Flow chemistry-enabled asymmetric synthesis of cyproterone acetate in a chemo-biocatalytic approach.

Flow chemistry has many advantages over batch synthesis of organic small-molecules in terms of environmental compatibility, safety and synthetic efficiency when scale-up is considered. Herein, we report the 10-step chemo-biocatalytic continuous flow asymmetric synthesis of cyproterone acetate (4) in which 10 transformations are combined into a telescoped flow linear sequence from commercially available 4-androstene-3, 17-dione (11). This integrated one-flow synthesis features an engineered 3-ketosteroid-Δ-dehydrogenase (ReM2)-catalyzed Δ-dehydrogenation to form the C1, C2-double bond of A ring, a substrate-controlled Co-catalyzed Mukaiyama hydration of 9 to forge the crucial chiral C17α-OH group of D ring with excellent stereoselectivity, and a rapid flow Corey-Chaykovsky cyclopropanation of 7 to build the cyclopropyl core of A ring.

LINC02418 suppresses endometrial cancer progression via regulating miR-494-3p/RASGRF1 axis.

Long non-coding RNAs (lncRNAs) have emerged as pivotal regulatory molecules in cancer biology. Among these, long intergenic non-protein coding RNA 02418 (LINC02418), a recently identified lncRNA, has been linked to endometrial cancer (EC), although its function and operational mechanisms are largely unclear. The present investigation aims to elucidate the molecular mechanism through which LINC02418 influences EC pathogenesis.

Diets supplemented with different solvents extracts of Lepista nuda alters longevity and fecundity, and the expression of related genes in Drosophila melanogaster (Diptera: Drosophilidae).

Exploring the effects of different solvent extracts from Lepista nuda [(Bull. ex Fr.) Cooke] on the lifespan and reproductive capacity of Drosophila melanogaster (Diptera: Drosophilidae), the extracts of the fruiting body and mycelium of L.

Discovery of two new long chain fatty acid esters of flavonol glycoside from Pollen Typhae Carbonisatus and their protective effects on HBMECs.

ABATRACTTwo new compounds, namely, isorhamnenin-3--neohesperidin-6''-linoleic acid ester () and isorhamnenin-3--neohesperidin-6''-palmitate (), along with 17 known compounds, were isolated from Pollen Typhae Carbonisatus (PTC). Their structures were elucidated on the basis of one-dimensional (1D)-, two-dimensional (2D)-nuclear magnetic resonance (NMR), and high-resolution electrospray ionization mass spectrometry (HRESIMS) spectroscopic data analyses. The two new compounds ( and ) exhibited a protective effect in a dose-dependent manner and promoted tube generation in the oxygen-glucose deprivation/reoxygenation (OGD/R)-induced human brain microvascular endothelial cells (HBMECs).

Leidenfrost Effect-Induced Chaotic Vortex Flow for Efficient Mixing of Highly Viscous Droplets.

Efficiently mixing highly viscous liquids in microfluidic systems is appealing for green chemistry such as chemical synthesis and catalysis, but it is a long-standing challenge owing to the unfavorable diffusion kinetics. In this work, a new strategy is explored for mixing viscous droplets by harnessing a peculiar Leidenfrost state, where the substrate temperature is above the boiling point of the liquid without apparent liquid evaporation. Compared to the control experiment where the droplet stays at a similar temperature but in the contact boiling regime, the mixing time can be reduced significantly.

Cascade Synthesis of Fe-N-Fe Dual-Atom Catalysts for Superior Oxygen Catalysis.

Dual-atom catalysts (DACs) have been proposed to break the limitation of single-atom catalysts (SACs) in the synergistic activation of multiple molecules and intermediates, offering an additional degree of freedom for catalytic regulation. However, it remains a challenge to synthesize DACs with high uniformity, atomic accuracy, and satisfactory loadings. Herein, we report a facile cascade synthetic strategy for DAC via precise electrostatic interaction control and neighboring vacancy construction.

Highly enantio- and diastereoselective construction of spirocyclic oxindoles a palladium-catalyzed decarboxylative asymmetric [4 + 2] annulation strategy.

A palladium-catalyzed decarboxylative asymmetric [4 + 2] annulation of methyleneindolinones with a zwitterionic oxo-1,4-dipole intermediate was successfully developed to access spirocyclic oxindoles bearing two vicinal stereocenters in good yields with high diastereoselectivities and enantioselectivities. This strategy features a broad substrate scope (28 examples), allowing for efficient scale-up. Further selective transformation of the product and preliminary mechanistic studies were conducted.

Taste alterations in patients following hematopoietic stem cell transplantation: A qualitative study.

Objective: This study aims to explore the experiences and consequences of taste alterations in patients undergoing HSCT, how they respond to these changes, and the factors that influence their responses.

Methods: In this descriptive qualitative study, face-to-face semi-structured individual interviews were conducted with 31 patients undergoing HSCT in a comprehensive hospital in Hubei, China. The interview data were transcribed and analyzed using Colaizzi's seven-step analysis.

