Upper airway morphology in adults with positional obstructive sleep apnea.

PURPOSE: To compare the anatomical balance and shape of the upper airway in the supine position between adults with positional obstructive sleep apnea (POSA) and adults with non-positional OSA (NPOSA). METHODS: Adults diagnosed with OSA (apnea-hypopnea index (AHI) > 10 events/h) were assessed for eligibility. POSA was defined as the supine AHI more than twice the AHI in non-supine positions; otherwise, patients were classified as NPOSA. Cone beam computed tomography (CBCT) imaging was performed for every participant while awake in the supine position. The anatomical balance was calculated as the ratio of the tongue size to the maxillomandibular enclosure size. The upper airway shape was calculated as the ratio of the anteroposterior dimension to the lateral dimension at the location of the minimal cross-sectional area of the upper airway (CSAmin-shape). RESULTS: Of 47 participants (28 males, median age [interquartile range] 56 [46 to 63] years, median AHI 27.8 [15.0 to 33.8]), 34 participants were classified as having POSA (72%). The POSA group tended to have a higher proportion of males and a lower AHI than the NPOSA group (P = 0.07 and 0.07, respectively). After controlling for both sex and AHI, the anatomical balance and CSAmin-shape were not significantly different between both groups (P = 0.18 and 0.73, respectively). CONCLUSION: Adults with POSA and adults with NPOSA have similar anatomical balance and shape of their upper airway in the supine position. TRIAL REGISTRATION: This study was registered with the Australian New Zealand Clinical Trials Registry (ANZCTR Trial ACTRN12611000409976).

Characteristics of Metastatic and Nonmetastatic Pulmonary Sclerosing Pneumocytomas: A Clinicopathological Study of 68 Cases and 15 Reported Metastatic Cases.

To characterize the clinicopathologic features of pulmonary sclerosing pneumocytoma (PSP) and compare these features between the tumors with and without metastasis, 68 cases of PSP (1/68 [1.47%] with metastasis) diagnosed from 2009-2022 in our hospital and 15 previously reported metastasizing cases were studied. There were 54 female patients and 14 male patients, with age ranging from 17 to 72 years and tumor size ranging from 0.1 to 5.5 cm (mean, 1.75 cm). In all, 85.4% of the cases presented with ≥2 patterns, including papillary, sclerotic, solid, and hemorrhagic. Thyroid transcription factor 1, epithelial membrane antigen, CKpan, and CK7 were expressed in surface cells in 100% of the cases and napsin A was expressed in 90% of the cases. Stromal cell expression of these markers occurred in 100%, 93.9%, 13.5%, 13.8%, and 0% of the cases, respectively. Of the 16 PSP cases with metastasis, 8 were female patients and 7 were male patients, with age ranging from 14 to 73 years. The tumor size ranged from 2.5 to 12 cm (mean, 4.85 cm). Forty-five of the cases were negative for BRAF V600E immunostaining and 6 were focally weak positive, in which fluorescent PCR tests showed no detectable mutations. There were significant differences in gender, age, and tumor size between PSP cases with and without metastasis. No BRAF V600E mutation was found in patients with PSP. AKT1 p.E17K mutations were detected in both the primary lung tumor and the lymph node metastatic tumor of our PSP case with lymph node metastasis. In conclusion, PSP is an uncommon pulmonary neoplasm with significant female predilection and has distinct morphologic and immunohistochemical characteristics. The BRAFV600E mutation was not detectable in patients with PSP and thus may not involve in its tumorigenesis. Most PSP tumors are benign, with a minority exhibiting potential for metastasis and malignant behavior.

Comparison of the upper airway morphology between Dutch and Chinese adults with obstructive sleep apnea.

