Modular Access to Chiral Amines via Imine Reductase-Based Photoenzymatic Catalysis.

The development of catalysts serves as the cornerstone of innovation in synthesis, as exemplified by the recent discovery of photoenzymes. However, the repertoire of naturally occurring enzymes repurposed by direct light excitation to catalyze new-to-nature photobiotransformations is currently limited to flavoproteins and keto-reductases. Herein, we shed light on imine reductases (IREDs) that catalyze the remote C(sp3)-C(sp3) bond formation, providing a previously elusive radical hydroalkylation of enamides for accessing chiral amines (45 examples with up to 99% enantiomeric excess). Beyond their natural function in catalyzing two-electron reductive amination reactions, upon direct visible-light excitation or in synergy with a synthetic photoredox catalyst, IREDs are repurposed to tune the non-natural photoinduced single-electron radical processes. By conducting wet mechanistic experiments and computational simulations, we unravel how engineered IREDs direct radical intermediates toward the productive and enantioselective pathway. This work represents a promising paradigm for harnessing nature's catalysts for new-to-nature asymmetric transformations that remain challenging through traditional chemocatalytic methods.

Effects of the Hydroxy-Regulated Li-Montmorillonite Atomic Interface Arrangement on Li Cycle of Marine Sedimentation and pH.

The reaction of ubiquitous clay is related to the global cycle of the key metals, but the relationship between the Li occurrence interface and the sedimentation in the Li cycle remains unclear. We investigated the atomic interface arrangement of Li-montmorillonite (Li-Mt) during low-temperature water-rock reactions and Li migration. The results show that, in Cl-rich systems, deprotonation and exposure of Na adsorption sites cause Li enrichment and O pairing, which lead to the weakening of the shielding effect of Mt on anions and the formation of a Mt-Li-Cl atomically interfacial arrangement. Only up to 20.3% of the Li is contained in the atomic interface of Li-Mt. In F-rich system, the dehydroxylation of F paired with Al in octahedral sites causes Li accumulation via local crystallization of LiF, and co-complexation of F and Li forms a Mt(Al)-F-Li atomic interface, in which up to 46.8% of the Li is enriched by the Mt. The participation of F and Cl in the complexation intensifies lattice collapse of the Li-Mt edge. The sedimentation velocity decreases with the smaller particle size affected by the Li loading. Lithium leached from igneous rocks serves as the marine Li source, which contributes up to 99.8% and 99.5% of the Li in Cl- and F-rich systems, respectively. The response of Mt(OH) to Li migration with a time accumulating effect may make an important regulatory of oceanic pH by either acidification or alkalization.

Diterpenoids from Euphorbia peplus possessing cytotoxic and anti-inflammatory activities.

Phytochemical investigation into the medium polar fraction of the ethanol extract of Euphorbia peplus led to the identification of 32 diterpenoids with five structural types. Compounds 1-5 and 7-11 are reported for the first time, while the configuration of 6,7-epoxy group of 6 was revised to be ß-oriented. Compounds 1-5 feature a rare structural variation of the double bond at Δ1 migrating to Δ1(10) in the tigliane-type diterpenoid family. Biologically, compound 21 was found to be the only one to show moderate cytotoxic activity, associated with the presence of a benzoyloxy residue at C-16. Besides, compounds 4, 8, 12, 13, 16, and 19 show significant inhibitory activities against NO production induced by LPS in RAW264.7 macrophage cells, with IC50 values within 2-5 µM. Structure-activity relationship (SAR) analysis revealed that the ingenane-type diterpenoids have the best anti-inflammatory activity, and the esterification at 3-OH or 5-OH is crucial. Further biological researches demonstrated that 13, the predominant metabolite in this plant, exerts anti-inflammatory effects by blocking the activation of NF-κB and MAPK signaling pathways.

Repurposing Visible-Light-Excited Ene-Reductases for Diastereo- and Enantioselective Lactones Synthesis.

