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An efficient copper-promoted divergent phosphination of alkynylsulfonium salts 1 with secondary diarylphosphines 2 that tolerates a wide range of functional groups under mild conditions is reported. The use of excess alkynyl dibenzothiophenium salts (1/2 > 1, mole ratio) enables the phosphination to deliver alkynyl monophosphine products via a C(sp)-P cross-coupling in good to high yields, while the use of excess secondary diarylphosphines (1/2 < 0.5, mole ratio) leads to a type of cis-ethenyl bisphosphine products via sequential stereoselective double phosphination.
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A palladium-catalyzed regio- and stereo-selective phosphination of cyclic biarylsulfonium salts (racemic) with HPAr3Ar4 for straightforward synthesis of atropoisomeric phosphines (P,S-ligands) bearing a stereogenic axis or both a stereogenic axis and a P-stereogenic center is reported. The high reactivity and regio- and stereo-selectivity originate from the torsional strain release and palladium catalysis, and the construction of a P-stereogenic center is enabled by an efficient dynamic kinetic resolution. The high performance of the nascent P,S-ligands has been demonstrated in palladium-catalyzed asymmetric allylic substitutions, indicating the great potential of the present methodology.
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AIM: To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy (DR) and provide a novel strategy to elucidate the pathological mechanism of DR. METHODS: The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy (PDR), 23 with non-proliferative retinopathy (NPDR), 27 without retinopathy (DM), and 29 from the sex-, age- and BMI- matched healthy controls (29 HC) were analyzed by 16S rDNA gene sequencing. Sixty fecal samples from PDR, DM, and HC groups were assayed by untargeted metabolomics. Fecal metabolites were measured using liquid chromatography-mass spectrometry (LC-MS) analysis. Associations between gut microbiota and fecal metabolites were analyzed. RESULTS: A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR, and the close correlation of the disease progression with PDR-related microbiome and metabolites were found. To be specific, the structure of gut microbiota differed in four groups. Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups, than those in DM and HC groups. A cluster of microbiome enriched in PDR group, including Pseudomonas, Ruminococcaceae-UCG-002, Ruminococcaceae-UCG-005, Christensenellaceae-R-7, was observed. Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group. Arginine, serine, ornithine, and arachidonic acid were significantly enriched in PDR group, while proline was enriched in HC group. Functional analysis illustrated that arginine biosynthesis, lysine degradation, histidine catabolism, central carbon catabolism in cancer, D-arginine and D-ornithine catabolism were elevated in PDR group. Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine, ornithine levels in fecal samples. CONCLUSION: This study elaborates the different microbiota structure in the gut from four groups. The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR. Amino acid and fatty acid catabolism is especially disordered in PDR group. This may help provide a novel diagnostic parameter for DR, especially PDR.
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The Muscovy duck (Cairina moschata) is a waterfowl indigenous to the neotropical regions of Central and South America. It has low demand for concentrated feed and strong adaptability to different rearing conditions. After introduced to China through Eurasian commercial trade, Muscovy ducks have a domestication history of around 300 years in the Fujian Province of China. In the 1990s, the commodity Muscovy duck breed "Crimo," cultivated in Europe, entered the Chinese market for consumption and breeding purposes. Due to the different selective breeding processes, Muscovy ducks have various populational traits and lack transparency of their genetic background. To remove this burden in the Muscovy duck breeding process, we analyzed genomic data from 8 populations totaling 83 individuals. We identify 11.24 million single nucleotide polymorphisms (SNPs) and categorized these individuals into the Fujian-bred and the Crimo populations according to phylogenetic analyses. We then delved deeper into their evolutionary relationships through assessing population structure, calculating fixation index (FST) values, and measuring genetic distances. Our exploration of runs of homozygosity (ROHs) and homozygous-by-descent (HBD) uncovered genomic regions enriched for genes implicated in fatty acid metabolism, development, and immunity pathways. Selective sweep analyses further indicated strong selective pressures exerted on genes including TECR, STAT2, and TRAF5. These findings provide insights into genetic variations of Muscovy ducks, thus offering valuable information regarding genetic diversity, population conservation, and genome associated with the breeding of Muscovy ducks.
