Carbohydrates are diverse bio-macromolecules with highly complex structures that are involved in numerous biological processes. Well-defined carbohydrates obtained by chemical synthesis are essential ...to the understanding of their functions. However, synthesis of carbohydrates is greatly hampered by its insufficient efficiency. So far, assembly of long carbohydrate chains remains one of the most challenging tasks for synthetic chemists. Here we describe a highly efficient assembly of a 92-mer polysaccharide by the preactivation-based one-pot glycosylation protocol. Several linear and branched oligosaccharide/polysaccharide fragments ranging from 5-mer to 31-mer in length have been rapidly constructed in one-pot manner, which enables the first total synthesis of a biologically important mycobacterial arabinogalactan through a highly convergent 31+31+30 coupling reaction. Our results show that the preactivation-based one-pot glycosylation protocol may provide access to the construction of long and complicated carbohydrate chains.
In this study, we report the design and fabrication of a novel biocompatible sponge with excellent antibacterial property, making it a promising material for wound dressings. The sponge is formed by ...grafting amoxicillin onto regenerated bacterial cellulose (RBC). It was observed that the grafted RBC could enhance the antibacterial activity against fungus, Gram-negative, and Gram-positive bacteria. The morphology of strains treated with the grafted RBC and fluorescent stain results further demonstrated the antibacterial ability of the fabricated sponge. Moreover, a cytocompatibility test evaluated in vitro and in vivo illustrates the nontoxicity of the prepared sponge. More importantly, the wound infection model reveals that this sponge can accelerate the wound healing in vivo. This work indicates the novel sponge has the huge potential in wound dressing application for clinical use.
Weight loss is common in patients with Amyotrophic lateral sclerosis (ALS), and associated with disease progression. Loss of appetite has been shown to be a contributor to weight loss in patients ...with amyotrophic lateral sclerosis (ALS). However, the reason of loss of appetite is not clear. The Council on Nutrition appetite questionnaire (CNAQ) and the simplified nutritional appetite questionnaire (SNAQ) are short and simple appetite assessment tools, which were using in ALS patients. In our study, the CNAQ and SNAQ were translated into Chinese, and their reliability and validity were tested. The Chinese version of the CNAQ (CNAQ-C) presented more appropriate reliability and validity than the SNAQ. Among the 94 ALS patients, 50 patients (53.2%) had loss of appetite, and we found that anxiety and/or depression contributed to the loss of appetite in the ALS patients. We reconfirmed that loss of appetite was associated with greater weight loss but not with clinical features of ALS. The loss of appetite caused by emotional problems in ALS patients should be taken seriously, and early intervention should be implemented to reduce weight loss.
New gene origination is a major source of genomic innovations that confer phenotyp ic changes and biological di- versity. Generation of new mitochondrial genes in plants may cause cytoplasmic male ...sterility （CMS）, which can pro- mote outcrossing and increase fitness. However, how mitochondrial genes originate and evolve in structure and func- tion remains unclear. The rice Wild Abortive type of CMS is conferred by the mitochondrial gene WA352c （previously named WA352） and has been widely exploited in hybrid rice breeding. Here, we reconstruct the evolutionary tra- jectory of WA352c by the identification and analyses of 11 mitochondrial genomic recombinant structures related to WA352c in wild and cultivated rice. We deduce that these structures arose through multiple rearrangements among conserved mitochondrial sequences in the mitochondrial genome of the wild rice Oryza rufipogon, coupled with sub- stoichiometric shifting and sequence variation. We identify two expressed but nonfunctional protogenes among these structures, and show that they could evolve into functional CMS genes via sequence variations that could relieve the self-inhibitory potential of the proteins. These sequence changes would endow the proteins the ability to interact with the nucleus-encoded mitochondrial protein COXI1, resulting in premature programmed cell death in the anther ta- petum and male sterility. Furthermore, we show that the sequences that encode the COXll-interaction domains in these WA352c-related genes have experienced purifying selection during evolution. We propose a model for the for- mation and evolution of new CMS genes via a ＂multi-recombination/protogene formation/functionalization＂ mecha- nism involving gradual variations in the structure, sequence, copy number, and function.