Sex differences in comorbidities and mortality risk among patients with chronic obstructive pulmonary disease: a study based on NHANES data.

Background: Patients with chronic obstructive pulmonary disease (COPD) commonly have coexisting comorbidities that contribute to higher exacerbation frequency, poorer health status, and increased all-cause mortality; however, there are only a few studies available on the sex discrepancy in the comorbidity distribution and outcomes among COPD patients, and there is limited information about the discrepancy in all-cause mortality between men and women.

Methods: Based on data from the U.S.

Divergent Chemo- and Biocatalytic Route to 16β-Methylcorticoids: Asymmetric Synthesis of Betamethasone Dipropionate, Clobetasol Propionate, and Beclomethasone Dipropionate.

16β-Methylcorticoids are among the most important glucocorticoid steroids for the treatment of various dermatological disorders, respiratory infections, and other allergic reactions elicited during inflammatory responses of the human body. Betamethasone dipropionate, clobetasol propionate, and beclomethasone dipropionate are particularly noteworthy for their synthetic intractability. Despite five decades of research, these 16β-methylcorticoids have remained challenging synthetic targets owing to insurmountable issues of reactivity, selectivity, and cost efficiency associated with all previously explored strategies.

Epidemiology, genetic characteristics, and association with meteorological factors of human metapneumovirus infection in children in southern China: A 10-year retrospective study.

Objectives: This study aimed to determine the epidemiological and genetic features of human metapneumovirus (HMPV) infection in children in southern China, and the effect of meteorological factors on infection.

Methods: 14,817 children (≤14 years) with acute respiratory tract infections from 2010 to 2019 were examined for HMPV and other respiratory viruses by real-time quantitative polymerase chain reaction. Full-length F gene of 54 positive samples were sequenced and subjected to phylogenetic analysis.

Brain-derived neurotrophic factor and nerve growth factor expression in endometriosis: A systematic review and meta-analysis.

Endometriosis is diagnosed by laparoscopic surgery. The availability of biomarkers can help understand the pathophysiology and aid in the diagnosis of the condition. In this context, this review aimed to examine levels of expression of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are increased amongst patients with endometriosis and if they can serve as a potential biomarker.

Interfacial Electron Regulation and Composition Evolution of NiFe/MoC Heteronanowire Arrays for Highly Stable Alkaline Seawater Oxidation.

In alkaline seawater electrolysis, the oxygen evolution reaction (OER) is greatly suppressed by the occurrence of electrode corrosion due to the formation of hypochlorite. Herein, a catalyst consisting of MoC nanowires modified with NiFe alloy nanoparticles (NiFe/MoC) on nickel foam (NF) is prepared. The optimized catalyst can deliver a large current density of 500 mA cm at a very low overpotential of 366 mV in alkaline seawater, respectively, outperforming commercial IrO .

Rapid production of kilogram-scale graphene nanoribbons with tunable interlayer spacing for an array of renewable energy.

Graphene nanoribbons (GNRs) are widely recognized as intriguing building blocks for high-performance electronics and catalysis owing to their unique width-dependent bandgap and ample lone pair electrons on both sides of GNR, respectively, over the graphene nanosheet counterpart. However, it remains challenging to mass-produce kilogram-scale GNRs to render their practical applications. More importantly, the ability to intercalate nanofillers of interest within GNR enables in-situ large-scale dispersion and retains structural stability and properties of nanofillers for enhanced energy conversion and storage.

Chiral spirosiladiphosphines: ligand development and applications in Rh-catalyzed asymmetric hydrosilylation/cyclization of 1,6-enynes with enhanced reactivity.

Spirodiphosphines have been successfully applied in various asymmetric catalytic transformations. However, controlling the coordinating conformations by the direct displacement of the spiro atom remains elusive. Herein, we report the application of Si-centered spirodiphosphine (Si-SDP) ligands in the enantioselective hydrosilylation/cyclization of 1,6-enynes.

Host factor DUSP5 potently inhibits dengue virus infection by modulating cytoskeleton rearrangement.

Cytoskeleton has been reported to play an essential role in facilitating the viral life cycle. However, whether the host can exert its antiviral effects by modulating the cytoskeleton is not fully understood. In this study, we identified that host factor DUSP5 was upregulated after dengue virus (DENV) infection.

Effect of zearalenone on aflatoxin B1-induced intestinal and ovarian toxicity in pregnant and lactating rats.

Aflatoxin B1 (AFB1) and zearalenone (ZEN) cause serious damage to mammals, but few studies have investigated the impacts of these toxins on pregnant and lactating mammals. This study investigated the effects of ZEN on AFB1-induced intestinal and ovarian toxicity in pregnant and lactating rats. Based on the results, AFB1 reduces the digestion, absorption, and antioxidant capacity in the intestine, increases intestinal mucosal permeability, destroys intestinal mechanical barriers, and increases pathogenic bacteria' relative abundances.

