Highly enantioselective synthesis of both enantiomers of tetrahydroquinoxaline derivatives via Ir-catalyzed asymmetric hydrogenation.

A novel Ir-catalyzed asymmetric hydrogenation protocol for the synthesis of chiral tetrahydroquinoxaline (THQ) derivatives has been developed. By simply adjusting the reaction solvent, both enantiomers of mono-substituted chiral THQs could be selectively obtained in high yields with excellent enantioselectivities (toluene/dioxane: up to 93% yield and 98% ee (R); EtOH: up to 83% yield and 93% ee (S)). For 2,3-disubstituted chiral THQs, the cis-hydrogenation products were obtained with up to 95% yield, 20 : 1 dr, and 94% ee. Remarkably, this methodology was also applicable under continuous flow conditions, yielding gram-scale products with comparable yields and enantioselectivities (dioxane: 91% yield and 93% ee (R); EtOH: 90% yield and 87% ee (S)). Unlike previously reported Ir-catalyzed asymmetric hydrogenation protocols, this system exhibited a significant improvement as it required no additional additives. Furthermore, comprehensive mechanistic studies including deuterium-labeling experiments, control experiments, kinetic studies, and density functional theory (DFT) calculations were conducted to reveal the underlying mechanism of enantioselectivities for both enantiomers.

Enhancement of zein-based films for mango preservation using high-intensity ultrasound and castor oil plasticization.

Zein-based films exhibit high efficiency in ethylene adsorption. However, its brittleness limits the practical applications. To address this issue, this study synergizes the plasticizing effects of high-intensity ultrasound (HIU) and castor oil (CO) to reduce the brittleness of zein-based films. The plasticizing mechanism was demonstrated through the formation of new intermolecular hydrogen bonds and electrostatic interactions, as evidenced by fourier transform infrared spectroscopy (FTIR) and zeta potential measurements. The tensile strength of 6 % CO-zein film increased eightfold. Additionally, the freshness of mangoes stored with 6 % CO-zein film significantly improved, extending their shelf life from 5 days to 15 days. Therefore, this study investigated the synergistic plasticization of zein-based films through the addition of CO, based on HIU. It also provides a theoretical basis for fruit packaging.

Four-step continuous-flow total synthesis of (-)-debromoflustramine B using a chiral heterogeneous Pd NP catalyst.

Various prenylated indoline alkaloids with diverse biological activities, including (-)-debromoflustramine B with significant butyrylcholinesterase inhibitory activity, could be synthesized by dearomative prenylation reactions of tryptophan derivatives. However, previously reported dearomative prenylations were limited to batch reactions at the milligram scale, requiring multistep reactions and complex post-processing to obtain the desired natural products. The more efficient synthesis of alkaloids remains challenging, as does the recovery of expensive catalysts. Herein, we developed a chiral heterogeneous Pd nanoparticle (NP) catalyst supported on a polymer, which produces indoline alkaloids in high yields with excellent enantioselectivities. Additionally, the first gram-scale four-step continuous-flow total synthesis of (-)-debromoflustramine B was successfully achieved with this chiral Pd heterogeneous catalyst, requiring only a simple post-processing step.

Effect of glycine and Pediococcus pentosaceus R1 combined application on the physicochemical properties, oxidative stability, and taste profile of Harbin dry sausages.

This study investigated the effects of the application of glycine (Gly) and Pediococcus pentosaceus R1(Pp), alone or in combination, on the physicochemical properties, oxidative stability, and taste quality of Harbin dry sausages. The results demonstrated that after nine days of fermentation, the Gly + Pp group exhibited significantly (P < 0.05) lower moisture content (19.04%), water activity (0.686), and pH (4.78) values, alongside notably (P < 0.05) higher lactic acid bacteria count (8.11 log CFU/g sausage) and redness value (17.2), compared to the other three groups (P < 0.05). In addition, the dry sausages in the Gly + Pp group exhibited the lowest peroxide value (0.34 meq/kg sausage), thiobarbituric acid reactive substances (0.46 MAD/kg sausage), and protein carbonyl content (1.26 nmol/kg protein) during fermentation, followed by the Gly group, Pp group, and control group. Electronic tongue (e-tongue) and sensory evaluations revealed that the combined treatment with P. pentosaceus R1 and Gly resulted in superior taste characteristics. Besides, partial least squares regression (PLSR) analysis illustrated that the taste qualities characterized using the e-tongue were accordant with the sensory evaluation consequences, and total free amino acids (FAAs) and organic acids contributed to the dry sausages' taste properties. In conclusion, the combined application of Gly and P. pentosaceus R1 enhanced the physicochemical properties, oxidative stability, and taste profile of Harbin dry sausages.

