Risk factors for necrotizing enterocolitis in small-for-gestational-age infants: a matched case-control study.

Few studies have focused on the risk factors for necrotizing enterocolitis (NEC) in small for gestational age (SGA) infants. The aim of this study was to identify the risk factors for NEC in SGA newborns. This study included consecutive SGA neonates admitted to a tertiary hospital in Jiangxi Province, China from Jan 2008 to Dec 2022. Patients with NEC (Bell's stage ≥ II) were assigned to the NEC group. Gestational age- and birth weight-matched non-NEC infants born during the same period at the same hospital were assigned to the control group. The risk factors associated with NEC were analyzed with univariate and logistic regression models. During the study period, 2,912 SGA infants were enrolled, 150 (5.15%) of whom developed NEC. In total, 143 patients and 143 controls were included in the NEC and control groups, respectively. Logistic regression analysis revealed that sepsis (OR 2.399, 95% CI 1.271-4.527, P = 0.007) and anemia (OR 2.214, 95% CI 1.166-4.204, P = 0.015) might increase the incidence of NEC in SGA infants and that prophylactic administration of probiotics (OR 0.492, 95% CI 0.303-0.799, P = 0.004) was a protective factor against NEC. Therefore, sepsis, anemia and a lack of probiotic use are independent risk factors for NEC in SGA infants.

Effect of lymphocyte-to-monocyte ratio on survival in septic patients: an observational cohort study.

Introduction: The purpose of the present study was to evaluate the potential relationship of lymphocyte-to-monocyte ratio (LMR) with outcomes of septic patients at intensive care unit (ICU) admission. Material and methods: 3087 septic patients were included in the final cohort by using the Medical Information Mart for Intensive Care (MIMIC) database. We evaluated the association of different groups of LMRmax with 28-day survival and 1-year survival via Kaplan-Meier (K-M) analysis and Cox regression analysis. Subgroups analysis of LMRmax was performed to further explore the effect of LMRmax on survival. Results: According to the optimal cut-off value, the cohort was divided into low-LMRmax and high-LMRmax groups. The 28-day and 1-year survival rates were 47.9% and 19.9%, respectively, in the low-LMRmax group, and 60.4% and 25.9%, respectively, in the high-LMRmax group. Univariate logistic regression and K-M analyses revealed that the 28-day and 1-year survival rates of the high-LMRmax group were higher than those of the low-LMRmax group (both p < 0.001). A subgroup analysis of LMRmax identified a significant stepwise decrease in the risk of death at 28 days and 1 year from group 1 to group 4 (LMRmax increased gradually) after adjustment for multiple variables. Conclusions: We report for the first time that a lower LMRmax value is independently predictive of a poor prognosis in septic patients. Therefore, as an inexpensive and readily available indicator, LMRmax may facilitate stratification of prognosis in septic patients.

Research on detection method of photovoltaic cell surface dirt based on image processing technology.

In view of the reduced power generation efficiency caused by ash or dirt on the surface of photovoltaic panels, and the problems of heavy workload and low efficiency faced by manual detection, this study proposes a method to detect dust or dust on the surface of photovoltaic cells with the help of image processing technology to timely eliminate hidden dangers and improve power generation efficiency.This paper introduces image processing methods based on mathematical morphology, such as image enhancement, image sharpening, image filtering and image closing operation, which makes the image better highlight the target to be recognized. At the same time, it also solves the problem of uneven image binarization caused by uneven illumination in the process of image acquisition. By using the image histogram equalization, the gray level concentration area of the original image is opened or the gray level is evenly distributed, so that the dynamic range of the pixel gray level is increased, so that the image contrast or contrast is increased, the image details are clear, to achieve the purpose of enhancement. When identifying the target area, the method of calculating the proportion of the dirt area to the whole image area is adopted, and the ratio exceeding a certain threshold is judged as a fault. In addition, the improved A* path planning algorithm is adopted in this study, which greatly improves the efficiency of the unmanned aerial vehicle detection of photovoltaic cell dirt, saves time and resources, reduces operation and maintenance costs, and improves the operation and maintenance level of photovoltaic units.

Radical Deoxygenative Three-Component Reaction of Alcohols, Aryl Alkenes, and Cyanopyridines.

We report herein a deoxygenative radical multicomponent reaction involving alcohols, aryl alkenes, and cyanopyridine under photoredox conditions. This method is photoredox-neutral, suitable for late-stage modification, and compatible with a wide array of alcohols as alkyl radical sources, including primary, secondary, and tertiary alcohols. This reaction comprises a radical relay mechanism encompassing the Giese addition of aryl alkenes by alkyl radicals, followed by the decyanative pyridination of benzyl radicals.

