Connecting the dots: the role of fatigue in female infertility.

Fatigue, an increasingly acknowledged symptom in various chronic diseases, has garnered heightened attention, during the medical era of bio-psycho-social model. Its persistence not only significantly compromises an individual's quality of life but also correlates with chronic organ damage. Surprisingly, the intricate relationship between fatigue and female reproductive health, specifically infertility, remains largely unexplored. Our exploration into the existing body of evidence establishes a compelling link between fatigue with uterine and ovarian diseases, as well as conditions associated with infertility, such as rheumatism. This observation suggests a potentially pivotal role of fatigue in influencing overall female fertility. Furthermore, we propose a hypothetical mechanism elucidating the impact of fatigue on infertility from multiple perspectives, postulating that neuroendocrine, neurotransmitter, inflammatory immune, and mitochondrial dysfunction resulting from fatigue and its co-factors may further contribute to endocrine disorders, menstrual irregularities, and sexual dysfunction, ultimately leading to infertility. In addition to providing this comprehensive theoretical framework, we summarize anti-fatigue strategies and accentuate current knowledge gaps. By doing so, our aim is to offer novel insights, stimulate further research, and advance our understanding of the crucial interplay between fatigue and female reproductive health.

Cross-sectional and longitudinal evaluation of white matter microstructure damage and cognitive correlations by automated fibre quantification in relapsing-remitting multiple sclerosis patients.

The purpose of this study was to characterize whole-brain white matter (WM) fibre tracts by automated fibre quantification (AFQ), capture subtle changes cross-sectionally and longitudinally in relapsing-remitting multiple sclerosis (RRMS) patients and explore correlations between these changes and cognitive performance A total of 114 RRMS patients and 71 healthy controls (HCs) were enrolled and follow-up investigations were conducted on 46 RRMS patients. Fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (AD), and radial diffusivity (RD) at each node along the 20 WM fibre tracts identified by AFQ were investigated cross-sectionally and longitudinally in entire and pointwise manners. Partial correlation analyses were performed between the abnormal metrics and cognitive performance. At baseline, compared with HCs, patients with RRMS showed a widespread decrease in FA and increases in MD, AD, and RD among tracts. In the pointwise comparisons, more detailed abnormalities were localized to specific positions. At follow-up, although there was no significant difference in the entire WM fibre tract, there was a reduction in FA in the posterior portion of the right superior longitudinal fasciculus (R_SLF) and elevations in MD and AD in the anterior and posterior portions of the right arcuate fasciculus (R_AF) in the pointwise analysis. Furthermore, the altered metrics were widely correlated with cognitive performance in RRMS patients. RRMS patients exhibited widespread WM microstructure alterations at baseline and alterations in certain regions at follow-up, and the altered metrics were widely correlated with cognitive performance in RRMS patients, which will enhance our understanding of WM microstructure damage and its cognitive correlation in RRMS patients.

ADAMTSL2 is a potential prognostic biomarker and immunotherapeutic target for colorectal cancer: Bioinformatic analysis and experimental verification.

The ADAMTS Like 2 (ADAMTSL2) mutation has been identified to be associated with different human genetic diseases. The role of ADAMTSL2 is unclear in colorectal cancer (CRC). The study investigated the expression of ADAMTSL2 in both pan cancer and CRC, using data from The Cancer Genome Atlas (TCGA) database to assess its diagnostic value. The study examined the correlation between ADAMTSL2 expression levels and clinical characteristics, as well as prognosis in CRC. The study explored potential regulatory networks involving ADAMTSL2, including its association with immune infiltration, immune checkpoint genes, tumor mutational burden (TMB) / microsatellite instability (MSI), tumor stemness index (mRNAsi), and drug sensitivity in CRC. ADAMTSL2 expression was validated using GSE71187 and quantitative real-time PCR (qRT-PCR). ADAMTSL2 was aberrantly expressed in pan cancer and CRC. An increased level of ADAMTSL2 expression in patients with CRC was significantly associated with the pathologic N stage (p < 0.001), pathologic stage (p < 0.001), age (p < 0.001), histological type (p < 0.001), and neoplasm type (p = 0.001). The high expression of ADAMTSL2 in patients with CRC was found to be significantly associated with a poorer overall survival (OS) (HR: 1.67; 95% CI: 1.18-2.38; p = 0.004), progression-free survival (PFS) (HR: 1.55; 95% CI: 1.14-2.11; p = 0.005) and disease-specific survival (DSS) (HR: 1.83; 95% CI: 1.16-2.89; p = 0.010). The expression of ADAMTSL2 in patients with CRC (p = 0.009) was identified as an independent prognostic determinant. ADAMTSL2 was associated with extracellular matrix receptor (ECM-receptor) interaction, transforming growth factor ß (TGF-ß) signaling pathway, and more. ADAMTSL2 expression was correlated with immune infiltration, immune checkpoint genes, TMB / MSI and mRNAsi in CRC. ADAMTSL2 expression was significantly and negatively correlated with 1-BET-762, Trametinib, and WZ3105 in CRC. ADAMTSL2 was significantly upregulated in CRC cell lines. The high expression of ADAMTSL2 is significantly correlated with lower OS and immune infiltration of CRC. ADAMTSL2 may be a potential prognostic biomarker and immunotherapeutic target for CRC patients.