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Patos , Variação Genética , Genoma , Genômica , Polimorfismo de Nucleotídeo Único , Animais , Patos/genética , Genômica/métodos , Filogenia , Genética Populacional , Seleção GenéticaRESUMO
Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease. Little is known about how gene expression and chromatin structure are regulated in NAFLD due to lack of suitable model. Ducks naturally develop fatty liver similar to serious human non-alcoholic fatty liver (NAFL) without adipose inflammation and liver fibrosis, thus serves as a good model for investigating molecular mechanisms of adipose metabolism and anti-inflammation. Here, we constructed a NAFLD model without adipose inflammation and liver fibrosis in ducks. By performing dynamic pathological and transcriptomic analyses, we identified critical genes involving in regulation of the NF-κB and MHCII signaling, which usually lead to adipose inflammation and liver fibrosis. We further generated dynamic three-dimensional chromatin maps during liver fatty formation and recovery. This showed that ducks enlarged hepatocyte cell nuclei to reduce inter-chromosomal interaction, decompress chromatin structure, and alter strength of intra-TAD and loop interactions during fatty liver formation. These changes partially contributed to the tight control the NF-κB and the MHCII signaling. Our analysis uncovers duck chromatin reorganization might be advantageous to maintain liver regenerative capacity and reduce adipose inflammation. These findings shed light on new strategies for NAFLD control.
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Cromatina , Patos , Hepatopatia Gordurosa não Alcoólica , Animais , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Cromatina/metabolismo , Cromatina/genética , NF-kappa B/metabolismo , Inflamação/genética , Inflamação/patologia , Inflamação/metabolismo , Tecido Adiposo/metabolismo , Genoma , Fígado/metabolismo , Fígado/patologia , Modelos Animais de Doenças , Transdução de Sinais , Hepatócitos/metabolismo , Hepatócitos/patologia , Regulação da Expressão GênicaRESUMO
Antimicrobial peptides (AMPs) are antibiotic candidates; however, their instability and protease susceptibility limit clinical applications. In this study, the polylactic acid-glycolic acid (PLGA)-polyvinyl alcohol (PVA) drug delivery system was screened by orthogonal design using the double emulsion-solvent evaporation method. NZ2114 nanoparticles (NZ2114-NPs) displayed favorable physicochemical properties with a particle size of 178.11 ± 5.23 nm, polydispersity index (PDI) of 0.108 ± 0.10, ζ potential of 4.78 ± 0.67 mV, actual drug-loading rate of 4.07 ± 0.37%, encapsulation rate of 81.46 ± 7.42% and cumulative release rate of 67.75% (120 h) in PBS. The results showed that PLGA encapsulation increased HaCaT cell viability by 20%, peptide retention in 50% serum by 24.12%, and trypsin tolerance by 4.24-fold. Meanwhile, in vitro antimicrobial assays showed that NZ2114-NPs had high inhibitory activity against Staphylococcus epidermidis (S. epidermidis) (4-8 µg/mL). Colony counting and confocal laser scanning microscopy (CLSM) confirmed that NZ2114-NPs were effective in reducing the biofilm thickness and bacterial population of S. epidermidis G4 with a 99% bactericidal rate of persister bacteria, which was significantly better than that of free NZ2114. In conclusion, the results demonstrated that PLGA nanoparticles can be used as a reliable NZ2114 delivery system for the treatment of biofilm infections caused by S. epidermidis.
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BACKGROUND: The duck (Anas platyrhynchos) is one of the principal natural hosts of influenza A virus (IAV), harbors almost all subtypes of IAVs and resists to many IAVs which cause extreme virulence in chicken and human. However, the response of duck's adaptive immune system to IAV infection is poorly characterized due to lack of a detailed gene map of the major histocompatibility complex (MHC). RESULTS: We herein reported a chromosome-scale Beijing duck assembly by integrating Nanopore, Bionano, and Hi-C data. This new reference genome SKLA1.0 covers 40 chromosomes, improves the contig N50 of the previous duck assembly with highest contiguity (ZJU1.0) of more than a 5.79-fold, surpasses the chicken and zebra finch references in sequence contiguity and contains a complete genomic map of the MHC. Our 3D MHC genomic map demonstrated that gene family arrangement in this region was primordial; however, families such as AnplMHCI, AnplMHCIIß, AnplDMB, NKRL (NK cell receptor-like genes) and BTN underwent gene expansion events making this area complex. These gene families are distributed in two TADs and genes sharing the same TAD may work in a co-regulated model. CONCLUSIONS: These observations supported the hypothesis that duck's adaptive immunity had been optimized with expanded and diversified key immune genes which might help duck to combat influenza virus. This work provided a high-quality Beijing duck genome for biological research and shed light on new strategies for AIV control.