Role of sodium pyrophosphate and catechin in the enzymatic hydrolysis of oxidatively damaged myofibrillar protein gels in vitro: Mechanistic insights.

This study investigated the effects of sodium pyrophosphate (SPP) and catechin (C) on the in vitro enzymatic digestion of oxidatively damaged myofibrillar protein (MP) gel. The results indicated that SPP increased the ß-sheet content and the gastric digestibility of the MP gel, while C hindered the transition from α-helix to ß-sheet structure, leading to decreased digestibility. Notably, neither compound significantly affected intestinal digestibility. Furthermore, SPP and C significantly enhanced the antioxidant activity of MP gel digestion products. Notably, their synergistic hydrolysis products, simulating both gastric and gastrointestinal stages, chelated 91.4 % and 89.1 % of Fe2+ and scavenged 59.4 % and 77.6 % of hydroxyl radicals, respectively. Moreover, the final digestion products of the MP gel treated with SPP and C exhibited the highest content of negatively charged amino acids and absolute Zeta potential values. Overall, this study demonstrated that incorporating SPP and C could positively impact the digestion of oxidatively damaged MP gels.

Desymmetrization of Inert meso-Diethers through Copper-Catalyzed Asymmetric Allylic Alkylation with Grignard Reagents.

We have developed a highly regio-, diastereo-, and enantioselective Cu-catalyzed desymmetrization of inert meso-diethers using Grignard reagents. Moreover, previous inaccessible sterically hindered organometallic reagents are realized in the reaction with broad secondary alkyl Grignard reagents. Finally, detailed control experiments and density functional theory calculations revealed the desymmetrization of meso-diethers exploits a direct anti-SN2' pathway, in the absence of an in situ-generated allyl bromine intermediate. The following oxidative addition is the crucial rate-determining and enantioselectivity-determining step.

Distinct effects of phyllosphere and rhizosphere microbes on invader Ageratina adenophora during its early life stages.

Microbes strongly affect invasive plant growth. However, how phyllosphere and rhizosphere soil microbes distinctively affect seedling mortality and growth of invaders across ontogeny under varying soil nutrient levels remains unclear. In this study, we used the invader Ageratina adenophora to evaluate these effects. We found that higher proportions of potential pathogens were detected in core microbial taxa in leaf litter than rhizosphere soil and thus leaf inoculation had more adverse effects on seed germination and seedling survival than soil inoculation. Microbial inoculation at different growth stages altered the microbial community and functions of seedlings, and earlier inoculation had a more adverse effect on seedling survival and growth. The soil nutrient level did not affect microbe-mediated seedling growth and the relative abundance of the microbial community and functions involved in seedling growth. The effects of some microbial genera on seedling survival are distinct from those on growth. Moreover, the A. adenophora seedling-killing effects of fungal strains isolated from dead seedlings by non-sterile leaf inoculation exhibited significant phylogenetic signals, by which strains of Allophoma and Alternaria generally caused high seedling mortality. Our study stresses the essential role of A. adenophora litter microbes in population establishment by regulating seedling density and growth.

Neferine inhibits BMECs pyroptosis and maintains blood-brain barrier integrity in ischemic stroke by triggering a cascade reaction of PGC-1α.

