in combination with VvMYBPA1 and VvMYC1, could promote the biosynthesis of proanthocyanidins, while overexpression of VvNAC83 reduced the accumulation of proanthocyanidins. However, in transient promoter studies in Nicotiana benthamiana, VvWRKY71 repressed the promoter of VvMYBPA2, while VvNAC83 had no significant effect on the promoter activity of four PA-related genes, and VvMYBPA1 was shown to activate its own promoter. This study provides new insights into the molecular mechanisms of sensory astringency formation induced by plant growth regulators in grape berries.

Comparative study on chemical composition, functional properties of dietary fibers prepared from four China cereal brans.

Comparison of chemical composition and functional properties of insoluble and soluble dietary fiber (IDF, SDF) obtained from four China cereal brans was investigated. With findings, IDFs and SDFs for rice bran (RB), wheat bran (WB), highland barely bran (HBB) and tartary buckwheat bran (TBB) contained several monosaccharides such as arabinose, galactose, glucose, xylose, and galacturonic acid. The RBIDF was shrinking and formed a rugged microscopic structure, while the structure of WBIDF was dense and flat. HBBIDF and TBBIDF showed fold and flake structure. The glucose adsorption capacity of the HBBIDF was highest among all samples, which was 3.2 mmol/g. TBBIDF exhibited the highest value of cholesterol adsorption capacity (10.5 mg/g) at pH 7.0 and maximum binding capacity (BCmax, 365.2 µmol/g) for cadmium at pH 7.0 among all samples, respectively. As a result, HBBIDF and TBBIDF are potential fiber-rich ingredients in functional foods.

Properties of pyrodextrinization corn starch and their inhibitory effect on the retrogradation of fresh rice noodles.

This study was aimed to investigate the properties of pyrodextrins under different preparation conditions and the effects of pyrodextrins on the retrogradation of fresh rice noodles. Pyrodextrins were made by heating corn starch with and without lactic acid at 180 °C ranging from 1 to 6 h. The molecular weights of pyrodextrins gradually decreased, whereas the branching degree increased and the chain length shrank with the prolongation of heating time. The changes of acid-heat-treated pyrodextrins were more pronounced than those of dry-heat-treated pyrodextrins under the same treatment time. The acid-heat-treated pyrodextrins displayed higher water solubility and lower viscosity, suggesting that they could no longer gel. These results suggest that starch retrogradation could be limited by pyrodextrins, especially acid-heat-treated pyrodextrins. Then, the pyrodextrins were added to fresh rice noodles and the eating and cooking qualities were examined during storage. After 35 days of storage, the pyrodextrin with acid heating at 180 °C for 4 h showed the most effective inhibition on starch retrogradation and was suitable for fresh rice noodles as an anti-retrogradation agent. The study might supply new perspectives on restraining starch retrogradation and promoting the fresh rice noodle industry.

Compound heterozygous mutations in the helicase RTEL1 causing Hoyeraal-Hreidarsson syndrome with Blake`s pouch cyst: a case report.

BACKGROUND: Telomeres inhibit DNA damage response at the ends of the chromosome to suppress cell cycle arrest as well as ensure genome stability. Dyskeratosis congenita (DC), a telomere-related disease, includes the classical triad involving oral leukoplakia, dysplastic nails, and lacy reticular pigment in the neck and/or upper chest. Hoyeraal-Hreidarrson syndrome (HHS), a severe manifestation of DC, frequently occurs during childhood, and patients with HHS often show short-term survival and thus do not exhibit all mucocutaneous manifestations or syndromic features. CASE: We report here a patient with HHS characterized by the proband`s clinical attributes, such as growth delay, bone marrow failure, microcephaly, defects in body development, and the absence of cerebellar hypoplasia combined with Blake`s pouch cyst. By using exome sequencing, novel compound heterozygous mutations (c.1451C > T and c.1266+3del78bp) were detected in the RTEL1 (regulator of telomere elongation helicase 1) gene. CONCLUSIONS: The DNA helicase RTEL1 plays a role in genome stability, DNA replication, telomere maintenance, and genome repair. Terminal restriction fragment length analysis revealed a significantly shorter telomere length of the proband. Our findings provided evidence that compound heterozygous RTEL1 mutations cause HHS.