PURPOSE: The pathogenesis of obstructive sleep apnea (OSA) is complex and may vary between different races. It has been suggested that the anatomical balance between skeletal tissues and soft tissues around the upper airway is a key pathophysiologic factor of OSA. Therefore, the aim of this study was to compare the anatomical balance of the upper airway between Dutch and Chinese patients with OSA based on cone beam computed tomography (CBCT) images. METHODS: This was a cross-sectional study performed in two centers and included Dutch and Chinese adults with OSA. CBCT scans in the supine position were obtained for both Dutch and Chinese OSA groups. The primary outcome variable was the anatomical balance of the upper airway, defined as the ratio of the tongue area and the maxillomandibular enclosure area. RESULTS: A total of 28 Dutch adults (mean age ± SD of 46.6 ± 14.1 years, body mass index [BMI] of 26.8 ± 3.5 kg/m2, and apnea-hypopnea index [AHI] of 15.7 ± 7.1 events/h) and 24 Chinese adults (age 41.0 ± 12.4 years, BMI 26.5 ± 3.3 kg/m2, and AHI 16.5 ± 7.8 events/h). There were no significant differences in AHI, age, BMI, and sex between the two groups (P = 0.14-0.76). The Dutch group had a significantly larger tongue area and tongue length compared to the Chinese group (P = 0.01 and P < 0.01). On the other hand, the Chinese group had a smaller maxilla length compared to the Dutch group (P < 0.01). However, the anatomical balance of the upper airway of both groups was not significantly different (P = 0.16). CONCLUSION: Within the limitations of this study, no significant difference was found in the anatomical balance of the upper airway between Dutch and Chinese patients with mild to moderate OSA. TRIAL REGISTRATION: The present study was registered at the ClinicalTrials.gov identifier NCT03463785.

Effects of mandibular advancement devices on upper airway dimensions in obstructive sleep apnea: responders versus non-responders.

STUDY OBJECTIVES: To compare the effects of mandibular advancement device (MAD) therapy on upper airway dimensions between responders and non-responders with mild to moderate obstructive sleep apnea (OSA). METHODS: Thirty-one participants (21 men and 10 women) with a mean ± SD apnea-hypopnea index (AHI) of 16.6 ± 6.7 events/h, and aged 48.5 ± 13.9 years, were included in this study. Polysomnographic recordings and cone beam computed tomography (CBCT) scans in supine position were performed for every participant at baseline and at 3-month follow-up with their MAD in situ. Responders were defined as having ≥ 50% reduction in baseline AHI with a residual AHI < 10 events/h. The primary outcome variable was the minimal cross-sectional area of the upper airway (CSAmin). RESULTS: No significant differences were found between responders (n = 15) and non-responders (n = 16) in age, gender distribution, body mass index, and neck circumference (P = 0.06-0.93), nor in AHI and CSAmin (P = 0.40 and 0.65, respectively) at baseline. The changes of the CSAmin with MAD in situ in the responder group were not significantly different compared to those in the non-responder group (P = 0.06). CONCLUSION: Within the limitations of this study, we conclude that the changes of the upper airway dimensions induced by MADs are not significantly different between responders and non-responders with mild to moderate OSA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02724865. https://clinicaltrials.gov/ct2/show/NCT02724865.

Comparisons of the effects of two types of titratable mandibular advancement devices on respiratory parameters and upper airway dimensions in patients with obstructive sleep apnea: a randomized controlled trial.

OBJECTIVES: To compare the effects of two types of titratable mandibular advancement devices (MADs), namely MAD-H (allowing limited vertical opening) and MAD-S (allowing free vertical opening), on respiratory parameters and upper airway dimensions in patients with mild to moderate obstructive sleep apnea (OSA). MATERIALS AND METHODS: Patients with mild to moderate OSA (5 ≤ apnea-hypopnea index (AHI) < 30 /h) were randomly assigned to two parallel MAD groups. All MADs were subjectively titrated according to a standardized protocol during a 3-month follow-up. Every patient underwent two polysomnographic recordings, and two cone beam computed tomography scans in supine position: one at baseline and another one after 3 months with the MAD in situ. The primary outcome variables were the AHI in supine position (AHI-supine) and the minimal cross-sectional area of the upper airway in supine position (CSAmin-supine). RESULTS: A total of 49 patients were recruited, and 31 patients (21 men and 10 women) with a mean (± SD) age of 48.5 (± 13.9) years and a mean AHI of 16.6 (± 6.7) /h completed the study. In the per-protocol analysis, there was no significant difference between MAD-H (n = 16) and MAD-S (n = 15) in their effects on AHI-supine (P = 0.14) and CSAmin-supine (P = 0.59). Similar results were found in the intention-to-treat analysis (P = 0.47 and 0.57, respectively). CONCLUSIONS: Within the limitations of this study, we conclude that there is no significant difference in the effects of an MAD allowing limited vertical opening and an MAD allowing free vertical opening on respiratory parameters and upper airway dimensions in patients with mild to moderate OSA. CLINICAL RELEVANCE: MADs allowing limited vertical opening and allowing free vertical opening have similar effects on respiratory parameters and upper airway dimensions in patients with mild to moderate OSA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02724865. https://clinicaltrials.gov/ct2/show/NCT02724865.