Blood-brain barrier disruption is a critical pathological event in the progression of ischemic stroke (IS). Most studies regarding the therapeutic potential of neferine (Nef) on IS have focused on neuroprotective effect. However, whether Nef attenuates BBB disruption during IS is unclear. We here used mice underwent transient middle cerebral artery occlusion (tMCAO) in vivo and bEnd.3 cells exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) injury in vitro to simulate cerebral ischemia. We showed that Nef reduced neurobehavioral dysfunction and protected brain microvascular endothelial cells and BBB integrity. Molecular docking, short interfering (Si) RNA and plasmid transfection results showed us that PGC-1α was the most binding affinity of biological activity protein for Nef. And verification experiments were showed that Nef upregulated PGC-1α expression to reduce mitochondrial oxidative stress and promote TJ proteins expression, further improves the integrity of BBB in mice. Intriguingly, our study showed that neferine is a natural PGC-1α activator and illustrated the mechanism of specific binding site. Furthermore, we have demonstrated Nef reduced mitochondria oxidative damage and ameliorates endothelial inflammation by inhibiting pyroptosis to improve BBB permeability through triggering a cascade reaction of PGC-1α via regulation of PGC-1α/NLRP3/GSDMD signaling pathway to maintain the integrity of BBB in ischemia/reperfusion injury.

Copper-catalyzed asymmetric allylic substitution of racemic/meso substrates.

The synthesis of enantiomerically pure compounds is a pivotal subject in the field of chemistry, with enantioselective catalysis currently standing as the primary approach for delivering specific enantiomers. Among these strategies, Cu-catalyzed asymmetric allylic substitution (AAS) is significant and irreplaceable, especially when it comes to the use of non-stabilized nucleophiles (pK a > 25). Although Cu-catalyzed AAS of prochiral substrates has also been widely developed, methodologies involving racemic/meso substrates are highly desirable, as the substrates undergo dynamic processes to give single enantiomer products. Inspired by the pioneering work of the Alexakis, Feringa and Gennari groups, Cu-catalyzed AAS has been continuously employed in deracemization and desymmetrization processes for the synthesis of enantiomerically enriched products. In this review, we mainly focus on the developments of Cu-catalyzed AAS with racemic/meso substrates over the past two decades, providing an explicit outline of the ligands employed, the scope of nucleophiles, the underlying dynamic processes and their practical applications.

Advanced ethylene-absorbing and cushioning depending on the 3D porous-structured fruit packaging: Toward polyurethane foam manipulation using zein and soybean oil polyol substrates.

Fruits are essential sources of nutrients in our daily diet; however, their spoilage is often intensified by mechanical damage and the ethylene phytohormone, resulting in significant economic losses and exacerbating hunger issues. To address these challenges, this study presented a straightforward in situ synthesis protocol for producing Z/SOPPU foam, a 3D porous-structured fruit packaging. This innovative packaging material offered advanced ethylene-adsorbing and cushioning capabilities achieved through stirring, heating, and standing treatments. The results demonstrated that the Z/SOPPU foam, with its porous structure, served as an excellent packaging material for fruits, maintaining the intact appearance of tomatoes even after being thrown 72 times from a height of 1.5 m. Additionally, it exhibited desirable hydrophobicity (contact angle of 114.31 ± 0.82°), degradability (2.73 ± 0.88 % per 4 weeks), and efficient ethylene adsorption (adsorption rate of 13.2 ± 1.7 mg/m3/h). These remarkable characteristics could be attributed to the unique 3D micron-porous configuration, consisting of soybean oil polyol polyurethane foam for mechanical strain cushioning and zein for enhanced ethylene adsorption efficiency. Overall, this research offers an effective and original approach to the rational design and fabrication of advanced bio-based fruit packaging.

Effects of soaking glutinous sorghum grains on physicochemical properties of starch.

Glutinous sorghum grains were soaked (60-80 °C, 2-8 h) to explore the effects of soaking, an essential step in industrial processing of brewing, on starch. As the soaking temperature increased, the peak viscosity and crystallinity of starch gradually decreased, while the enzymatic hydrolysis rate and storage modulus first increased and then decreased. At 70 °C, the content of amylose, the enzymatic hydrolysis rate of starch, and the final viscosity first increase and then decrease with the increase of soaking time, reaching their maximum at 6 h, increased by 53.1 %, 11.0 %, and 10.4 %, respectively, as compared with the non-soaked sample. At 80 °C (4 h), the laser confocal microscopy images showed a network structure formed between the denatured protein chains and the leached-out amylose chains. The molecular weights of starch before and after soaking were all in the range of 3.82-8.98 × 107 g/mol. Since 70 °C is lower than that of starch gelatinization and protein denaturation, when soaking for 6 h, the enzymatic hydrolysis rate of starch is the highest, and the growth of miscellaneous bacteria is inhibited, which is beneficial for subsequent processing technology. The result provides a theoretical basis for the intelligent control of glutinous sorghum brewing.