The Enediolate Chemistry of Free Carboxylic Acids.

The synthetic methodologies for the α-functionalization of free carboxylic acids through the enediolate intermediates are summarized in this review. In general, the enediolates could be generated in situ or transiently from free carboxylic acids with a stoichiometric or catalytic amount of protection reagents, including metal, boron, and silicon reagents. The in situ or transient generated enediolates were subsequently subjected to racemic or asymmetric reactions with various electrophiles, producing the α-functionalized free carboxylic acids in a single step. In addition, the enediolate could undergo an α-oxidation reaction with TEMPO through the radical process.

Arylboronic Acid Catalyzed Dehydrative Mono-/Dialkylation Reactions of ß-Ketoacids and Alcohols.

The dehydrative mono-/dialkylation reactions of alcohols and ß-ketoacids were realized under arylboronic acid catalysis, furnishing a series of ß-aryl ketones and ß-ketoesters in yields of 15-99%, with CO2 and H2O being the byproducts. In this context, the decarboxylative alkylation reaction occurred to give ß-aryl ketones at 50 °C, while the decarboxylation was suppressed to generate dialkylated ester products at 0 °C. A possible catalytic cycle was proposed based on control experiments.

Chiral ScIII-N,N'-Dioxide-Catalyzed 1,3-Dipolar Cycloaddition of Diaziridines with Chalcones.

A highly enantioselective 1,3-dipolar cycloaddition of meso-diaziridines with chalcones was realized by utilizing the ScIII-N,N'-dioxide complex as the catalyst. In this transformation, the 1,3-dipole intermediates generated from the C-N bond cleavage of diaziridine were trapped by chiral N,N'-dioxide/scandium(III) complex activated chalcones to undergo enantioselective 1,3-dipolar cycloaddition. A range of chiral 1,5-diazabicylo[3.3.0]octane derivatives were readily synthesized in good yields with high diastereo- and enantioselectivities.

Enantioselective Vinylogous Michael-Aldol Reaction To Synthesize Spirocyclohexene Pyrazolones in Aqueous Media.

An efficient asymmetric vinylogous Michael-aldol domino reaction between α-arylidene pyrazolinones and ß,γ-unsaturated-α-ketoesters catalyzed by a chiral N, N'-dioxide-ScIII complex in aqueous media has been established. A variety of spirocyclohexene pyrazolones with three stereocenters including vicinal tetrasubstituted stereocenters were obtained in excellent yields with good diastereoselectivities and enantioselectivities. A retro-aldol process was observed, which led to epimerization at the spirocyclic quaternary carbon center.

Effect of iron loading on the performance and structure of Fe/ZSM-5 catalyst for the selective catalytic reduction of NO with NH3.

A series of Fe/ZSM-5 catalysts with different Fe contents were prepared by impregnation method. The catalysts were characterized by TEM, XRD, H2 temperature-programed reduction (H2-TPR), temperature-programed desorption of ammonia (NH3-TPD), and in situ diffuse-reflectance infrared Fourier transform spectroscopy (DRIFTS), and the catalytic activity test was also carried out on selective catalytic reduction (SCR) denitration device. Results showed that the single metal iron-supported ZSM-5 catalyst has high deNOx activity in the medium-high temperature range, and the optimal loading of Fe active component is 10 wt%; the deNOx efficiency over 80% at the range of 350-450 °C and 431 °C reaches the maximum of 96.91%. Iron species can be finely dispersed on the surface of the carrier as amorphous oxides, and the crystalline structure of zeolite is retained. The significant redox performance, highly dispersed nanoparticles, and rich Lewis acid sites on the surface of catalyst are favorable for the SCR denitration reaction. Fe/ZSM-5 10 wt% catalyst has rich Lewis acid sites and less B acid sites and Lewis acidic sites play an important role during the reaction. Only Eley-Rideal (E-R) mechanism existed during the NH3-SCR reaction process, and there is no denitration reaction being accomplished by L-H mechanism at 150 °C.