Repurposing enzymes to catalyze non-natural asymmetric transformations that are difficult to achieve using traditional chemical methods is of significant importance. Although radical C-O bond formation has emerged as a powerful approach for constructing oxygen-containing compounds, controlling the stereochemistry poses a great challenge. Here we present the development of a dual bio-/photo-catalytic system comprising an ene-reductase and an organic dye for achieving stereoselective lactonizations. By integrating directed evolution and photoinduced single electron oxidation, we repurposed engineered ene-reductases to steer non-natural radical C-O formations (one C-O bond for hydrolactonizations and lactonization-alkylations while two C-O bonds for lactonization-oxygenations). This dual catalysis gave a new approach to a diverse array of enantioenhanced 5- and 6-membered lactones with vicinal stereocenters, part of which bears a quaternary stereocenter (up to 99 % enantiomeric excess, up to 12.9 : 1 diastereomeric ratio). Detailed mechanistic studies, including computational simulations, uncovered the synergistic effect of the enzyme and the externally added organophotoredox catalyst Rh6G.

Mechanisms of Lithium Enrichment and Metallogenesis in a Simulated Montmorillonite-Fluid System.

Due to strong industrial demand for Li, Li-bearing montmorillonite (Li-Mt) deposits are a focus for exploration, but the Li enrichment mechanisms in such deposits are unclear. In this study, adsorption experiments and mineralogical analyses were used to investigate the water-rock reactions at different Li concentrations, temperatures, durations, and pH conditions, in order to reveal the Li enrichment mechanisms in F- and Cl-rich systems. Our results suggest that water-rock reactions are different in the two halogen systems. The reaction in the LiCl-Mt system involves deprotonation, whereas dehydroxylation occurs in a LiF-Mt system. Lithium is adsorbed or exchanges with interlayer cations in Mt. Adsorption forms a monolayer that is consistent with the Langmuir model in a LiCl system. Lithium is adsorbed in multi-layers in Mt in a LiF system. For a given Li concentration, the adsorption capacity of the LiF-Mt system is 2.8 times greater than that of the LiCl-Mt system. The pH has a weaker effect in the LiCl-Mt system than in the LiF-Mt system. Furthermore, Li adsorption is hindered at very high or low pH in a LiF system. The chemical shift of Li is -0.2 ppm (±0.1 ppm) in a nuclear magnetic resonance (NMR), which indicates that Li occurs as inner-sphere complexes in the pseudo-hexagonal cavity in Mt. Based on a CaCl2 leaching experiment, >50% (up to 97.94%) of the Li can be easily exchanged out of the Mt. The residual Li in the inner-sphere is the key to metallogenesis of Li-Mt deposits. Therefore, the grade of ion adsorption-type Li deposits is determined by the exchangeable Li.

Preparation of pH-responsive reversible wettable surfaces and application for oil-water separation.

With the continuous development of society, the discharge of oily wastewater in daily life and industry has gradually increased, causing considerable damage to the environment, and how to effectively treat oily wastewater is an urgent problem. In this paper, a simple method is proposed to prepare superhydrophobic stainless steel mesh with pH response. The relationship between the ratio of mixed thiols and the surface wettability was explored, as well as the morphology, chemical composition, and pH-responsive mechanism of the stainless steel mesh surface were analyzed, and the separation efficiency, recycling ability, and backwashing ability of the mesh were explored by oil-water separation experiments. It was found that when the molar fraction of 11-mercaptoundecanoic acid and 1-decanethiol in the mixed mercaptan was 2:3, the water contact angle of the surface at this point was 156.5 ± 1°, with pH response characteristics and good oil-water separation efficiency, backwashing and recycling capabilities.

Factors contributing to rill erosion of forest roads in a mountainous watershed.