Association between air pollution and male sexual function: A nationwide observational study in China.

This study aimed to explore the associations between air pollution and male sexual function. A total of 5047 male subjects in China were included in this study. The average air pollution exposure (PM2.5, PM10, SO2, CO, NO2, and O3) for the preceding 1, 3, 6, and 12 months before the participants' response was assessed. Male sexual function was evaluated using the International Index of Erectile Function-5 (IIEF-5) and the Premature Ejaculation Diagnostic Tool (PEDT). Generalized linear models were utilized to explore the associations between air pollution and male sexual function. K-prototype algorithm was conducted to identify the association among specific populations. Significant adverse effects on the IIEF-5 score were observed with NO2 exposure during the preceding 1, 3, and 6 months (1 m: ß = -5.26E-05; 3 m: ß = -4.83E-05; 6 m: ß = -4.23E-05, P < 0.05). PM2.5 exposure during the preceding 12 months was found to significantly negatively affect the PEDT after adjusting for confounding variables. Our research indicated negative correlations between air pollutant exposures and male sexual function for the first time. Furthermore, these associations were more pronounced among specific participants who maintain a normal BMI, exhibit extroverted traits, and currently engage in smoking and alcohol consumption.

Radiomics models based on cortical damages for identification of multiple sclerosis with cognitive impairment.

BACKGROUND: Cognitive impairment (CI) is a common symptom in multiple sclerosis (MS) patients. Cortical damages can be closely associated with cognitive network dysfunction and clinically significant CI in MS. So, in this study, We aimed to develop a radiomics model to efficiently identify the MS patients with CI based on clinical data and cortical damages. METHODS: One hundred and eighteen patients with MS were divided into CI and normal cognitive (NC) cohorts (62/56) as defined by the Montreal Cognitive Assessment (MoCA). All participants were randomly divided into train and test sets with a ratio of 7:3. The radiomic features were selected by using the least absolute shrinkage and selection operator (LASSO) method. The discrimination models were built with the support vector machines (SVM) by the clinical data, radiomic features, and merge data, respectively. And the patients were further divided according to each cognitive domain including memory, visuospatial, language, attention and executive, and each domain model was applied by the most suitable classifier. RESULTS: A total of 2298 features were extracted, of which 36 were finally selected. The merge model showed the greatest performance with the area under the curve (AUC) of 0.86 (95 % confidence interval: 0.81-0.91), accuracy (ACC) of 0.78, sensitivity of 0.79 and specificity of 0.77 in test cohort. However, although the visuospatial domain model showed the highest AUC of 0.71 (95 % confidence interval: 0.61-0.81) among five domain models, other domain models did not meet satisfactory results with a relatively low AUC, ACC, sensitivity and specificity. CONCLUSIONS: The radiomics model based on clinical data and cortical damages had a great potential to identify the MS patients with CI for clinical cognitive assessment.

Genetic mechanisms of fertilization failure and early embryonic arrest: a comprehensive review.