Copper-Catalyzed Asymmetric Addition of Tertiary Carbon Nucleophiles to 2 H-Azirines: Access to Chiral Aziridines with Vicinal Tetrasubstituted Stereocenters.

A catalytic asymmetric nucleophilic addition of tertiary carbon nucleophiles to 2 H-azirines was established in the presence of the chiral N,N'-dioxide/CuII complex. Various chiral aziridines with vicinal tetrasubstituted stereocenters were obtained in high yields with excellent diastereoselectivities and enantioselectivities. Moreover, on the basis of the control experiments, X-ray structures of the products, and catalyst, a possible transition state was proposed to explain the stereoselectivity.

Uptake and transport of pullulan acetate nanoparticles in the BeWo b30 placental barrier cell model.

INTRODUCTION: Nanomedicine has shown a great potential in perinatal medicine because of its characteristics of sustained, controlled release and targeting ability; on the other hand, it may also lead to unexpected toxicities such as embryotoxicity and even malformation after crossing the placental barrier, but data concerning transplacental transport are scarce. Pullulan acetate (PA) nanoparticles (NPs) are a promising nanocarrier derived from natural polysaccharide; however, their transplacental transport ability and mechanism are unknown. MATERIALS AND METHODS: In this study, fluorescein isothiocyanate (FITC) conjugated PA (PA-FITC) was synthesized. PA-FITC NPs were characterized by dynamic light scattering, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The cytotoxicity of PA-FITC NPs at concentrations of 15, 30, 60, 125, 250, 500, 1,000 and 2,000 µg/mL was studied by cell counting kit-8. The human chorionic gonadotrophin (HCG) cytokine assay was conducted to evaluate the biological function of BeWo b30 cells. Endocytic mechanisms of PA-FITC NPs were investigated via fluorescence analysis. The monolayer properties were characterized by TEM, tight junction staining, transepithelial electrical resistance and fluorescein sodium transportation. The transport ability was measured in the cell based transwell model by confocal imaging and SEM. RESULTS: PA-FITC NPs were almost spherical shape with a size range of 200-300 nm. Cell viability of BeWo b30 cells was up to 100% in all groups. The concentrations of HCG increased with increasing numbers of cells and culture time, which showed the good biological function of BeWo b30 cells. PA-FITC NPs were rapidly endocytosed through caveolae-mediated endocytosis and pinocytosis, with uptake inhibition rates with nystatin (NY) and colchicines (Col) of 55% and 51% respectively. BeWo b30 cell monolayer was formed over 5 days. PA-FITC NPs were found in the cytoplasm of cells on the transwell membranes; while some NPs were found in the basolateral (fetal) compartment over 24 h. CONCLUSION: In summary, PA-FITC NPs are nontoxic, can cross the blood-placental barrier, and show mainly internalization to BeWo b30 cells through caveolae-mediated endocytosis and pinocytosis pathways, major via the former pathway. The results could benefit the adjustment and control of the transplacental transport of nanomedicines.

Dynamic kinetic asymmetric transformations of ß-halo-α-keto esters by N,N'-dioxide/Ni(ii)-catalyzed carbonyl-ene reaction.

Dynamic kinetic asymmetric transformations of racemic ß-halo-α-keto esters through carbonyl-ene reaction were realized using a chiral N,N'-dioxide-nickel(ii) complex, giving the corresponding ß-halo-α-hydroxy esters containing two vicinal chiral tri- and tetrasubstituted carbon centers in good yields and dr with excellent ee values without the use of extra bases. Meanwhile, a proposed reaction mechanism was presented according to the configuration of the product.

Catalytic Asymmetric [8+3] Annulation Reactions of Tropones or Azaheptafulvenes with meso-Aziridines.

Highly enantioselective [8+3] high-order cycloaddition reactions of tropones or azaheptafulvenes with meso-aziridines were achieved by a desymmetrization/annulation process in the presence of chiral N,N'-dioxide/Mg(OTf)2 complex. The corresponding tetrahydrocyclohepta[b][1,4]oxazines and tetrahydro-1H-cyclohepta- [b]-pyrazines were obtained in good yields (66-98 %) with excellent diastereo- and enantioselectivities (>19:1 d.r., 90-96 % ee). A possible transition state model was proposed to elucidate the origin of chiral induction based on the control experiments and X-ray crystal structure of the catalyst.