Forest roads are a major source of and transport pathway for eroded sediments in mountainous watersheds. When rills develop on these roads' surfaces, they amplify sediment erosion. Best management practices can decrease sediment erosion, but in order to efficiently implement these practices it is necessary to determine which factors have the most influence on rill development on forest roads. Despite this need, there is scarce literature on rill development on forest roads. To fill this gap in knowledge, based on field survey and multivariate statistical methods including redundancy analysis (RDA) and variation partitioning analysis (VPA), we investigated unpaved forest roads in the Xiangchagou watershed in China and quantified the extent to which various factors influenced rill formation. Specifically, we studied how rill erosion intensity (REI) and rill morphological characteristics (like rill length, mean width and depth, density, and severity of fragmentation) varied along the slope of a forest road. We also introduced the concept of a road's hydrological constituents (its upslope catchment, surface, and cutslopes), and determined how much each constituent contributed to REI. We found that REI and morphological characteristics decreased moving from the upper portion of road segment downward, implying that rills developed more intensely uphill. Additionally, REI increased exponentially with rill width, density, and severity of fragmentation, and increase linearly with length and depth. Conversely, REI decreased exponentially with rill width-depth ratio. These relationships suggest that the morphological characteristics of rills could be used to predict the REI of a given road segment. Finally, we found that the road characteristics that best predicted rill formation included catchment area, cutslope area, and gravel bareness. Correspondingly, the upslope catchment, cutslopes, and road surface contributed 11.56%, 30.83%, and 8.23% of the variation in REI and morphological characteristics. The interaction between upslope catchment and road surface explained 19.89% of the variation. These results suggest that when best management practices are implemented to decrease erosion caused by forest roads in mountainous watersheds, they should integrate these hydrological constituents of a road.

Long non-coding RNA FOXP4-AS1 facilitates the biological functions of hepatocellular carcinoma cells via downregulating ZC3H12D by mediating H3K27me3 through recruitment of EZH2.

BACKGROUND: Some studies have reported the effect of long non-coding RNA forkhead box P4 antisense RNA 1 (lncRNA FOXP4-AS1) on hepatocellular carcinoma (HCC). Here, we aimed to discuss the effects of FOXP4-AS1/enhancer of zeste homolog 2 (EZH2)/trimethylation of lysine 27 on histone H3 (H3K27me3)/zinc finger CCCH-type containing 12D (ZC3H12D) axis on HCC. METHODS: The expression of FOXP4-AS1, EZH2, and ZC3H12D, and abundance of H3K27me3 in HCC tissues and cells were tested. The relationship between FOXP4-AS1 expression and prognosis of HCC patients was analyzed. The biological functions of HCC cells were detected via loss- and gain-of-function assays. The tumor weight and volume in vivo were tested. The interaction between FOXP4-AS1 and EZH2 as well as that between EZH2 and H3K27me3 was verified. RESULTS: FOXP4-AS1 and EZH2 expression and H3K27me3 abundance were enhanced while ZC3H12D expression was depressed in HCC tissues and cells. Knockdown of FOXP4-AS1 suppressed biological functions of HCC cells as well as the weight and volume of HCC transplanted tumor. Depleting ZC3H12D reversed the effect of downregulated FOXP4-AS1 on HCC cells. FOXP4-AS1 suppressed ZC3H12D expression via mediating H3K27me3 by recruitment of EZH2. CONCLUSION: The key findings of the present study demonstrate that FOXP4-AS1 suppresses ZC3H12D expression via mediating H3K27me3 by recruitment of EZH2, thus promoting the progression of HCC.

Effectiveness of a combined problem-based learning and flipped classroom teaching method in ophthalmic clinical skill training.

BACKGROUND: Previous studies have primarily implemented problem-based learning (PBL) or flipped classroom (FC) teaching models in different majors; however, research on the combined PBL-FC teaching method in clinical medicine is scarce. Therefore, we investigated the combined PBL-FC teaching method in teaching ocular trauma on students' competencies. METHOD: About 75 ophthalmology postgraduates were randomly divided into PBL-FC and traditional teaching groups. Students completed pre-and post-class theoretical examinations, skills evaluation, learning ability scales, and feedback questionnaires. RESULTS: Both groups showed significantly higher theoretical scores and improved learning ability. Feedback questionnaire scores of the PBL-FC group's postgraduates without clinical experience were significantly higher than the traditional group's for some items; there was no difference between groups in postgraduates with clinical experience. PBL-FC group's pre-class preparation time was significantly longer than the traditional group's, but the post-class review time was significantly shorter. PBL-FC group's post-class theoretical performance was significantly higher than the traditional group's. There was no statistical difference between the groups regarding skill operation. Among postgraduates without clinical experience, the PBL-FC group's skill operation performance was significantly higher than the traditional group's; for postgraduates with clinical experience, the traditional group's skill operation performance was significantly higher than the PBL-FC group's. CONCLUSIONS: PBL-FC teaching is better for students without clinical experience or knowledge of ophthalmic diseases. Meanwhile, traditional teaching is a good choice for students with clinical experience who need more relevant knowledge.