Effects of miniscrew-assisted orthodontic treatment with premolar extractions on upper airway dimensions in adult patients with Class II high-angle malocclusion.

INTRODUCTION: The primary aim of this study was to investigate the change in upper airway dimensions and in mandibular position after miniscrew-assisted treatment with premolar extractions in adult patients with Class II high-angle malocclusion. The secondary aim was to determine the correlation between changes in upper airway dimensions and changes in mandibular position in these patients. METHODS: Eighteen adult patients with Class II high-angle malocclusion (mean ± standard deviation age = 21.2 ± 2.9 years) were selected retrospectively. All patients underwent 4 premolar extractions, and 2 miniscrews were implanted in the maxilla to intrude molar height. Cone beam computed tomography images were taken pretreatment and posttreatment for every patient. The primary outcome variable for the upper airway was the minimal cross-sectional area of the upper airway (CSAmin), and the primary outcome variables for the mandible were mandibular rotation (Mp-SN angle), mandibular horizontal position (SNB angle), and mandibular vertical position (ANS-Me distance). RESULTS: The CSAmin significantly increased by 47.2 mm2 (t = -2.26, P = 0.04) after orthodontic treatment. The mandible significantly rotated counterclockwise by 0.9° (t = 2.20, P = 0.04) after treatment, which consisted of forward movement of 1.2° (t = -4.30, P = 0.00) and upward movement of 1.3 mm (Z = -1.98, P = 0.05). Furthermore, the change of the CSAmin showed a significant correlation with the change of the ANS-Me (P = 0.01). CONCLUSIONS: By using miniscrews to intrude maxillary molars, orthodontic premolar extraction treatment results in mandibular counterclockwise rotation, and upper airway dimensions increase in Class II high-angle young adult patients. The increase of the upper airway dimensions significantly correlates to the upward movement of the mandible.

Bioinformatics and expression analysis of histone modification genes in grapevine predict their involvement in seed development, powdery mildew resistance, and hormonal signaling.

BACKGROUND: Histone modification genes (HMs) play potential roles in plant growth and development via influencing gene expression and chromatin structure. However, limited information is available about HMs genes in grapes (Vitis vinifera L.). RESULTS: Here, we described detailed genome-wide identification of HMs gene families in grapevine. We identified 117 HMs genes in grapevine and classified these genes into 11 subfamilies based on conserved domains and phylogenetic relationships with Arabidopsis. We described the genes in terms of their chromosomal locations and exon-intron distribution. Further, we investigated the evolutionary history, gene ontology (GO) analysis, and syntenic relationships between grapes and Arabidopsis. According to results 21% HMs genes are the result of duplication (tandem and segmental) events and all the duplicated genes have negative mode of selection. GO analysis predicted the presence of HMs proteins in cytoplasm, nucleus, and intracellular organelles. According to seed development expression profiling, many HMs grapevine genes were differentially expressed in seeded and seedless cultivars, suggesting their roles in seed development. Moreover, we checked the response of HMs genes against powdery mildew infection at different time points. Results have suggested the involvement of some genes in disease resistance regulation mechanism. Furthermore, the expression profiles of HMs genes were analyzed in response to different plant hormones (Abscisic acid, Jasmonic acid, Salicylic acid, and Ethylene) at different time points. All of the genes showed differential expression against one or more hormones. CONCLUSION: VvHMs genes might have potential roles in grapevine including seed development, disease resistance, and hormonal signaling pathways. Our study provides first detailed genome-wide identification and expression profiling of HMs genes in grapevine.

RNA interference in the progress of gastric cancer.