Defense against Paramecium predation via long filament morphology favors the survival of Raphidiopsis raciborskii populations.

Raphidiopsis blooms are notorious for cyanotoxin formation and strong invasiveness, threatening the stability of aquatic ecosystems and human health. The protozoa Paramecium can potentially serve as an organism for controlling Raphidiopsis blooms owing to its grazing effect. However, the grazing ability of Paramecium is largely determined by the size of the prey, and the population of Raphidiopsis consists of filaments of varying lengths and sizes. The selective grazing behavior of Paramecium toward short-length or small-sized filaments in the Raphidiopsis population, as opposed to long filaments, remains unclear. Therefore, in this study, we co-cultured the predator Paramecium sp. with different initial abundances and the prey Raphidiopsis raciborskii to explore this knowledge gap. Our results suggested that: (1) the population of R. raciborskii declined under the selective grazing effect of Paramecium sp. on short filaments, whereas R. raciborskii with long filaments survived; (2) the growth of Paramecium sp. feeding on the same abundance of R. raciborskii was reduced at higher initial abundances, whereas its carrying capacity exhibited an opposite trend; (3) under ingestion by Paramecium sp., the morphology of R. raciborskii developed in the direction of becoming larger, and higher initial abundances of Paramecium sp. intensified this process; (4) increasing initial abundance of Paramecium sp. aggravated the decline of R. raciborskii photosynthetic activity. Therefore, the grazing effect of Paramecium sp. on R. raciborskii mainly affects filaments of short length or small size. Collectively, these results clarify the inter-species interaction between the protozoa Paramecium and filamentous cyanobacteria Raphidiopsis, including population dynamics and morphological and physiological changes in the predator and prey. Such insights into the interactions between Paramecium and R. raciborskii may have implications for the biological control of blooms caused by filamentous cyanobacteria.

Sesquiterpene lactones from Tithonia diversifolia with ferroptosis-inducing activities.

Eight previously undescribed sesquiterpene lactones (1-8), together with six known ones (9-14) were isolated from the aerial parts of Tithonia diversifolia (Hemsl.) A. Gray. The absolute configurations of these compounds were elucidated using HRMS, NMR spectroscopy, optical rotation measurements, X-ray crystallography, and ECD. Among them, sesquiterpene lactones 2-4 share a unique carbon skeleton with a rare C-3/C-4 ring-opened structure. Compounds 1 and 8 showed moderate inhibitory effects toward CT26 murine colon carcinoma cells by promoting lipid ROS production, highlighting their potential as ferroptosis inducers.

A thematic content analysis of the structure and effects of good doctor abilities in China.

BACKGROUND: The efforts to explore and build the structure of good doctor abilities are important because they help improve the quality of education for medical students and better standardize the working performance of doctors. However, at present, no worldwide standards for such a structure have been established. In this study, we endeavoured to map the structure of good doctor abilities and identify their effects. METHODS: With a focus on China, a thematic content analysis was adopted in this study to analyse the personal profiles of 50 widely recognized good doctors. NVivo11 software was used. RESULTS: The Structure and Effects of Good Doctor Abilities in China model was proposed, and interpretations were made based on AMO theory. Good doctor abilities fall within six categories: rigorous clinical thinking, skilled in diagnosis and therapy, clinical empathy, continuous learning and innovation, enhancing and sharing experiences, and communication and coordination. These abilities have positive impacts on doctors' work performances and social benefits by encouraging good behaviours, ultimately promoting the sustainable development of the hospitals where they serve. CONCLUSIONS: In this study, we established a model of the structure and effects of good-doctor abilities in China and interpreted its mechanism, innovation and theory diversification in "good-doctor" research. Moreover, this study has practical significance because it provides systematic and well-targeted criteria for improving the professionalism of doctors, promoting more good doctor behaviours, providing guidance for regulating doctors' conduct and providing a reference for medical education and working performance reviews worldwide.

Synthesis and Biological Activities of Scleropentaside D.

We report the first total synthesis of scleropentaside D, a unique C-glycosidic ellagitannin, from the ketal derivative of scleropentaside A employing site-selective O4-protection of C-acyl glycoside and copper-catalyzed oxidative coupling reaction of galloyl groups as the key steps. Our study confirms the proposed structure of this natural product, scleropentaside D, and demonstrates its effectiveness as an inhibitor of α-glycosidase.