Catalytic Asymmetric Direct Vinylogous Aldol Reaction of Isatins with ß,γ-Unsaturated Butenolides.

A direct asymmetric vinylogous aldol reaction of nonactivated natural α-angelica lactone to isatins has been developed. With a N,N'-dioxide-Sc(OTf)3 complex as catalyst, a variety of δ-hydroxy butenolides bearing congested adjacent tetrasubstituted stereocenters were obtained in good yields with high diastereoselectivities and excellent enantioselectivities. Besides, a possible transition state was proposed to explain the origin of the asymmetric induction.

Enantioselective construction of branched 1,3-dienyl substituted quaternary carbon stereocenters by asymmetric allenyl Claisen rearrangement.

The availability of enantiomerically enriched 1,3-dienyl substituted quaternary stereocenters is highly valuable for the synthesis of complex natural compounds. Despite great advances in the area of construction of alkenyl-substituted types, a general, practical catalytic system that works for enantioselective formation of 1,3-diene derivatives still remains to be developed. Herein, we disclose the first asymmetric Claisen rearrangement of allenyl vinyl ethers to access optically active ß-ketoesters, containing branched 1,3-butadienyl substituted stereocenters. A variety of substrates bearing a range of useful functional groups were well tolerated, thus affording the corresponding products with excellent enantioselectivities (up to 99% ee) and high yields (up to 91%).

Kinetic Resolution of 2H-Azirines by Asymmetric Imine Amidation.

Highly efficient kinetic resolution of 2H-azirines by an asymmetric imine amidation was achieved in the presence of a chiral N,N'-dioxide/Sc(III) complex, thus providing a promising method to obtain the enantioenriched 2H-azirine derivatives and protecting-group free aziridines at the same time. It is rare to find an example of N1 of an oxindole participating in a reaction over C3. Moreover, chiral 2H-azirines were stereospecifically transformed into an unprotected aziridine and α-amino ketone.

Synergistic Kinetic Resolution and Asymmetric Propargyl Claisen Rearrangement for the Synthesis of Chiral Allenes.

The asymmetric propargyl Claisen rearrangement provides a convenient entry to chiral allene motifs. Herein, we describe the development of a kinetic resolution and asymmetric rearrangement of racemic propargyl vinyl ethers. This transformation afforded chiral allene products along with the enantiomerically enriched substrate in good yields with excellent diastereo- and enantioselectivity. The complete chirality transfer and facially selective rearrangement enabled the simultaneous construction of an axially chiral allenic unit and a quaternary carbon stereocenter.

Possible association of killer cell immunoglobulin-like receptor genotypes and haplotypes with dry eye disease in a Han Chinese population.

PURPOSE: The objective of this study was to explore whether killer immunoglobulin-like receptor (KIR) genotypes and haplotypes are associated with dry eye disease (DED) in a Han Chinese population. METHODS: Polymerase chain reaction with sequence-specific primers (PCR-SSP) method was used to genotype KIR genes in 106 patients with DED and 220 healthy controls. RESULTS: Twenty-three KIR genotypes were observed in the DED patient and healthy control groups, ten of which had not been described previously. The genotype G and haplotype 4 were associated with increased risk of DED, and the odds ratio (OR) and 95% confidence interval (95% CI) were 2.58, 1.10-6.02 and 2.48, 1.31-4.69, respectively; while haplotype 2 appeared to have an inverse association with the disease (OR, 0.64; 95% CI, 0.44-0.92). Genotype B/B was also associated with increased risk of DED, and the OR and 95% CI were 2.35 and 1.09-5.10, respectively. KIR haplotypes A and B have distinctive centromeric (Cen) and telomeric (Tel) gene-content motifs, and Cen-B/B was associated with increased risk of DED (OR, 2.38; 95% CI, 1.03-5.49). However, all frequencies of these KIR genotypes and haplotypes were no longer statistically significant between the two groups after the Bonferroni correction was applied for multiple testing. CONCLUSIONS: There was a possible association between certain KIR genotypes and haplotypes with DED in a Han Chinese population. However, additional confirmation is required.