Gastric cancer is one of common malignant tumors. The development of molecular biology and genetics prompts people to regulate tumor cell regulation from the gene level, and seeks method to the new tumor therapy. RNA interference (which is also called RNAi) is a technology of double stranded RNAexogenous or dsRNA into cells, therefore this thereby inhibits the expression function of corresponding target gene. This paper summarizes the development process and the mechanism of RNAi technology, outlines the progress of experimental gastric cancer of the current RNAi technology, which shows that this technology can directly or indirectly inhibit tumor, and reduce the drug resistance of tumor cells. With the gradual improvement of RNAi technology, it will become a new direction for gene therapy of gastric cancer.

Visible-light induced cross-electrophile coupling of imines and anhydrides to synthesize α-amino ketones.

α-Amino ketones are important motifs in synthetic and medicinal chemistry. Efficient methods to directly access these motifs from feasible precursors are, however, limited. Herein, a visible-light mediated reductive cross-electrophile coupling of readily available imines and anhydrides was developed. Under mild reaction conditions, the umpolung reactivity of diverse imines engaged with anhydrides gives a variety of α-amino ketones with good yields and a broad functional group compatibility. Primary mechanistic studies revealed that this transformation might proceed through a radical-radical cross coupling pathway dominantly.

Dendronization of chitosan to afford unprecedent thermoresponsiveness and tunable microconfinement.

Convenient chemical modification of biomacromolecules to create novel biocompatible functional materials satisfies the current requirements of sustainable chemistry. Dendronization of chitosan with dendritic oligoethylene glycols (OEGs) paves a strategy for the preparation of functional dendronized chitosans (DCSs) with unprecedent thermoresponsive behavior, which inherit biological features from polysaccharides and the topological features from dendritic OEGs. In addition, densely packed dendritic OEG chains around the backbone provide efficient cooperative interactions and form an intriguing confined microenvironment based on the degradable biopolymers. In this perspective, we describe the principle for the preparation of the thermoresponsive DCSs, and focus on the molecular envelop effect from the hydrophobic microconfinement to the encapsulated guest molecules or moieties. Particular attention is put on their capacity to regulate behavior and the functions of the encapsulated guests through thermally-mediated dehydration and collapse of the densely packed dendritic OEGs. We believe that the methodology described here may provide prospects for the fabrication of functional materials from biomacromolecules, especially when used as environmentally friendly nanomaterials or in accurate diagnosis and therapy.

Novel practical stereoselective synthesis of a bicyclic hydantoino-thiolactone as the key intermediate for production of (+)-biotin.

Bicyclic hydantoinothiolactone (1), as the key intermediate for production of (+)-biotin, has been efficiently and high-stereoselectively synthesized from the cheap starting material l-cystine via nine steps in 44% overall yield. In this new practical synthesis, there are two characteristic steps worthy of note. One step is TMSOTf-catalyzed efficient cyanation of (3S,7aR)-6-benzyl-5-oxo-3-phenyltetrahydro-1H,3H-imidazo[1,5-c]thiazol-7-yl acetate, the other step is DBU-catalyzed rapid isomerization of trans-isomer to cis-isomer of the bicyclic hydantoinothiolactone.

Case report: The stroma-rich variant of Castleman's disease of hyaline-vascular type with atypical stromal cell proliferation and malignant potential: An exceptional rare case occurred in mediastinal lymph node.

The stroma-rich variant of Castleman disease of hyaline-vascular type (SR-HVCD) is characterized by interfollicular proliferation of the fibroblastic, myofibroblastic, and/or histiocytic-derived stromal cells, occurred in a background of Castleman disease of hyaline-vascular type (HVCD). It has been considered as a hyperplastic disorder by far. Herein, we presented a case of a 40-year-old male suffering from an occupation in the right middle mediastinum. Microscopically, the lesion was characterized by atretic lymphoid follicles and overgrowth of the interfollicular spindle-shaped cells. Those spindle cells were histologically bland in some areas, while exhibited notable cellular atypia and focal necrosis in other areas. SMA and CD68 were immunostained with a subset of the spindle cells in both areas, whereas p53 staining was only perceived in areas with markedly cellular atypia. In addition, indolent T-lymphoblastic proliferation (iT-LBP) was present inside the lesion. The patient developed multiple sites metastases 4 months after surgery, and succumbed to the disease at 7 months. Our case demonstrates for the first time that SR-HVCD have a tumorigenesis potential rather than a simple hyperplastic process. Such disorder should be carefully evaluated to avoid underdiagnosis.