Role of transient receptor potential channels in the regulation of vascular tone.

Vascular tone is a major element in the control of hemodynamics. Transient receptor potential (TRP) channels conducting monovalent and/or divalent cations (e.g. Na+ and Ca2+) are expressed in the vasculature. Accumulating evidence suggests that TRP channels participate in regulating vascular tone by regulating intracellular Ca2+ signaling in both vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). Aberrant expression/function of TRP channels in the vasculature is associated with vascular dysfunction in systemic/pulmonary hypertension and metabolic syndromes. This review intends to summarize our current knowledge of TRP-mediated regulation of vascular tone in both physiological and pathophysiological conditions and to discuss potential therapeutic approaches to tackle abnormal vascular tone due to TRP dysfunction.

The pan immune inflammatory value in relation to non-alcoholic fatty liver disease and hepatic fibrosis.

BACKGROUND: Inflammation played a critical role in non-alcoholic fatty liver disease (NAFLD). Here, we aimed to explore the relationship between inflammatory biomarkers and the prevalence of NAFLD and hepatic fibrosis in US participants. METHODS: Individuals with complete data from National Health and Nutrition Examination Survey (NHANES), 2017-2020 pre-pandemic cycle dataset were referred to this study. We identified NAFLD by vibration-controlled transient elastography (VCTE) on the basis of controlling attenuation parameter (CAP) ≥274dB/m. Liver fibrosis was confirmed by liver stiffness measurement (LSM) ≥8.2kPa. Multivariate logistic regression models were applied to estimate the correlations between inflammatory biomarkers and the prevalence of NAFLD and hepatic fibrosis based on sample weights. RESULTS: All together 5026 subjects were incorporated into the study cohort. Among these subjects, 2209 were classified as having NAFLD, and 8.35 % were diagnosed with hepatic fibrosis. Pan immune inflammatory value (PIV), instead of systemic immune inflammatory index (SII), was positively correlated with the rate of NAFLD or hepatic fibrosis. Subgroup analysis for NAFLD revealed that the positive relationships of the PIV existed in males (OR=1.52, 95 % CI: 1.01-2.28, p = 0.046) and participants below 60 years of age (OR=1.49, 95 % CI: 1.05-2.1, p = 0.028). Moreover, subgroup analysis for hepatic fibrosis revealed that the positive relationships of the PIV existed in females (OR=2.09, 95 % CI: 1.2-3.63, p = 0.014) and participants below 60 years of age (OR=1.74, 95 % CI: 1.09-2.77, p = 0.023). CONCLUSIONS: A higher PIV, but not SII, is associated with a higher likelihood of NAFLD and liver fibrosis, suggesting that the PIV is a more valuable inflammatory marker for assessing NAFLD and liver fibrosis in participants, especially for those who are below 60 years of age.

Podocyte OTUD5 alleviates diabetic kidney disease through deubiquitinating TAK1 and reducing podocyte inflammation and injury.

Recent studies have shown the crucial role of podocyte injury in the development of diabetic kidney disease (DKD). Deubiquitinating modification of proteins is widely involved in the occurrence and development of diseases. Here, we explore the role and regulating mechanism of a deubiquitinating enzyme, OTUD5, in podocyte injury and DKD. RNA-seq analysis indicates a significantly decreased expression of OTUD5 in HG/PA-stimulated podocytes. Podocyte-specific Otud5 knockout exacerbates podocyte injury and DKD in both type 1 and type 2 diabetic mice. Furthermore, AVV9-mediated OTUD5 overexpression in podocytes shows a therapeutic effect against DKD. Mass spectrometry and co-immunoprecipitation experiments reveal an inflammation-regulating protein, TAK1, as the substrate of OTUD5 in podocytes. Mechanistically, OTUD5 deubiquitinates K63-linked TAK1 at the K158 site through its active site C224, which subsequently prevents the phosphorylation of TAK1 and reduces downstream inflammatory responses in podocytes. Our findings show an OTUD5-TAK1 axis in podocyte inflammation and injury and highlight the potential of OTUD5 as a promising therapeutic target for DKD.

Bioinspired Mechanochromic Liquid Crystal Materials: from Fundamentals to Functionalities and Applications.