Recent advances and applications in high-throughput continuous flow.

High-throughput continuous flow technology has emerged as a revolutionary approach in chemical synthesis, offering accelerated experimentation and improved efficiency. With the aid of process analytical technology and automation, this system not only enables rapid optimisation of reaction conditions at the millimole to the picomole scale, but also facilitates automated scale-up synthesis. It can even achieve the self-planning and self-synthesis of small drug molecules with artificial intelligence incorporated in the system. The versatility of the system is highlighted by its compatibility with both electrochemistry and photochemistry, and its significant applications in organic synthesis and drug discovery. This highlight summarises its recent developments and applications, emphasising its significant impact on advancing research across multiple disciplines.

The effects of resonance acoustic mixing modulation on the structural and emulsifying properties of pea protein isolate.

The effects of resonant acoustic mixing (RAM) with different treatment times (0, 5, 10, 15, 20 and 30 min) on the structural and emulsifying properties of pea protein isolate (PPI) were investigated for the first time. Increasing the RAM treatment time from 0 to 20 min decreased the α-helix/ß-sheet ratio and particle size of the PPI samples by 37.84 % and 46.44 %, respectively, accompanied by an increase in solubility from 54.79 % to 71.80 % (P < 0.05). Consequently, the emulsifying activity index of PPI (from 10.45 m2/g to 14.2 m2/g) and the physical stability of RAM-PPI emulsions were effectively enhanced, which was confirmed by the small and uniformly distributed oil droplets in the micrographs of the emulsions. However, excessive RAM treatment (30 min) diminished the effectiveness of the aforementioned improvements. Therefore, obviously enhanced solubility and emulsifying properties of PPI can be attained through proper RAM treatment (15-20 min).

Magnetic resonance imaging-based Classifications for Symptom of Adenomyosis.

OBJECTIVES: To identify an optimal magnetic resonance imaging (MRI)-based classification for the severity of adenomyosis and explore the factors associated with disease severity (dysmenorrhea or menorrhagia). DESIGN AND PARTICIPANTS: Several classifications based on MRI have been proposed, and their phenotypes are reported to be associated with the severity of adenomyosis. However, a consensus classification based on MRI findings has not yet been reached. Our study was designed to retrospectively analyze data from a cohort of patients in the Affiliated Nanchong Central Hospital of North Sichuan Medical College from June 2017 to December 2021 before focused ultrasound ablation surgery (FUAS), to identify the optimal classification of adenomyosis severity from different classification criteria and explore factors associated with the presence of symptoms. METHODS: The proportions of disease severity among different classification groups were compared to obtain the one generating the most considerable chi-square value, which was identified as the optimal classification for informing disease severity. A logistic regression model was constructed to explore factors associated with disease severity. RESULTS: Classification of Kobayashi H (classification 4) concerning the affected areas and size (volumes of lesions) was recognized as the optimal one, which identified dysmenorrhea (χ2=18.550, p-value=0.002) and menorrhagia (χ2=15.060, p-value=0.010) secondary to adenomyosis. For volumes of uterine wall <2/3, the dysmenorrhea rate in subtype-4 was higher than that in subtype-1 (χ2=4.114, p-value=0.043), and the dysmenorrhea rate in subtype-5 was higher than that in subtype-2 (χ2=4.357, p-value=0.037). Age (OR=0.899, 95%CI=0.810～0.997, p-value=0.044) and external phenotype (OR=3.588, 95%CI=CI 1.018～12.643, p-value=0.047) were associated with dysmenorrhea. Concerning volumes of uterine wall ≥2/3, the menorrhagia rate in subtype-3 remarkably increased compared with that in subtype-6 (χ2=9.776, p-value=0.002), and internal phenotype was identified as an independent factor associated with menorrhagia (OR=1.706, 95%CI=1.131～2.573, p-value=0.011). LIMITATIONS: Patients in our study were all included before FUAS, which limited our result interpretation for the general patient population. CONCLUSIONS: MRI-based classification 4 is identified as an optimal classification for informing the severity of adenomyosis. The phenotype of classification is the main characteristic associated with disease severity.