Mycobacterial arabinogalactan (AG) is an essential cell wall component of mycobacteria and a frequent structural and bio‐synthetical target for anti‐tuberculosis (TB) drug development. Here, we ...report that mycobacterial AG is recognized by galectin‐9 and exacerbates mycobacterial infection. Administration of AG‐specific aptamers inhibits cellular infiltration caused by Mycobacterium tuberculosis (Mtb) or Mycobacterium bovis BCG, and moderately increases survival of Mtb‐infected mice or Mycobacterium marinum‐infected zebrafish. AG interacts with carbohydrate recognition domain (CRD) 2 of galectin‐9 with high affinity, and galectin‐9 associates with transforming growth factor β‐activated kinase 1 (TAK1) via CRD2 to trigger subsequent activation of extracellular signal‐regulated kinase (ERK) as well as induction of the expression of matrix metalloproteinases (MMPs). Moreover, deletion of galectin‐9 or inhibition of MMPs blocks AG‐induced pathological impairments in the lung, and the AG‐galectin‐9 axis aggravates the process of Mtb infection in mice. These results demonstrate that AG is an important virulence factor of mycobacteria and galectin‐9 is a novel receptor for Mtb and other mycobacteria, paving the way for the development of novel effective TB immune modulators.
SYNOPSIS
Arabinogalactan is a virulence factor of mycobacteria. Binding of galectin‐9 to mycobacterial arabinogalactan triggers matrix metalloproteinases via TAK1‐ERK signaling, which promotes mycobacterial infection and increases lung injury.
Arabinogalactan exacerbates mycobacterial infection by causing lung injury.
AG‐specific aptamers inhibit cellular mycobacterium infiltration and increase survival of infected mice or fish.
Galectin‐9 is a receptor for mycobacterial arabinogalactan and activates the TAK1‐ ERK‐MMP signaling axis.
The Arabinogalactan‐galectin‐9 interface may be exploited for the design of new host‐directed therapies.
Arabinogalactan is a virulence factor of mycobacteria. Binding of galectin‐9 to mycobacterial arabinogalactan triggers matrix metalloproteinases via TAK1‐ERK signaling, which promotes mycobacterial infection and increases lung injury.
Cerebral ischemia-reperfusion injury (IRI) is a common clinical pathological process, and it is a key step in causing further ischemic organ damage. The mechanism of cerebral IRI is still not fully ...understood, leading to a lack of effective treatment. It has been demonstrated that circular RNAs (circRNAs) can act as miRNA sponges and play an important role in regulating gene expression through a circRNA-miRNA-gene pathway. The specific role of circRNAs in the pathogenesis of cerebral IRI, however, is still unclear. Thus, in the present study, we investigated circRNA expression differences in HT22 cells with oxygen–glucose deprivation/reoxygenation (OGD/R) versus normal controls. The results from circRNA microarrays revealed that 15 circRNAs were significantly altered in the OGD/R model (p < 0.05) compared with the control group. Among them, 3 were significantly up-regulated, and the other 12 were down-regulated. Furthermore, the up-regulated expression of mmu-circRNA-015947 was verified using quantitative real-time polymerase chain reaction (qRT-PCR). Bioinformatics analysis revealed that up-regulated expression of mmu-circRNA-015947 could interact with miRNAs (mmu-miR-188-3p, mmu-miR-329-5p, mmu-miR-3057-3p, mmu-miR-5098 and mmu-miR-683) and thereby enhance target gene expression. KEGG pathway analysis predicted that mmu-circRNA-015947 may participate in apoptosis-related, metabolism-related and immune-related pathways, which are known to be involved in the pathogenesis of IRI. This research suggests that the overlapping expression of mmu-circRNA-015947 might be involved in the process of cerebral IRI and presents a novel molecular target for clinical therapy.
•CircRNA microarrays revealed that 15 circRNAs were significantly altered in the OGD/R model compared with the control group.•The up-regulated expression of mmu-circRNA-015947 was verified using qRT-PCR.•Bioinformatics analysis revealed that mmu-circRNA-015947 could interact with microRNAs and enhance target gene expression.•KEGG pathway analysis predicted that mmu-circRNA-015947 may participate in several pathways related to cerebral IRI.
Background
Epidemiological studies have identified an association between thyroid dysfunction (TD) and various kidney diseases. In this study, the prevalence of TD in type 2 diabetic mellitus (T2DM) ...patients with diabetic kidney disease (DKD) was evaluated to analyse the potential association between TD and DKD in T2DM patients.
Methodology
A total of 2108 T2DM patients from Anhui Provincial Hospital were recruited in this study. Demographic and clinical characteristics were collected from 834 T2DM patients with DKD and 1274 T2DM patients without DKD (non‐DKD). All patients were stratified into a number of groups based on UACR (urine albumin‐to‐creatinine ratio) or eGFR (estimated glomerular filtration rate): (a) A1: normoalbuminuria (<30), A2: microalbuminuria (30‐300) and A3: macroalbuminuria (>300); (b) F1: normal filtration (60‐139), F2: hyper filtration (≥140) and F3: low filtration (<60).