BACKGROUND: Infertility and pregnancy loss are longstanding problems. Successful fertilization and high-quality embryos are prerequisites for an ongoing pregnancy. Studies have proven that every stage in the human reproductive process is regulated by multiple genes and any problem, at any step, may lead to fertilization failure (FF) or early embryonic arrest (EEA). Doctors can diagnose the pathogenic factors involved in FF and EEA by using genetic methods. With the progress in the development of new genetic technologies, such as single-cell RNA analysis and whole-exome sequencing, a new approach has opened up for us to directly study human germ cells and reproductive development. These findings will help us to identify the unique mechanism(s) that leads to FF and EEA in order to find potential treatments. OBJECTIVE AND RATIONALE: The goal of this review is to compile current genetic knowledge related to FF and EEA, clarifying the mechanisms involved and providing clues for clinical diagnosis and treatment. SEARCH METHODS: PubMed was used to search for relevant research articles and reviews, primarily focusing on English-language publications from January 1978 to June 2023. The search terms included fertilization failure, early embryonic arrest, genetic, epigenetic, whole-exome sequencing, DNA methylation, chromosome, non-coding RNA, and other related keywords. Additional studies were identified by searching reference lists. This review primarily focuses on research conducted in humans. However, it also incorporates relevant data from animal models when applicable. The results were presented descriptively, and individual study quality was not assessed. OUTCOMES: A total of 233 relevant articles were included in the final review, from 3925 records identified initially. The review provides an overview of genetic factors and mechanisms involved in the human reproductive process. The genetic mutations and other genetic mechanisms of FF and EEA were systematically reviewed, for example, globozoospermia, oocyte activation failure, maternal effect gene mutations, zygotic genome activation abnormalities, chromosome abnormalities, and epigenetic abnormalities. Additionally, the review summarizes progress in treatments for different gene defects, offering new insights for clinical diagnosis and treatment. WIDER IMPLICATIONS: The information provided in this review will facilitate the development of more accurate molecular screening tools for diagnosing infertility using genetic markers and networks in human reproductive development. The findings will also help guide clinical practice by identifying appropriate interventions based on specific gene mutations. For example, when an individual has obvious gene mutations related to FF, ICSI is recommended instead of IVF. However, in the case of genetic defects such as phospholipase C zeta1 (PLCZ1), actin-like7A (ACTL7A), actin-like 9 (ACTL9), and IQ motif-containing N (IQCN), ICSI may also fail to fertilize. We can consider artificial oocyte activation technology with ICSI to improve fertilization rate and reduce monetary and time costs. In the future, fertility is expected to be improved or restored by interfering with or supplementing the relevant genes.

Insm1 regulates mTEC development and immune tolerance.

The expression of self-antigens in medullary thymic epithelial cells (mTECs) is essential for the establishment of immune tolerance, but the regulatory network that controls the generation and maintenance of the multitude of cell populations expressing self-antigens is poorly understood. Here, we show that Insm1, a zinc finger protein with known functions in neuroendocrine and neuronal cells, is broadly coexpressed with an autoimmune regulator (Aire) in mTECs. Insm1 expression is undetectable in most mimetic cell populations derived from mTECs but persists in neuroendocrine mimetic cells. Mutation of Insm1 in mice downregulated Aire expression, dysregulated the gene expression program of mTECs, and altered mTEC subpopulations and the expression of tissue-restricted antigens. Consistent with these findings, loss of Insm1 resulted in autoimmune responses in multiple peripheral tissues. We found that Insm1 regulates gene expression in mTECs by binding to chromatin. Interestingly, the majority of the Insm1 binding sites are co-occupied by Aire and enriched in superenhancer regions. Together, our data demonstrate the important role of Insm1 in the regulation of the repertoire of self-antigens needed to establish immune tolerance.

Nontargeted metabolomics analysis of follicular fluid in patients with endometriosis provides a new direction for the study of oocyte quality.

Endometriosis is a common, estrogen-dependent chronic gynecological disease that endangers the reproductive system and systemic metabolism of patients. We aimed to investigate the differences in metabolic profiles in the follicular fluid between infertile patients with endometriosis and controls. A total of 25 infertile patients with endometriosis and 25 infertile controls who were similar in age, BMI, fertilization method and ovulation induction treatment were recruited in this study. Metabolomics analysis of follicular fluid was performed by two methods of high-performance liquid chromatography tandem mass spectrometry. There were 36 upregulated and 17 downregulated metabolites in the follicular fluid of patients in the endometriosis group. KEGG pathway analysis revealed that these metabolites were enriched in phenylalanine, tyrosine and tryptophan biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine metabolism and pyrimidine metabolism pathways. A biomarker panel consisting of 20 metabolites was constructed by random forest, with an accuracy of 0.946 and an AUC of 0.988. This study characterizes differences in follicular fluid metabolites and associated pathway profiles in infertile patients with endometriosis. These findings can provide a better comprehensive understanding of the disease and a new direction for the study of oocyte quality, as well as potential metabolic markers for the prognosis of endometriosis.