The Influences of Soil and Meteorological Factors on the Growth and Fruit Quality of Chinese Jujube (Ziziphus jujuba Mill.).

Chinese jujube (Ziziphus jujuba Mill.) is attracting more and more attention worldwide due to their tasty and nutritious fruit with extremely high contents of vitamin C (Vc) and soluble sugar. In order to find out the main factors that influence jujube growth and reproductive adaptability, the phenological periods, vegetative growths, fruiting abilities, and fruit qualities of eight newly released cultivars were compared and comprehensively analyzed in three representative ecological sites of the three main jujube-producing regions including Fuping (Hebei), Taigu (Shanxi), and Alar (Xinjiang) in China. Our results showed that the characteristics of jujube cultivars were significantly affected by soil and meteorological factors. The fruit number per bearing shoot was much more affected by temperature, light, and rainfall. The fruit number per bearing shoot, contents of soluble solids, and soluble sugar and Vc contents in fruits were influenced more by meteorological factors. The content of flavonoids was affected by both soil and meteorological factors. A principal component analysis (PCA) indicated that cultivars suitable for planting in Fuping (Hebei) were Yuhong and Lengbaiyu. Zaocuimi, Fucuimi, and Zaoqiuhong were suitable to be cultivated in Taigu (Shanxi), while Zaocuimi, Yuhong, Yulu, Luzao 2, and Yueguang behaved better in Alar (Xinjiang). This study provides insights of the environmental factors on jujube yield and quality and therefore provides references for highly efficient jujube cultivation.

The characteristic of Yatu morphogenesis and the efficacy of exogenous hormones on the development of Yatu during fruit development in 'Yali' pear (Pyrus bretschneideri Rehd.).

Yatu is a protuberance formed on the base part of 'Yali' pear fruit, near the pedicel, causing a shape like a duck head termed Yatu. It is a typical phenotypic trait to evaluate fruit appearance quality. The mechanism for Yatu formation has not been clear yet. Here, 90.8% of fruits with Yatu generated in outer base part of fruits. Primitive cells of Yatu were found at 10 days after pollination (DAP). There were higher expression levels of PbGA20ox2, PbIPT7a, and PbIPT5a, lower transcription levels of PbGA2ox1, PbNCED1, and PbNCED3 in outer base part of fruits at 10 DAP, accompanied with significantly higher levels of GA3, ZR, (GA3+ ZR)/ABA, and lower ABA content compared to that in the inner base part of fruits. GA3 + 6-BA promoted Yatu development by increasing GA3 content at 10 and 20 DAP, and ZR content at 20 DAP. PAC suppressed Yatu morphogenesis and development by increasing ABA level at 10 DAP. These results suggest that Yatu usually generated in outer base part of fruits, relatively higher GA3 and ZR contents, lower ABA content promoted Yatu morphogenesis and development.

Effects of mesotrione on the control efficiency and chlorophyll fluorescence parameters of Chenopodium album under simulated rainfall conditions.

This experiment was conducted to study the effects of mesotrione on the control efficiency and chlorophyll fluorescence parameters of Chenopodium album. Simulating three rainfall intensities of 2 mm/h (light rain), 6 mm/h (moderate rain) and 10 mm/h (heavy rain) at different interval times (0.5 h, 1 h, 2 h, 4 h) to analyze variable regulation of the control effect, the photosynthetic pigment content and chlorophyll fluorescence parameters of C. album after spraying mesotrione. With the extension of rainfall time interval, the inhibition rate of plant height, plant control effect and fresh weight control effect of C. album were gradually increased, the inhibition effect of rainfall on the efficacy was gradually decreased, at the same time, the contents of chlorophyll a, chlorophyll b, carotenoids, the maximum photochemical quantum efficiency (Fv/Fm), the actual photochemical quantum yield (Y (II)) and quantum yield (Y (NO)) production of regular energy consumption of C. album were also increased, while the nonregulatory energy decreased gradually. The results showed that the contents of chlorophyll a and chlorophyll b in leaves of C. album increased significantly by 35.63% and 35.38% compared with the control under the condition of simulating 6 mm/h in interval 1 hour. The study suggested that simulating 10 mm/h rainfall intensity had the greatest effect on C. album, the photosynthetic pigment content, Fv/Fm and Y (II) of leaves were significantly higher than those in the control groups under 0.5 h, 1 h and 2 h interval treatments. The carotenoid content was the lowest and Y (NO) was the largest under the 4 h interval treatment. As is displayed that rainfall reduced the weed control effect in the aspect of controlling C. album on mesotrione, which is partly contributed to increase photosynthetic pigment content and enhance the PS II photochemical activity. In conclusion, the rain intensity of ≤2 mm/h did not affect the control effect of mesotrione on C. album. At 6 mm/h within 1 h after treatment, the control effect of fresh weight was significantly reduced by more than 7.14%, and at 10 mm/h within 2 h, the control effect was significantly reduced by more than 14.78%.