Natural Enantiomers: Occurrence, Biogenesis and Biological Properties.

The knowledge that natural products (NPs) are potent and selective modulators of important biomacromolecules (e.g., DNA and proteins) has inspired some of the world's most successful pharmaceuticals and agrochemicals. Notwithstanding these successes and despite a growing number of reports on naturally occurring pairs of enantiomers, this area of NP science still remains largely unexplored, consistent with the adage "If you don't seek, you don't find". Statistically, a rapidly growing number of enantiomeric NPs have been reported in the last several years. The current review provides a comprehensive overview of recent records on natural enantiomers, with the aim of advancing awareness and providing a better understanding of the chemical diversity and biogenetic context, as well as the biological properties and therapeutic (drug discovery) potential, of enantiomeric NPs.

Bioactive sesquiterpenoids from the flower buds of Tussilago farfara.

Eleven new compounds including five bisabolane (1-5) and three oplopane (6-8) sesquiterpenoids, a pair of benzopyran enantiomers (9 & 10) and a benzofuran derivative (11), along with six known sesquiterpenoid co-metabolites (12-17), have been obtained from the flower buds of Tussilago farfara. Their structures were elucidated by comprehensive spectroscopic analyses and comparison with structurally related known analogues. The absolute configurations of all the compounds except 11 were unequivocally assigned by various techniques, including Mosher's method and time-dependent density functional theory (TD-DFT) based calculations of 13C NMR and electronic circular dichroism (ECD) data. The C-8 absolute configuration on the sidechain of this group of bisabolane sesquiterpenoids was assigned for the first time. Our bioassays have established that compounds 3, 4, 13 and 14 showed significant α-glucosidase inhibitory activities, while 6, 8 and 14 displayed moderate antiproliferative effects against two human tumor cell lines A549 and MDA-MB-231. Further flow cytometric analysis revealed that 14 effectively induced cell apoptosis and arrested cell cycle at the S/G2 phases in A549 cells, in a dose-dependent manner.

Thiophene enantiomers from the aerial parts of Eclipta prostrata.

Ten thiophene derivatives (1-10), including two previously undescribed ones (1 and 2), have been obtained and structurally characterized from the aerial parts of a traditional Chinese herb Eclipta prostrata. Six of them with one chiral center were identified to be scalemic mixtures, and the pure enantiomers of two isolates (1 and 3) were successfully separated via chemical derivatization and chiral HPLC, with the absolute configurations being established by analysis of optical rotations. All the thiophenes were subjected to a series of assays and compounds 9 and 10 exhibited mild antibacterial activity against Staphylococcus aureus.[Formula: see text].

Diarylheptanoids with NO production inhibitory activity from Amomum kravanh.

Seven new diarylheptanoids, kravanhols C-I (1-7), along with two known analogues (8 and 9), were isolated from the fruits of Amomum kravanh. The structures of compounds 1-7 were elucidated by analysis of spectroscopic data, and the absolute configurations of selective ones were determined by time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculations. All compounds were evaluated for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells. Compounds 2, 5, 6 and 9 exhibited moderate inhibitory activity with IC50 values in the range of 17.4-26.5 µM, being more potent than the positive control dexamethasone (IC50 = 32.5 µM).

Limonoids from Cipadessa baccifera.

Eighteen new limonoids, including eight methyl angolensates (1-8) and 10 cipadesins (9-18), were isolated from the leaves of Cipadessa baccifera. Their structures were characterized by means of spectroscopic data analyses, single-crystal X-ray diffraction, and quantum chemistry computational methods. The C-6 configurations in those compounds possessing a C-6 hydroxy group were all assigned as S regardless of the magnitude of J5,6, and the C-2' configuration in those bearing a 2-methylbutyryl residue was defined by single-crystal X-ray diffraction and NMR data. Compounds 1, 5, 6, 7, 11, and 12 showed moderate antimalarial activities with IC50 values ranging from 12 to 28 µM.