Metabonomic analysis of follicular fluid in patients with diminished ovarian reserve.

Background: Ovarian reserve is an important factor determining female reproductive potential. The number and quality of oocytes in patients with diminished ovarian reserve (DOR) are reduced, and even if in vitro fertilization-embryo transfer (IVF-ET) is used to assist their pregnancy, the clinical pregnancy rate and live birth rate are still low. Infertility caused by reduced ovarian reserve is still one of the most difficult clinical problems in the field of reproduction. Follicular fluid is the microenvironment for oocyte survival, and the metabolic characteristics of follicular fluid can be obtained by metabolomics technology. By analyzing the metabolic status of follicular fluid, we hope to find the metabolic factors that affect the quality of oocytes and find new diagnostic markers to provide clues for early detection and intervention of patients with DOR. Methods: In this research, 26 infertile women with DOR and 28 volunteers with normal ovarian reserve receiving IVF/ET were recruited, and their follicular fluid samples were collected for a nontargeted metabonomic study. The orthogonal partial least squares discriminant analysis model was used to understand the separation trend of the two groups, KEGG was used to analyze the possible metabolic pathways involved in differential metabolites, and the random forest algorithm was used to establish the diagnostic model. Results: 12 upregulated and 32 downregulated differential metabolites were detected by metabolic analysis, mainly including amino acids, indoles, nucleosides, organic acids, steroids, phospholipids, fatty acyls, and organic oxygen compounds. Through KEGG analysis, these metabolites were mainly involved in aminoacyl-tRNA biosynthesis, tryptophan metabolism, pantothenate and CoA biosynthesis, and purine metabolism. The AUC value of the diagnostic model based on the top 10 metabolites was 0.9936. Conclusion: The follicular fluid of patients with DOR shows unique metabolic characteristics. These data can provide us with rich biochemical information and a research basis for exploring the pathogenesis of DOR and predicting ovarian reserve function.

Microstructural alterations in different types of lesions and their perilesional white matter in relapsing-remitting multiple sclerosis based on diffusion kurtosis imaging.

BACKGROUND AND OBJECTIVES: In multiple sclerosis (MS), contrast enhancement lesions and chronic active lesions have been demonstrated to have different degrees of inflammation. Accordingly, they exist different degrees of tissue damage, one is short and acute, and another is slow and longstanding. This study aimed to explore whether diffusion parameters can differentiate different types of lesions, and investigate the microstructural damage between different types of MS lesions by using diffusion magnetic resonance imaging (dMRI) and its correlation with clinical biomarkers of disability and cognitive states. METHODS: We retrospectively identified 77 contrast enhancement lesions (CELs), 384 iron rim lesions (IRLs), 393 non-iron rim lesions (NIRLs), their corresponding perilesional white matter (PLWM), and 68 normal-appearing white matter (NAWM) from 68 relapsing-remitting MS (RRMS). Additionally, 44 white matter in healthy controls (WM in HCs) were also enrolled in this study. The DTI and DKI parameters were measured in the above white matter, including kurtosis fractional anisotropy (KFA), fractional anisotropy (FA), mean kurtosis (MK), and mean diffusivity (MD). All the patients were assessed with the Digital Span Test (DST), the Symbol Digit Modalities Test (SDMT), the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), and the Expanded Disability Status Scale (EDSS). RESULTS: The lowest KFA, FA, MK values and the highest MD values were found in CELs, followed by IRLs, NIRLs, NAWM, and WM in HCs. In KFA and FA values, there were significant differences between each type of lesion, as well as each type of PLWM (P < 0.05). The MK values of CELs and IRLs were significantly lower than NIRLs, but inversely for MD (P < 0.05). There were no differences between CELs and IRLs for MK (P = 1) and MD (P = 0.261). The results of MK and MD values in CELs-PLWM and IRLs-PLWM were similar to the CELs and IRLs. There were no significant differences between NAWM and WM in HCs in all the enrolled diffusion parameters (P >0.05) and the FA values between NIRLs-PLWM and NAWM or between NIRLs-PLWM and WM in HCs were no significant differences (P >0.05). The KFA and MD values in IRLs-PLWM (r =0.443, P =0.021; r =-0.518, P =0.006) were correlated with the DST scores and the KFA of CELs-PLWM (r =0.396, P =0.041) was correlated with SDMT scores. CONCLUSION: Our findings demonstrate that the KFA values have the potential to distinguish different types of MS white matter tissues. Furthermore, the diffusion parameters can reflect the microstructure abnormalities in different MS lesions and might help us better understand the pathological mechanism and lesion evolution.