Inspired by intriguing color changeable ability of natural animals, the design and fabrication of artificial mechanochromic materials capable of changing colors upon stretching or pressing have attracted intense scientific interest. Liquid crystal (LC) is a self-organized soft matter with anisotropic molecular alignment. Due to the sensitivity to various external stimulations, LC has been considered as an emerging and appealing responsive building block to construct intelligent materials and advanced devices. Recently, mechanochromic LC materials have becoming a hot topic in multi fields from flexible artificial skins to visualized sensors and smart biomimetic devices. In this review, the recent progress of mechanochromic LCs is comprehensively summarized. Firstly, the mechanism and functionalities of mechanochromic LC is introduced, followed by preparation of various functional materials based on mechanochromic LCs. Then the applications of mechanochromic LCs are provided. Finally, the conclusion and outlooks of this field is given. This overview is hoped to provide inspiration in fabrication of advanced functional soft materials for scientists and engineers from multidisciplines including materials science, elastomers, chemistry and physical science. This article is protected by copyright. All rights reserved.

Ion channel Piezo1 activation aggravates the endothelial dysfunction under a high glucose environment.

BACKGROUND: Vasculopathy is the most common complication of diabetes. Endothelial cells located in the innermost layer of blood vessels are constantly affected by blood flow or vascular components; thus, their mechanosensitivity plays an important role in mediating vascular regulation. Endothelial damage, one of the main causes of hyperglycemic vascular complications, has been extensively studied. However, the role of mechanosensitive signaling in hyperglycemic endothelial damage remains unclear. METHODS: Vascular endothelial-specific Piezo1 knockout mice were generated to investigate the effects of Piezo1 on Streptozotocin-induced hyperglycemia and vascular endothelial injury. In vitro activation or knockdown of Piezo1 was performed to evaluate the effects on the proliferation, migration, and tubular function of human umbilical vein endothelial cells in high glucose. Reactive oxygen species production, mitochondrial membrane potential alternations, and oxidative stress-related products were used to assess the extent of oxidative stress damage caused by Piezo1 activation. RESULTS: Our study found that in VECreERT2;Piezo1flox/flox mice with Piezo1 conditional knockout in vascular endothelial cells, Piezo1 deficiency alleviated streptozotocin-induced hyperglycemia with reduced apoptosis and abscission of thoracic aortic endothelial cells, and decreased the inflammatory response of aortic tissue caused by high glucose. Moreover, the knockout of Piezo1 showed a thinner thoracic aortic wall, reduced tunica media damage, and increased endothelial nitric oxide synthase expression in transgenic mice, indicating the relief of endothelial damage caused by hyperglycemia. We also showed that Piezo1 activation aggravated oxidative stress injury and resulted in severe dysfunction through the Ca2+-induced CaMKII-Nrf2 axis in human umbilical vein endothelial cells. In Piezo1 conditional knockout mice, Piezo1 deficiency partially restored superoxide dismutase activity and reduced malondialdehyde content in the thoracic aorta. Mechanistically, Piezo1 deficiency decreased CaMKII phosphorylation and restored the expression of Nrf2 and its downstream molecules HO-1 and NQO1. CONCLUSION: In summary, our study revealed that Piezo1 is involved in high glucose-induced oxidative stress injury and aggravated endothelial dysfunction, which have great significance for alleviating endothelial damage caused by hyperglycemia.

Copper-Catalyzed Difunctionalization of Propargylic Carbonates through Tandem Nucleophilic Substitution/Boroprotonation.

Highly functionalized organic molecules are in high demand, but their preparation is challenging. Copper-catalyzed transformation of alkynyl- and allenyl-containing substrates has emerged as a powerful tool to achieve this objective. Herein, an efficient copper-catalyzed difunctionalization of propargylic carbonates through tandem nucleophilic substitution/boroprotonation has been developed, affording the formation of thiol-, selenium-, and boron-functionalized alkenes with high yield and stereoselectivity. Two distinct catalytic mechanisms involving a single reaction without any requirement of catalyst change were successfully demonstrated.

N-doped 3D carbon encapsulating nickel selenide nanoarchitecture with cation defect engineering: An ultrafast and long-life anode for sodium-ion batteries.