Efficient synthesis of γ-glutamyl compounds by co-expression of γ-glutamylmethylamide synthetase and polyphosphate kinase in engineered Escherichia coli.

γ-Glutamyl compounds have unveiled their importance as active substances or precursors of pharmaceuticals. In this research, an approach for enzymatic synthesis of γ-glutamyl compounds was developed using γ-glutamylmethylamide synthetase (GMAS) from Methylovorus mays and polyphosphate kinase (PPK) from Corynebacterium glutamicum. GMAS and PPK were co-recombined in pETDuet-1 plasmid and co-expressed in E. coli BL21 (DE3), and the enzymatic properties of GMAS and PPK were investigated, respectively. Under the catalysis of the co-expression system, L-theanine was synthesized with 89.8% conversion when the substrate molar ratio of sodium glutamate and ethylamine (1:1.4) and only 2 mM ATP were used. A total of 14 γ-glutamyl compounds were synthesized by this one-pot method and purified by cation exchange resin and isoelectric point crystallization with a yield range from 22.3 to 72.7%. This study provided an efficient approach for the synthesis of γ-glutamyl compounds by GMAS and PPK co-expression system.

Structural characterization and biological evaluation of chemical constituents from Ilex cornuta.

One new ursane-type triterpenoid (1), one new ursane-type triterpenoid glycoside (2), and one new oleanane-type triterpenoid glycoside (3), along with 20 known compounds, were isolated from the leaves of Ilex cornuta. The structures of these natural products were elucidated on the basis of detailed spectroscopic analyses and chemical derivation. Our biological evaluation established that selective compounds showed moderate to significant antioxidant activities in the 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) methods.

Two new naphthoate derivatives from Morinda officinalis.

Two new naphthoate derivatives, including a symmetrical dimer (1) and a monomer (2), were separated from the roots of Morinda officinalis var. hirsuta. Their structures were characterized on the basis of spectroscopic means especially MS and NMR methods. Biological evaluations revealed that the two compounds did not show inhibition against both cholinesterases AChE and BChE, while the dimer (1) did exhibit moderate growth inhibitory activity toward one human osteosarcoma cell line U2OS with an IC50 value of 18.5 ± 1.1 µM.

Structural Elucidation and Total Synthesis of Three 9-Norlignans from Curculigo capitulata.

Capitulactones A-C, three unprecedented 9-norlignans featuring a unique 3,5-dihydrofuro[2,3- d]oxepin-7(2 H)-one scaffold, were isolated from the roots of Curculigo capitulata. Their structures with absolute configurations were unambiguously established by a combination of spectroscopic data, ECD analysis, and total synthesis. Biomimetic total syntheses of three pairs of the corresponding enantiomers were achieved in 9-10 steps with overall yields of 14.8, 12.7, and 10.3%, respectively. Notably, the unique scaffold of the common western hemisphere of the molecules was constructed by using the oxidation-reduction strategy from benzodihydrofuran.

Germacrane-type sesquiterpenoids with cytotoxic activity from Sigesbeckia orientalis.

Eleven new highly oxygenated germacrane-type sesquiterpenoids (1-11) and 16 known analogues (12-27) were isolated from the aerial parts of Sigesbeckia orientalis. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially NMR and ECD analyses. Compounds 13, 21 and 23 possessing an 8-methacryloxy group showed stronger in vitro cytotoxicity against human A549 and MDA-MB-231 cancer cell lines than other co-metabolites, with IC50 values ranging from 6.02 to 10.77 µM comparable to the positive control adriamycin.

Chromane Enantiomers from the Flower Buds of Tussilago farfara L. and Assignments of Their Absolute Configurations.

Fourteen chromane derivatives of seven pairs of enantiomers (1-14) have been obtained from the ethanolic extract of the flower buds of Tussilago farfara L. Their structures with absolute configurations have been elucidated by detailed spectroscopic analyses, chemical methods, and particularly comparison of experimental ECD spectra with theoretically computed ones. Biological evaluations revealed that they did not show cytoprotective, antimicrobial, and α-glucosidase inhibitory activities.