Sulfur dioxide may predominate in the adverse effects of ambient air pollutants on semen quality among the general population in Hefei, China.

Previous studies have reported potential adverse effects of exposure to ambient air pollutants on semen quality in infertile men, but studies on the general population have been limited and inconsistent, and the pollutants that play a major role remain unclear. This study aimed to explore the potential association between exposure to six air pollutants (PM2.5, PM10, NO2, SO2, O3 and CO) during different sperm development periods and semen quality among the general population, and to explore the interaction between different air pollutant exposures. We included 1515 semen samples collected from the Human Sperm Bank. We improved individuals' exposure level estimation by combining inverse distance weighting (IDW) interpolation with satellite remote sensing data. Multivariate linear regression models, restricted cubic spline functions and double-pollutant models were used to assess the relationship between exposure to six air pollutants and sperm volume, concentration, total sperm number and sperm motility. A negative association was found between SO2 exposure and progressive motility and total motility during 0-90 lag days and 70-90 lag days, and SO2 exposure during 10-14 lag days adversely affected sperm concentration and total sperm number. Sensitive analyses for qualified sperm donors and the double-pollutant models obtained similar results. Additionally, there were nonlinear relationships between exposure to PM, NO2, O3, CO and a few semen parameters, with NO2 and O3 exposure above the threshold showing negative correlations with total motility and progressive motility, respectively. Our study suggested that SO2 may play a dominant role in the adverse effects of ambient air pollutants on semen quality in the general population by decreasing sperm motility, sperm concentration and total sperm number. Also, even SO2 exposure lower than the recommended standards of the World Health Organization (WHO) could still cause male reproductive toxicity, which deserves attention.

Defect-assisted, spray-printed colloidal quantum dot microlasers for biosensing.

This study successfully implements spectrally distinguishable CdSe-ZnS core-shell colloidal quantum dot (CQD) microlasers by a simple, efficient spray printing technique and demonstrates its potential in biosensing. We have systematically characterized the optical properties of printed microring lasers with diameters less than 60 µm. The smallest structure that can be excited has a diameter as small as 30 µm, which is much smaller than the counterparts prepared by piezoelectric ink-jet printing. The detection sensitivity of 4.54 nm/min/refractive index unit is verified in glucose sensing using a printed CQD microlaser. Biosensing of diverse glucose and bovine serum albumin solutions using printed microlasers with the assistance of defects demonstrates a new, to the best of our knowledge, prototype for the development of high-performance, low-cost on-chip microcavity sensors.

Alterations in White Matter Fiber Tracts Characterized by Automated Fiber-Tract Quantification and Their Correlations With Cognitive Impairment in Neuromyelitis Optica Spectrum Disorder Patients.

Objectives: To investigate whether patients with neuromyelitis optica spectrum disorder (NMOSD) have tract-specific alterations in the white matter (WM) and the correlations between the alterations and cognitive impairment. Materials and Methods: In total, 40 patients with NMOSD and 20 healthy controls (HCs) who underwent diffusion tensor imaging (DTI) scan and neuropsychological scale assessments were enrolled. Automated fiber-tract quantification (AFQ) was applied to identify and quantify 100 equally spaced nodes of 18 specific WM fiber tracts for each participant. Then the group comparisons in DTI metrics and correlations between different DTI metrics and neuropsychological scales were performed. Results: Regardless of the entire or pointwise level in WM fiber tracts, patients with NMOSD exhibited a decreased fractional anisotropy (FA) in the left inferior fronto-occipital fasciculus (L_IFOF) and widespread increased mean diffusion (MD), axial diffusivity (AD), and radial diffusivity (RD), especially for the thalamic radiation (TR), corticospinal tract (CST), IFOF, inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF) [p < 0.05, false discovery rate (FDR) correction], and the pointwise analyses performed more sensitive. Furthermore, the negative correlations among MD, AD, RD, and symbol digit modalities test (SDMT) scores in the left TR (L_TR) were found in NMOSD. Conclusion: Patients with NMOSD exhibited the specific nodes of WM fiber tract damage, which can enhance our understanding of WM microstructural abnormalities in NMOSD. In addition, the altered DTI metrics were correlated with cognitive impairment, which can be used as imaging markers for the early identification of NMOSD cognitive impairment.