Transition metal chalcogenides (TMCs) hold great potential for sodium-ion batteries (SIBs) owing to their multielectron conversion reactions, yet face challenges of poor intrinsic conductivity, sluggish diffusion kinetics, severe phase transitions, and structural collapse during cycling. Herein, a self-templating strategy is proposed for the synthesis of a class of metal cobalt-doped NiSe nanoparticles confined within three-dimensional (3D) N-doped macroporous carbon matrix nanohybrids (Co-NiSe/NMC). The cation defect engineering within the developed Co-NiSe and 3D N-doped carbon plays a crucial role in enhancing intrinsic conductivity, reinforcing structural stability, and reducing the barrier to sodium ion diffusion, which are verified by a series of electrochemical kinetic analyses and density functional theory calculations. Significantly, such cation defect engineering not only reduces overpotential but also accelerates conversion reaction kinetics, ensuring both exceptional high-rate capability and extended durability. Consequently, the optimally engineered Co-NiSe/NMC demonstrates a remarkable rate performance, delivering 390 mAh g-1 at 10 A g-1. Moreover, it exhibits an unprecedented lifespan, maintaining a remarkable capacity of 403 mAh g-1 after 1400 cycles and 318 mAh g-1 after 4000 cycles, even at high rates of 1.0 and 2.0 A g-1, respectively. This work marks a substantial advancement in achieving both high performance and prolonged cycle life in sodium-ion batteries.

Adenosine kinase inhibits ß-cell proliferation by upregulating DNA methyltransferase 3A expression.

AIM: To investigate the effects of adenosine kinase (ADK), a key enzyme in determining intracellular adenosine levels, on ß cells, and their underlying mechanism. METHODS: Genetic animal models and transgenic immortalized cells were applied to study the effect of ADK on islet beta-cell proliferation and function. The beta-cell mass and response to glucose were measured in vivo using mice with beta-cell-specific ADK overexpression, and in vitro using ADK-overexpressed immortalized beta-cell. RESULTS: The expression of ADK in human islets at high abundance, especially in ß cells, was decreased during the process of ß-cell proliferation. Additionally, a transgenic mouse model (ADKtg/tg /Mip-Cre) was generated wherein the mouse Insulin1 gene promoter specifically overexpressed ADK in pancreatic ß cells. The ADKtg/tg /Mip-Cre model exhibited impaired glucose tolerance, decreased fasting plasma insulin, loss of ß-cell mass, and inhibited ß-cell proliferation. Proteomic analysis revealed that ADK overexpression inhibited the expression of several proteins that promote cell proliferation and insulin secretion. Upregulating ADK in the ß-cell line inhibited the expression of ß-cell related regulatory molecules, including FoxO1, Appl1, Pxn, Pdx-1, Creb and Slc16a3. Subsequent in vitro experiments indicated that the inhibition of ß-cell proliferation and the decreased expression of Pdx-1, Creb and Slc16a3 were rescued by DNA methyltransferase 3A (DNMT3A) knockdown in ß cells. CONCLUSION: In this study, we found that the overexpression of ADK decreased the expression of several genes that regulate ß cells, resulting in the inhibition of ß-cell proliferation and dysfunction by upregulating the expression of DNMT3A.

Deep genome skimming reveals the hybrid origin of Pseudosasa gracilis (Poaceae: Bambusoideae).

Pseudosasa gracilis (Poaceae: Bambusoideae) is a temperate woody bamboo species endemic to South-central China with a narrow distribution. Previous phylogenetic studies revealed an unexpected, isolated phylogenetic position of Ps. gracilis. Here we conducted phylogenomic analysis by sampling populations of Ps. gracilis and its sympatric species Ps. nanunica and Sinosasa polytricha reflecting different genomic signals, by deep genome skimming. Integrating molecular evidence from chloroplast genes and genome-wide SNPs, we deciphered the phylogenetic relationships of Ps. gracilis. Both plastid and nuclear data indicate that Ps. gracilis is more closely related to Sinosasa, which is discordant with the taxonomic treatment. To further explore this molecular-morphological conflict, we screened 411 "perfect-copy" syntenic genes to reconstruct phylogenies using both the concatenation and coalescent methods. We observed extensive discordance between gene trees and the putative species tree. A significant hybridization event was detected based on 411 genes from the D subgenome, showing Ps. gracilis was a hybrid descendant between Sinosasa longiligulata and Ps. nanunica, with 63.56% and 36.44% inheritance probabilities of each parent. Moreover, introgression events were detected in the C subgenome between Ps. gracilis and S. polytricha in the same distribution region. Our findings suggest that sympatric hybridization and introgression play a crucial role in the origin of Ps. gracilis. By providing an empirical example of bamboo of hybrid origin using comprehensive analyses based on genomic data from different inheritance systems and morphological characters, our study represents a step forward in understanding of reticulate evolution of bamboos.

Analysis of chloroplast genome characteristics and codon usage bias in 14 species of Annonaceae.