A novel selective ERK1/2 inhibitor, Laxiflorin B, targets EGFR mutation subtypes in non-small-cell lung cancer.

Extracellular regulated protein kinases 1/2 (ERK1/2) are key members of multiple signaling pathways, including the ErbB axis. Ectopic ERK1/2 activation contributes to various types of cancer, especially drug resistance to inhibitors of RTK, RAF and MEK, and specific ERK1/2 inhibitors are scarce. In this study, we identified a potential novel covalent ERK inhibitor, Laxiflorin B, which is a herbal compound with anticancer activity. However, Laxiflorin B is present at low levels in herbs; therefore, we adopted a semi-synthetic process for the efficient production of Laxiflorin B to improve the yield. Laxiflorin B induced mitochondria-mediated apoptosis via BAD activation in non-small-cell lung cancer (NSCLC) cells, especially in EGFR mutant subtypes. Transcriptomic analysis suggested that Laxiflorin B inhibits amphiregulin (AREG) and epiregulin (EREG) expression through ERK inhibition, and suppressed the activation of their receptors, ErbBs, via a positive feedback loop. Moreover, mass spectrometry analysis combined with computer simulation revealed that Laxiflorin B binds covalently to Cys-183 in the ATP-binding pocket of ERK1 via the D-ring, and Cys-178 of ERK1 through non-inhibitory binding of the A-ring. In a NSCLC tumor xenograft model in nude mice, Laxiflorin B also exhibited strong tumor suppressive effects with low toxicity and AREG and EREG were identified as biomarkers of Laxiflorin B efficacy. Finally, Laxiflorin B-4, a C-6 analog of Laxiflorin B, exhibited higher binding affinity for ERK1/2 and stronger tumor suppression. These findings provide a new approach to tumor inhibition using natural anticancer compounds.

Highly enantioselective synthesis of both tetrahydroquinoxalines and dihydroquinoxalinones via Rh-thiourea catalyzed asymmetric hydrogenation.

Chiral tetrahydroquinoxalines and dihydroquinoxalinones represent the core structure of many bioactive molecules. Herein, a simple and efficient Rh-thiourea-catalyzed asymmetric hydrogenation for enantiopure tetrahydroquinoxalines and dihydroquinoxalinones was developed under 1 MPa H2 pressure at room temperature. The reaction was magnified to the gram scale furnishing the desired products with undamaged yield and enantioselectivity. Application of this methodology was also conducted successfully under continuous flow conditions. In addition, 1H NMR experiments revealed that the introduction of a strong Brønsted acid, HCl, not only activated the substrate but also established anion binding between the substrate and the ligand. More importantly, the chloride ion facilitated heterolytic cleavage of dihydrogen to regenerate the active dihydride species and HCl, which was computed to be the rate-determining step. Further deuterium labeling experiments and density functional theory (DFT) calculations demonstrated that this reaction underwent a plausible outer-sphere mechanism in this new catalytic transformation.

Interaction with wheat starch affect the aggregation behavior and digestibility of gluten proteins.

Understanding the interplay between gluten and wheat starch is crucial for elucidating the digestibility mechanism of gluten in wheat-based products. However, this mechanism remains under-investigated. This study sought to elucidate the influence of starch-induced protein structural modifications on gluten digestion. Our findings revealed that starch considerably enhanced gluten digestion. In the presence of starch, gluten protein digestibility increased from 10.91 % (in the control group with a gluten-to-starch ratio of 1:0) to 14.40 % (in the complex with a gluten-to-corn starch ratio of 1:1). The diminished gluten protein digestibility due to starch may be ascribed to modifications in protein configuration and aggregation behavior. Morphological studies suggested that starch not only functioned as filler particles but also diluted the gluten matrix. A protein network assessment further affirmed that both the junction density and branching rate of gluten proteins decreased notably by 29.9 % and 25.1 %, respectively. Conversely, lacunarity increased by 1.92-fold, compromising the cohesiveness and connectivity of the gluten matrix. Elevated starch concentrations suppressed the formation of disulfide bonds, impeding gluten protein aggregation. Concurrently, gluten-starch interactions were governed by hydrogen bonds and hydrophobic associations. In summary, starch augmented gluten protein digestibility by curtailing their polymerization. This revelation might offer novel perspectives on optimizing gluten protein digestion and utilization.