Metabolic Reprogramming of Immune Cells at the Maternal-Fetal Interface and the Development of Techniques for Immunometabolism.

Immunity and metabolism are interdependent and coordinated, which are the core mechanisms for the body to maintain homeostasis. In tumor immunology research, immunometabolism has been a research hotspot and has achieved groundbreaking changes in recent years. However, in the field of maternal-fetal medicine, research on immunometabolism is still lagging. Reports directly investigating the roles of immunometabolism in the endometrial microenvironment and regulation of maternal-fetal immune tolerance are relatively few. This review highlights the leading techniques used to study immunometabolism and their development, the immune cells at the maternal-fetal interface and their metabolic features required for the implementation of their functions, explores the interaction between immunometabolism and pregnancy regulation based on little evidence and clues, and attempts to propose some new research directions and perspectives.

The SNAG Domain of Insm1 Regulates Pancreatic Endocrine Cell Differentiation and Represses ß- to δ-Cell Transdifferentiation.

The allocation and specification of pancreatic endocrine lineages are tightly regulated by transcription factors. Disturbances in differentiation of these lineages contribute to the development of various metabolic diseases, including diabetes. The insulinoma-associated protein 1 (Insm1), which encodes a protein containing one SNAG domain and five zinc fingers, plays essential roles in pancreatic endocrine cell differentiation and in mature ß-cell function. In the current study, we compared the differentiation of pancreatic endocrine cells between Insm1 null and Insm1 SNAG domain mutants (Insm1delSNAG) to explore the specific function of the SNAG domain of Insm1. We show that the δ-cell number is increased in Insm1delSNAG but not in Insm1 null mutants as compared with the control mice. We also show a less severe reduction of the ß-cell number in Insm1delSNAG as that in Insm1 null mutants. In addition, similar deficits are observed in α-, PP, and ε-cells in Insm1delSNAG and Insm1 null mutants. We further identified that the increased δ-cell number is due to ß- to δ-cell transdifferentiation. Mechanistically, the SNAG domain of Insm1 interacts with Lsd1, the demethylase of H3K4me1/2. Mutation in the SNAG domain of Insm1 results in impaired recruitment of Lsd1 and increased H3K4me1/2 levels at hematopoietically expressed homeobox (Hhex) loci that are bound by Insm1, thereby promoting the transcriptional activity of the δ-cell-specific gene Hhex Our study has identified a novel function of the SNAG domain of Insm1 in the regulation of pancreatic endocrine cell differentiation, particularly in the repression of ß- to δ-cell transdifferentiation.

Mild synthesis of disaccharidic 2,3-enopyranosyl cyanides and 2-C-2-deoxy pyranosyl cyanides with Hg(CN)(2)/HgBr(2)/TMSCN.

Lewis acid-catalyzed dimerization of mono- and disaccharidic per-O-acetylated glycals gave di- and tetrasaccharidic O-acetylated C-glycosides, respectively. 2,3-Enopyranosyl cyanides were obtained from per-O-acetylated glycals by a new, mild anomeric S(N)'-acetoxy displacement with Hg(CN)(2)/HgBr(2)/TMSCN. Per-O-acetylated 2-C-2-deoxy-pyranoses were converted into pyranosyl cyanides by the same reagent. An unprecedented acetic acid elimination from dimers with D-galacto- and L-fuco-configurations accompanied the S(N)-displacement under those conditions. A new set of (1)H NMR coupling constants for 2,3-enopyranosyl systems was used for configurational assignment of complicated tetrasaccharide mimics.