For the study of species evolution, chloroplast gene expression, and transformation, the chloroplast genome is an invaluable resource. Codon usage bias (CUB) analysis is a tool that is utilized to improve gene expression and investigate evolutionary connections in genetic transformation. In this study, we analysed chloroplast genome differences, codon usage patterns and the sources of variation on CUB in 14 Annonaceae species using bioinformatics tools. The study showed that there was a significant variation in both gene sizes and numbers between the 14 species, but conservation was still maintained. It's worth noting that there were noticeable differences in the IR/SC sector boundary and the types of SSRs among the 14 species. The mono-nucleotide repeat type was the most common, with A/T repeats being more prevalent than G/C repeats. Among the different types of repeats, forward and palindromic repeats were the most abundant, followed by reverse repeats, and complement repeats were relatively rare. Codon composition analysis revealed that all 14 species had a frequency of GC lower than 50%. Additionally, it was observed that the proteins in-coding sequences of chloroplast genes tend to end with A/T at the third codon position. Among these species, 21 codons exhibited bias (RSCU > 1), and there were 8 high-frequency (HF) codons and 5 optimal codons that were identical across the species. According to the ENC-plot and Neutrality plot analysis, natural selection had less impact on the CUB of A. muricate and A. reticulata. Based on the PR2-plot, it was evident that base G had a higher frequency than C, and T had a higher frequency A. The correspondence analysis (COA) revealed that codon usage patterns different in Annonaceae.

Surface wettability control and electron transport regulation in zerovalent iron for enhanced removal of emerging polystyrene microplastics-heavy metal contaminants.

Emerging microplastics-heavy metal (MPs-HM) contaminants in wastewaters pose an emerging health and environmental risk due to their persistence and increasing ecological risks (e.g., "Trojan horse" effect). Hence, removing MPs in solution and preventing secondary releases of HM has become a key challenge when tackling with MPs pollution. Leveraging the hydrophobic nature of MPs and the electron transfer efficiency from Fe0 to HM, we demonstrate an alkylated and sulfidated nanoscale zerovalent iron (AS-nZVI) featuring a delicate "core-shell-hydrophobic film" nanostructure. Exemplified by polystyrene (PS) MPs-Pb(II) removal, the three nanocomponents offer synergistic functions for the rapid separation of MPs, as well as the reduction and stabilization of Pb(II). The outmost hydrophobic film of AS-nZVI greatly improves the anticorrosion performance of nanoscale zerovalent iron and the enrichment abilities of hydrophobic MPs, achieving a maximum removal capacity of MPs to 2725.87 mgMPs·gFe-1. This MPs enrichment promotes the subsequent reductive removal of Pb(II) through the electron transfer from the iron core of AS-nZVI to Pb(II), a process further strengthened by the introduced sulfur. When considering the inevitable aging of MPs in wastewaters due to mechanical wear or microbial degradation, our study concurrently examines the efficiencies and behaviors of AS-nZVI in removing virgin-MPs-Pb(II) and aged-MPs-Pb(II). The batch results reveal that AS-nZVI has an exceptional ability to remove above 99.6 % Pb(II) for all reaction systems. Overall, this work marks a pioneering effort in highlighting the importance of MPs-toxin combinations in dealing with MPs contamination and in demonstrating the utility of nZVI techniques for MPs-contaminated water purification.

Dehydroxylative radical N-glycosylation of heterocycles with 1-hydroxycarbohydrates enabled by copper metallaphotoredox catalysis.

N-Glycosylated heterocycles play important roles in biological systems and drug development. The synthesis of these compounds heavily relies on ionic N-glycosylation, which is usually constrained by factors such as labile glycosyl donors, precious metal catalysts, and stringent conditions. Herein, we report a dehydroxylative radical method for synthesizing N-glycosides by leveraging copper metallaphotoredox catalysis, in which stable and readily available 1-hydroxy carbohydrates are activated for direct N-glycosylation. Our method employs inexpensive photo- and copper- catalysts and can tolerate some extent of water. The reaction exhibits a broad substrate scope, encompassing 76 examples, and demonstrates high stereoselectivity, favoring 1,2-trans selectivity for furanoses and α-selectivity for pyranoses. It also exhibits high site-selectivity for substrates containing multiple N-atoms. The synthetic utility is showcased through the late-stage functionalization of bioactive compounds and pharmaceuticals like Olaparib, Axitinib, and Metaxalone. Mechanistic studies prove the presence of glycosyl radicals and the importance of copper metallaphotoredox catalysis.