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Patos , Genoma , Animais , Humanos , Patos/genética , Complexo Principal de Histocompatibilidade/genética , Cromossomos/genética , Família MultigênicaRESUMO
The interaction between migratory birds and domestic waterfowl facilitates viral co-infections, leading to viral reassortment and the emergence of novel viruses. In 2022, samples were collected from duck farms around Poyang Lake in Jiangxi Province, China, which is located within the East Asia-Australasia flyway. Three strains of H4N6 avian influenza virus (AIV) were isolated. Genetic and phylogenetic analyses showed that the isolated H4N6 avian influenza viruses (AIVs) belonged to new genotypes, G23 and G24. All isolated strains demonstrated dual receptor binding properties. Additionally, the isolated strains were able to replicate efficiently not only in avian cells but also in mammalian cells. Furthermore, the H4N6 AIV isolates could infect chickens, with viral replication detected in the lungs and extrapulmonary organs, and could transmit within chicken flocks through contact, with viral shedding detected only in oropharyngeal swabs from chickens in the contact group. Notably, the H4N6 AIV could infect mice without prior adaptation and replicate in the lungs with high viral titers, suggesting that it is a potential threat to humans. In conclusion, this study provides valuable insight into the characteristics of H4N6 strains currently circulating in China.
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Vírus da Influenza A , Influenza Aviária , Animais , Camundongos , Galinhas , China , Patos , Mamíferos , FilogeniaRESUMO
A highly diastereo- and enantioselective phosphinative cyclization of ketone-enamides with secondary diarylphosphines enabled by copper catalysis is reported, providing a range of chiral tertiary cyclohexylphosphines bearing three contiguous stereogenic centers in high yields. This asymmetric phosphination-aldol cyclization protocol can also be extended to desymmetrization of dione-enamides to create four contiguous stereogenic centers in a highly selective manner.
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A dithiolation of alkenyl sulfonium salts with arylthiols is described, affording a series of 1,2-dithioalkanes in high yields. This protocol features mild and catalyst-free conditions and involves the formation of two C-S bonds sequentially via the regioselective addition of an arylthiol to the unsaturated CâC bonds, followed by the attack of another arylthiol to form 1,2-dithioalkanes exclusively.
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Herein, a stereoselective copper-catalyzed decarboxylative silylation of readily available vinylethylene carbonates (VECs) with PhMe2Si-Bpin is reported, affording a wide range of tri- and tetrasubstituted allylsilanes in moderate to high yields with E-selectivity. This protocol was characterized by high stereoselectivity, broad substrate scope, operational simplicity, and mild reaction conditions, which were amenable to diverse derivatizations and gram-scale synthesis.
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Purpose: Diabetic retinopathy (DR) is a common complication of diabetes and has a high prevalence. Dysregulation of circadian rhythmicity is associated with the development of DR. This research aimed to investigate rhythmical transcriptome alterations in the retina of diabetic mice. Methods: C57BL/6J mice were used to establish a diabetes model by intraperitoneal injection of streptozotocin (STZ). After 12 weeks, retinas were collected continuously at 4-hour intervals over 1 day. Total RNA was extracted from normal and STZ-treated retinas and RNA sequencing was performed. Meta2d algorithm, Kyoto Encyclopedia of Genes, Phase Set Enrichment Analysis, and time-series cluster analysis were used to identify, analyze and annotate the composition, phase, and molecular functions of rhythmic transcripts in retinas. Results: The retina exhibited powerful transcriptome rhythmicity. STZ-induced diabetes markedly modified the transcriptome characteristics of the circadian transcriptome in the retina, including composition, phase, and amplitude. Moreover, the diabetic mice led to re-organized temporal and clustering enrichment pathways in space and time and affected core clock machinery. Conclusions: Diabetes impairs the circadian rhythm of the transcriptomic profile of retinas. This study offers new perspectives on the negative effects of diabetes on the retina, which may provide important information for the development of new treatments for DR.