Systematic genome-wide and expression analysis of RNA-directed DNA methylation pathway genes in grapes predicts their involvement in multiple biological processes.

RNA-directed DNA methylation (RdDM) is an important epigenetic pathway in plants and mediates transcriptional silencing by siRNAs. Different gene families have role in the regulation of the RdDM pathway and there is a lack of information about these gene families in the grapes (Vitis vinifera L.). Here, we mentioned the genome-wide identification, bioinformatics analysis, evolutionary history, and expression profiling of VvRdDM pathway genes against various stresses, hormonal treatments as well as in different organs. Sixty VvRdDM genes belonging to fourteen different families were identified. All the genes were unevenly distributed and chromosome 4 contained the highest number of genes (7). Most of the genes showed similar exon-intron and motif distribution patterns within the same subfamilies. Out of 14 families, only members of 4 families underwent duplication events during the evolutionary process and 50% of members of the AGO family are the result of duplication events. Based on Ka/Ks ratio all duplicated gene pairs have a negative mode of selection. VvRdDM pathway genes showed differential spatiotemporal expression patterns against different hormone and stress treatments. Further, with multiple transcriptome analysis, some VvRdDM genes showed a broad spectrum of high expression in different organs at various stages, and VvRdDM genes also displayed different expression in seeded and seedless cultivars during different phases of seed development. This proposed that VvRdDM genes may play multiple roles in grape growth and development, especially in seed development. qRT-PCR analysis of selected genes further verified the critical roles of RdDM genes in multiple biological processes, especially in seed development/ovule abortion i.e., VvIDN2a, VvDRD1a, VvRDR1a, and VvRDR6. Our study provides detailed information about VvRdDM genes in perspective of gene structure and evolution, as well as expression pattern against different stress, hormones and in different plants parts. It provides new candidate gene resources for further functional characterization and molecular breeding of grapes.

Diagnostic significance of CyclinD1 and D2-40 expression for follicular neoplasm of the thyroid.

OBJECTIVES: To evaluate the expression and differential diagnostic significance of CyclinD1 and D2-40 in follicular neoplasm (FN) and other thyroid adenomatoid lesions. METHODS: A total of 144 cases of thyroid adenomatoid lesions were enrolled. Immunohistochemistry for CyclinD1 and D2-40 was performed. RESULTS: We found two patterns of CyclinD1 expression: nuclear (N) and cytoplasmic (C). The expression of N-CyclinD1 / C-CyclinD1 in FN (77.4%, 48/62; 50.0%, 31/62) was much higher than that in multinodular goiters with dominant nodules (MNG-DN) (16.4%, 10/61; 4.9%, 3/61) (p < 0.05). In contrast, the expression of D2-40 in MNG-DN (82.0%,50/61) was much higher than that in FN (4.8%, 3/62) (p < 0.05). In addition, unique staining patterns were observed: CyclinD1 showed no immunostaining only in all 8 cases of oncocytic cell tumors (OCT); D2-40 staining showed the characteristic wide distribution of lymphatic vessels in all 8 cases of poorly differentiated thyroid carcinoma (PDTC). Finally, the expression of CyclinD1 and D2-40 did not differ among follicular thyroid adenoma and follicular thyroid carcinoma / noninvasive follicular thyroid neoplasm with papillary-like nuclear features (p > 0.05). CONCLUSIONS: CyclinD1 and D2-40 are helpful diagnostic markers of FN, which can assist to discern FN from MNG-DN / OCT / PDTC.