Results
Significant differences were observed between the non‐DKD and DKD groups (P < .05) in age, sex ratio, duration, systolic blood pressure, total cholesterol, low density lipoprotein cholesterol, serum creatinine, blood urea nitrogen, free triiodothyronine (FT3), free thyroxine (FT4) and sensitive thyrotropin hormone (sTSH). The macroalbuminuira and low filtration groups had the lowest levels of FT3 and FT4 and the highest level of sTSH, compared with all other groups (P < .0167). The prevalence of subclinical hypothyroidism in the DKD group was significantly higher than that in the non‐DKD group (χ2 = 13.92, P < .01). Logistic regression analysis showed that hypothyroidism was associated with increased UACR or reduced eGFR in T2DM patients. Compared with controls, T2DM patients with hypothyroidism exhibited a higher UACR and urinary excretion of transferrin, as well as a lower excretion of urinary Tamm‐Horsfall protein (THP) (P < .0167).
Conclusion
Subclinical hypothyroidism is more prevalent in T2DM patients with DKD than in T2DM patients without DKD. Hypothyroidism is associated with albuminuria and decreased eGFR in T2DM patients.
Objective Approximately 50% of amyotrophic lateral sclerosis (ALS) patients have cognitive and behavioural dysfunction in varying degrees and forms. Previous studies have shown that cognitive and ...behavioural changes may indicate a poor prognosis, and cognitive function gradually deteriorates over the course of disease, but the results of different studies have been inconsistent. In addition, there are relatively limited long-term follow-up studies tracking death as an endpoint. The purpose of this study was to investigate the clinical prognostic characteristics of ALS patients with cognitive behavioural changes through long-term follow-up in a cohort. Methods A total of 87 ALS patients from 2014 to 2015 in the Third Hospital of Peking University were selected and divided into a pure ALS group, an ALS with behavioural variant of frontotemporal dementia (ALS-bvFTD) group, and an ALS with cognitive and behaviour changes group. All patients were followed up for 60 months. The main end point was death and tracheotomy. Results There was no significant difference in survival curve between pure ALS and ALS with cognitive and behavioural change group, but the survival time of ALS-bvFTD group was significantly lower than the other two groups (P < 0.001). For those who was followed up to the endpoint, the survival time of the ALS-bvFTD group was significantly shorter than that of the pure ALS group (t = 5.33, p < 0.001) or the ALS with cognitive and behaviour changes group (t = 4.25, p < 0.001). The progression rate of ALS Functional Rating Scale-Revised (FRS-R) scores from recruitment to endpoint was significantly faster in the ALS-bvFTD group than in the pure ALS group (z = 2.68, p = 0.01) or the ALS with cognitive and behavioural changes group (z = 2.75, p = 0.01). There was no significant difference in survival time (t = 0.52, P = 0.60) or FRS-R score progression rate (z = 0.31, p = 0.76) between the pure ALS group and the ALS with cognitive and behavioural changes group. The total Edinburgh Cognitive and Behavioural Amyotrophic Lateral Sclerosis Screen (ECAS) score was positively correlated with survival time (r = 0.38, p = 0.01). Conclusion ALS-bvFTD patients have shorter survival time. The total ECAS score may be correlated with survival time.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
An efficient and selective electrosynthesis of phenols and anilines from arylboronic acids in aqueous ammonia is achieved in an undivided cell. By simply changing the concentration of aqueous ammonia ...and the anode potential, good yields of phenols and anilines can be obtained chemoselectively with high reaction rates. We propose that anodic oxidation could have played an important role in these transformations.
Abstract
Photochemical glycosylation has attracted considerable attention in carbohydrate chemistry. However, to the best of our knowledge, visible-light-promoted glycosylation via photoactive ...glycosyl donor has not been reported. In the study, we report a photosensitizer-free visible-light-mediated glycosylation approach using a photoactive 2-glycosyloxy tropone as the donor. This glycosylation reaction proceeds at ambient temperature to give a wide range of
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-glycosides or oligosaccharides with yields up to 99%. This method is further applied in the stereoselective preparation of various functional glycosyl phosphates/phosphosaccharides, the construction of
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-glycosides/nucleosides, and the late-stage glycosylation of natural products or pharmaceuticals on gram scales, and the iterative synthesis of hexasaccharide. The protocol features uncomplicated conditions, operational simplicity, wide substrate scope (58 examples), excellent compatibility with functional groups, scalability of products (7 examples), and high yields. It provides an efficient glycosylation method for accessing
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-glycosides and glycans.
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