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Diabetes Mellitus Experimental , Retinopatia Diabética , Camundongos , Animais , Transcriptoma , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Camundongos Endogâmicos C57BL , Retina/metabolismo , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Ritmo Circadiano/genéticaRESUMO
An unprecedented geminal olefinic dichalcogenation of alkenyl sulfonium salts with dichalcogenides ArYYAr (Y = S, Se, Te) is reported, providing various trisubstituted 1,1-dichalcogenalkenes [Ar1CH = C(YAr2)2] in a highly selective manner under mild and catalyst-free conditions. The key process involves the formation of two geminal olefinic C-Y bonds via sequential C-Y cross-coupling and C-H chalcogenation. A mechanistic rationale is further supported by control experiments and density functional theory calculations.
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BACKGROUND: Diabetic retinopathy (DR) development is associated with disturbances in the gut microbiota and related metabolites. Butyric acid is one of the short-chain fatty acids (SCFAs), which has been found to possess a potential antidiabetic effect. However, whether butyrate has a role in DR remains elusive. This study aimed to investigate the effect and mechanism of sodium butyrate supplementation on DR. METHODS: C57BL/6J mice were divided into three groups: Control group, diabetic group, and diabetic with butyrate supplementation group. Type 1 diabetic mouse model was induced by streptozotocin. Sodium butyrate was administered by gavage to the experimental group daily for 12 weeks. Optic coherence tomography, hematoxylin-eosin, and immunostaining of whole-mount retina were used to value the changes in retinal structure. Electroretinography was performed to assess the retinal visual function. The tight junction proteins in intestinal tissue were evaluated using immunohistochemistry. 16S rRNA sequencing and LC-MS/MS were performed to determine the alteration and correlation of the gut microbiota and systemic SCFAs. RESULTS: Butyrate decreased blood glucose, food, and water consumption. Meanwhile, it alleviated retinal thinning and activated microglial cells but improved electroretinography visual function. Additionally, butyrate effectively enhanced the expression of ZO-1 and Occludin proteins in the small intestine. Crucially, only butyric acid, 4-methylvaleric acid, and caproic acid were significantly decreased in the plasma of diabetic mice and improved after butyrate supplementation. The deeper correlation analysis revealed nine genera strongly positively or negatively correlated with the above three SCFAs. Of note, all three positively correlated genera, including norank_f_Muribaculaceae, Ileibacterium, and Dubosiella, were significantly decreased in the diabetic mice with or without butyrate treatment. Interestingly, among the six negatively correlated genera, Escherichia-Shigella and Enterococcus were increased, while Lactobacillus, Bifidobacterium, Lachnospiraceae_NK4A136_group, and unclassified_f_Lachnospiraceae were decreased after butyrate supplementation. CONCLUSION: Together, these findings demonstrate the microbiota regulating and diabetic therapeutic effects of butyrate, which can be used as a potential food supplement alternative to DR medicine.
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Diabetes Mellitus Experimental , Retinopatia Diabética , Microbioma Gastrointestinal , Animais , Camundongos , Ácido Butírico/farmacologia , Ácido Butírico/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , RNA Ribossômico 16S , Cromatografia Líquida , Camundongos Endogâmicos C57BL , Espectrometria de Massas em Tandem , Ácidos Graxos Voláteis/farmacologia , Ácidos Graxos Voláteis/uso terapêuticoRESUMO
The gut microbiome that inhabits human hosts plays an important role in the development of a healthy host immune system. Many studies have shown that gut microbiota is involved in the occurrence and development of diabetic retinopathy (DR). With the advent of sequencing technology of the bacterial 16S ribosomal RNA (rRNA) gene, microbiota studies are becoming more feasible. Here, we described a study protocol to characterize the microbiota composite in the DR and non-DR patients compared with healthy controls.