Molecular mechanisms affecting the stability of high internal phase emulsions of zein-soy isoflavone complexes fabricated with ultrasound-assisted dynamic high-pressure microfluidization.

In this study, zein-soy isoflavone complex (ZSI) emulsifiers were fabricated using ultrasound-assisted dynamic high-pressure micro fluidization to stabilise highinternal phase pickering emulsions. Ultrasound-assisted dynamic high-pressure micro-fluidization enhanced surface hydrophobicity, zeta potential, and soy isoflavone binding capacity, while it decreased particle size, especially during ultrasound and subsequent microfluidization. The treated ZSI could produce small droplet clusters and gel-like structures, with excellent viscoelasticity, thixotropy and creaming stability owing to their neutral contact angles. Ultrasound and subsequent micro fluidization treatment of the ZSI complexes were highly effective in preventing droplet flocculation and coalescence after long-term storage or centrifugation due to their higher surface load, thicker multi-layer interfacial structure, and stronger electronic repulsion between the oil droplets. This study provides insights and extends our current knowledge of how non-thermal technology affects the interfacial distribution of plant based particles and the physical stability of emulsions.

Coagulation after paediatric miniaturised versus conventional cardiopulmonary bypass: Retrospective cohort study.

BACKGROUND: Cardiopulmonary bypass (CPB) causes coagulation disorders after surgery. This study aimed to compare the coagulation parameters after congenital cardiac surgery with miniaturised CPB (MCPB) versus conventional CPB (CCPB). METHODS: We gathered information about children who underwent cardiac surgery between 1/1/2016 and 12/31/2019. Using propensity score-matched data, we compared the coagulation parameters and postoperative outcomes of the MCPB and CCPB groups. RESULTS: A total of 496 patients (327 with MCPB, 169 withCCPB) underwent congenital cardiac surgery, and 160 matched pairs in each group were enrolled in the analysis. Compared with CCPB children, MCPB children had a lowermean prothrombin time (14.9 ± 2.0 vs 16.4 ± 4.1; p < 0.001)and international normalised ratio (1.3 ± 0.2 vs. 1.4 ± 0.3; p < 0.001), but higher thrombin time (23.4 ± 20.4 vs 18.2 ± 4.4; p = 0.002). The CCPB group had greaterperioperative changes inprothrombin time, international normalised ratio, fibrinogen, and antithrombin III activity (all p < 0.01) but lower perioperative changesin thrombin time (p = 0.001) thanthe MCPB group. Ultra-fasttrack extubation and blood transfusionrates, postoperative blood loss, and intensive care unitlength of stay were considerably decreased in the MCPB group. There were no considerable intergroup differences in the activated partial thromboplastin time or platelet count. CONCLUSIONS: Compared with CCPB, MCPB was associated with lower coagulation changes and better early outcomes, including shorter intensive care unit stay and less postoperative blood loss.

Copper-catalyzed asymmetric allylic alkylation of racemic inert cyclic allylic ethers under batch and flow conditions.

Highly enantioselective Cu-catalyzed asymmetric allylic alkylation of racemic inert cyclic allylic ethers is accomplished in this work. The use of Grignard reagents in combination with BF3·OEt2 and CuBr·SMe2/L2 is the key to enable employment of long-challenging low reactive allylic substrates in this AAA reaction. In addition, the approach exhibited a remarkable superiority in the construction of a stereogenic center involving challenging sterically hindered nucleophiles for both primary and secondary alkyl groups. Extension of this method under continuous flow conditions was also performed with excellent enantioselectivity in a short residence time. Mechanistic experiments indicated that the reaction proceeded through an in situ generated allylic bromide intermediate. All these advantages demonstrated that this chiral catalytic system is a valuable complement for existing asymmetric catalytic methods.