Epimeric monosaccharide-quinone hybrids on gold electrodes toward the electrochemical probing of specific carbohydrate-protein recognitions.

Carbohydrates represent one of the most significant natural building blocks, which govern numerous critical biological and pathological processes through specific carbohydrate-receptor interactions on the cell surface. We present here a new class of electrochemical probes based on gold surface-coated epimeric monosaccharide-quinone hybrids toward the ingenious detection of specific epimeric carbohydrate-protein interactions. Glucose and galactose, which represent a pair of natural monosaccharide C4 epimers, were used to closely and solidly conjugate with the 1,4-dimethoxybenzene moiety via a single C-C glycosidic bond, followed by the introduction of a sulfhydryl anchor. The functionalized aryl C-glycosides were sequentially coated on the gold electrode via the self-assembled monolayer (SAM) technique. X-ray photoelectron spectroscopy (XPS) was used to confirm the SAM formation, by which different binding energies (BE) between the glucosyl and the galactosyl SAMs on the surface, probably rendered by their epimeric identity, were observed. The subsequent electrochemical deprotection process readily furnished the surface-confined quinone/hydroquinone redox couple, leading to the formation of electrochemically active epimeric monosaccharide-quinone SAMs on the gold electrode. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) used for the detection of specific sugar-lectin interactions indicated that the addition of specific lectin to the corresponding monosaccharide-quinone surface, i.e., concanavalin A (Con A) to the glucosyl SAM and peanut agglutinin (PNA) to the galactosyl SAM, resulted in an obvious decrease in peak current, whereas the addition of nonspecific lectins to the same SAMs gave very minor current variations. Such data suggested our uniquely constructed gold surface coated by sugar-quinone hybrids to be applicable as electrochemical probes for the detection of specific sugar-protein interactions, presumably leading to a new electrochemistry platform toward the study of carbohydrate-mediated intercellular recognitions.

Discovering the distinct inhibitory effects between C4-epimeric glycosyl amino acids: new insight into the development of protein tyrosine phosphatase inhibitors.

There has been increasing interest in the development of drug candidates based on sugar templates that possess rich structural and, especially, configurational diversities. We disclose herein that the epimeric identity between methyl 3,4-bis-phenylalanyl/tyrosinyl triazolyl-alpha-D-galactopyranoside and glucopyranoside may lead to their distinct inhibitory effects on specific protein tyrosine phosphatases (PTPs). Subsequently performed molecular docking study elucidated the plausible binding behaviors of the more potent galactosyl inhibitors with their primary PTP target, i.e. Cell Division Cycle 25B (CDC25B) phosphatase.

A unique and rapid approach toward the efficient development of novel protein tyrosine phosphatase (PTP) inhibitors based on 'clicked' pseudo-glycopeptides.

There has been considerable interest in the development of protein tyrosine phosphatase (PTP) inhibitors since many of the PTP members are tightly associated with major human diseases including autoimmune disorders, diabetes and cancer. We report here a unique and rapid approach toward the development of novel PTP inhibitor entities based on triazolyl pseudo-glycopeptides. By employing microwave-accelerated Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC or 'click reaction'), a series of triazole-linked serinyl, threoninyl, phenylalaninyl and tyrosinyl 1-O-gluco- or galactosides have been efficiently synthesized in high yields within only ~30 min. Successive biological assay identified these glycopeptidotriazoles as favorable PTP1B and CDC25B inhibitors with selectivity over TCPTP, LAR, SHP-1 and SHP-2. Both the structural diversity of the amino acid (Ser, Thr, Phe and Tyr) introduced and the epimeric identity (Glc or Gal) on monosaccharide scaffold were determined to impact the corresponding inhibitory activity and selectivity. In addition, the benzylated sugar scaffold was demonstrated to act as a crucial role for enhancing the binding affinity of the inhibitors with the targeted PTP. Docking simulation was eventually conducted to propose plausible binding modes of this compound series with PTP1B and CDC25B. Our approach readily realized from naturally abundant raw materials (sugar and amino acid) and via facile, regioselective and expeditious synthetic method (microwave-assisted click reaction) might provide new insights toward the 'click' fabrication of structurally diverse PTP inhibitors.