Robust ring-opening reaction via asymmetrically coordinated Fe single atoms scaffolded by spoke-like mesoporous carbon nanospheres.

The ability to construct metal single-atom catalysts (SACs) asymmetrically coordinated with organic heteroatoms represents an important endeavor toward developing high-performance catalysts over symmetrically coordinated counterparts. Moreover, it is of key importance in creating supporting matrix with porous architecture for situating SACs as it greatly impacts the mass diffusion and transport of electrolyte. Herein, we report the crafting of Fe single atoms with asymmetrically coordinated nitrogen (N) and phosphorus (P) atoms scaffolded by rationally designed mesoporous carbon nanospheres (MCNs) with spoke-like nanochannels for boosting ring-opening reaction of epoxide to produce an array of pharmacologically important -amino alcohols.

Dual effects of zearalenone on aflatoxin B1-induced liver and mammary gland toxicity in pregnant and lactating rats.

Food and feed are frequently co-contaminated with aflatoxin B1 (AFB1) and zearalenone (ZEN). This study investigated the effects of ZEN on the AFB1-induced liver and mammary gland toxicity in pregnant and lactating rats. AFB1 and ZEN co-exposure inhibited the growth of rats and caused oxidative stress and inflammatory responses in the liver and mammary gland.

Six-Step Continuous Flow Synthesis of Diclofenac Sodium via Cascade Etherification/Smiles Rearrangement Strategy: Tackling the Issues of Batch Processing.

Invited for the cover of this issue are Dang Cheng, Fener Chen and co-workers at Fudan University. The image depicts six-step continuous-flow synthesis of diclofenac sodium from commercially available aniline and chloroacetic acid in a desktop microchemical plant. Read the full text of the article at 10.

Biocatalytic dynamic reductive kinetic resolution of aryl α-chloro β-keto esters: divergent, stereocontrolled synthesis of diltiazem, clentiazem, and siratiazem.

The first systematic study of ketoreductase (KRED)-catalyzed dynamic reductive kinetic resolution (DYRKR) on aryl α-chloro β-keto esters was performed, and 15 structurally diverse chiral -aryl α-chloro β-hydroxy esters were synthesized in 74-98% isolated yields, along with moderate-to-excellent diastereoselectivity (up to >99 : 1 dr) and good-to-excellent enantioselectivity (mostly >99% ee). LfSDR1-catalyzed complete reduction of 100 g L of substrate 6b at a ten-gram scale was achieved with a continuous fed-batch strategy, affording -(2,3)-1b, the key intermediate of diltiazem, in a record-breaking space-time yield of 96 g L d. An eight-step synthesis of diltiazem, clentiazem, and siratiazem was accomplished in 32-45% overall yields, featuring this versatile biocatalytic reduction reaction as well as an efficient, green chlorination reaction in flow.

Periostin Attenuates Cyclophosphamide-induced Bladder Injury by Promoting Urothelial Stem Cell Proliferation and Macrophage Polarization.

Interstitial cystitis (IC) is a bladder syndrome of unclear etiology with no generally accepted treatment. Growing evidence suggest that periostin (POSTN) is an important homeostatic component in the tissue repair and regeneration in adulthood, but its function in urinary bladder regeneration is still unknown. Here we investigate whether POSTN is involved in bladder tissue repair in a cyclophosphamide (CYP)-induced interstitial cystitis model.

Six-Step Continuous Flow Synthesis of Diclofenac Sodium via Cascade Etherification/Smiles Rearrangement Strategy: Tackling the Issues of Batch Processing.

Diclofenac sodium is a widely used nonsteroidal anti-inflammatory drug (NSAID) as over-the-counter (OTC) medication for the treatment of inflammatory diseases. Herein, the development of an intensified six-step continuous flow synthesis of diclofenac sodium from commercially available aniline and chloroacetic acid is described. A challenging and unprecedented etherification/Smiles rearrangement cascade of 2-chloro-N-phenylacetamide and 2,6-dichlorophenol into hydroxyacetyldiphenylamine operated with the precise control of reaction conditions in continuous flow was realized as the key step in this multistep synthetic chemistry.

Development of a Fully Continuous-Flow Approach Towards Asymmetric Total Synthesis of Tetrahydroprotoberberine Natural Alkaloids.

Continuous flow synthetic technologies had been widely applied in the total synthesis in the past few decades. Fully continuous flow synthesis is still extremely focused on multi-step synthesis of complex natural pharmaceutical molecules. Thus, the development of fully continuous flow total synthesis of natural products is in demand but challenging.

MicroRNA-494-3p Exacerbates Renal Epithelial Cell Dysfunction by Targeting SOCS6 under High Glucose Treatment.

Background: Diabetic nephropathy is a common complication of the kidneys induced by diabetes and is the main cause of end-stage renal disease. MicroRNA-494-3p was reported to be upregulated in renal tissues collected from db/db mice, but its specific role in diabetic nephropathy was still unclear. This study aimed to explore the effect of miR-494-3p on renal fibrosis using an in vitro cell model of diabetic nephropathy.