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Diabetes Mellitus , Retinopatia Diabética , Microbioma Gastrointestinal , Microbiota , Humanos , Microbioma Gastrointestinal/genética , Fezes/microbiologia , Microbiota/genética , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of most common diseases in the world. Recently, alternative splicing (AS) has been reported to play a key role in NAFLD processes in mammals. Ducks can quickly form fatty liver similar to human NAFLD after overfeeding and restore to normal liver in a short time, suggesting that ducks are an excellent model to unravel molecular mechanisms of lipid metabolism for NAFLD. However, how alternative splicing events (ASEs) affect the fatty liver process in ducks is still unclear. RESULTS: Here we identify 126,277 unique transcripts in liver tissue from an overfed duck (77,237 total transcripts) and its sibling control (69,618 total transcripts). We combined these full-length transcripts with Illumina RNA-seq data from five pairs of overfed ducks and control individuals. Full-length transcript sequencing provided us with structural information of transcripts and Illumina RNA-seq data reveals the expressional profile of each transcript. We found, among these unique transcripts, 30,618 were lncRNAs and 1,744 transcripts including 155 lncRNAs and 1,589 coding transcripts showed significantly differential expression in liver tissues between overfed ducks and control individuals. We also detected 27,317 ASEs and 142 of them showed significant relative abundance changes in ducks under different feeding conditions. Full-length transcript profiles together with Illumina RNA-seq data demonstrated that 10 genes involving in lipid metabolism had ASEs with significantly differential abundance in normally fed (control) and overfed ducks. Among these genes, protein products of five genes (CYP4F22, BTN, GSTA2, ADH5, and DHRS2 genes) were changed by ASEs. CONCLUSIONS: This study presents an example of how to identify ASEs related to important biological processes, such as fatty liver formation, using full-length transcripts alongside Illumina RNA-seq data. Based on these data, we screened out ASEs of lipid-metabolism related genes which might respond to overfeeding. Our future ability to explore the function of genes showing AS differences between overfed ducks and their sibling controls, using genetic manipulations and co-evolutionary studies, will certainly extend our knowledge of genes related to the non-pathogenic fatty liver process.
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Processamento Alternativo , Hepatopatia Gordurosa não Alcoólica , RNA Longo não Codificante , Animais , Patos , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/veterináriaRESUMO
A rhodium-catalyzed highly enantio- and diastereoselective alkenylation of ß,γ-unsaturated butenolides is reported. The use of a chiral diene ligand, (S,S)-Ph-bod, enables the facile synthesis of chiral butyrolactones in high yields with extremely high enantioselectivities (>99% ee in all cases) and high diastereoselectivities (up to >20:1 dr). The key process of the reaction involves the isomerization of ß,γ-unsaturated butenolides to racemic α,ß-unsaturated butenolides and the subsequent dynamic kinetic resolution through ligand-controlled, enantioselective alkenylation with an alkenylrhodium species that is generated in situ via 1,4-rhodium migration.
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INTRODUCTION: Although the dental age assessment is commonly applied in forensic and maturity evaluation, the long-standing dilemma from population differences has limited its application. OBJECTIVES: This study aimed to verify the efficacy of the machine learning (ML) to build up the dental age standard of a local population. METHODS: We retrospectively studied 2052 panoramic films retrieved from healthy Taiwanese children aged 2.6-17.7 years with comparable sizes in each age-group. The recently reported Han population-based standard (H method) served as the control condition. To develop and validate ML models, random divisions of the sample in an 80%-20% ratio repeated 20 times. The model performances were compared with the H method, Demirjian's method, and Willems's method. RESULTS: The ML-assisted models provided more accurate age prediction than those non-ML-assisted methods. The range of errors was effectively reduced to less than one per year in the ML models. Furthermore, the consistent agreements among the age groups from preschool to adolescence were reported for the first time. The Gaussian process regression was the best ML model; of the non-ML modalities, the H method was the most efficacious, followed by the Demirjian's method and Willems's methods. CONCLUSION: The ML-assisted dental age assessment is helpful to provide customized standards to a local population with more accurate estimations in preschool and adolescent age groups than do studied conventional methods. In addition, the earlier complete tooth developments were also observed in present study. To construct more reliable dental maturity models in the future, additional environment-related factors should be taken into account.