During the COVID-19 era, Chinese hospitals have developed a system that enables vulnerable cancer patients to continue to receive high-quality medical care, optimising their survival whilst ...protecting them. This includes use of digital quick codes, fever clinics and optimal scheduling. We wish to share our experiences working with patients during the pandemic.
Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram‐negative bacteria. To explore the antigenic ...properties of A. baumannii LPS, four Kdo‐containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α‐Kdo‐(2→5)‐Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α‐stereocontrolled coupling with 5,7‐O‐di‐tert‐butylsilylene or 5‐O‐benzoyl protected Kdo thioglycosides and 2‐azido‐2‐deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5‐branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.
Four inner core oligosaccharides from the lipopolysaccharide (LPS) of A. baumannii strain ATCC 17904 were chemically synthesized (see structures). Antigenic investigation indicated that the 4,5‐branched Kdo trisaccharide, a common inner core structure of A. baumannii LPS, is a potential antigenic epitope that could be used for further immunological research to develop diagnostic tools or vaccines against A. baumannii.
Recent evidence highlights long noncoding RNAs (lncRNA) as crucial regulators of cancer biology that contribute to essential cancer cell functions such as cell proliferation, apoptosis, and ...metastasis. In non-small cell lung cancer (NSCLC), several lncRNAs' expressions are misregulated and have been nominated as critical actors in NSCLC tumorigenesis. LncRNA ANRIL was first found to be required for the PRC2 recruitment to and silencing of p15(INK4B), the expression of which is induced by the ATM-E2F1 signaling pathway. Our previous study showed that ANRIL was significantly upregulated in gastric cancer, and it could promote cell proliferation and inhibit cell apoptosis by silencing of miR99a and miR449a transcription. However, its clinical significance and potential role in NSCLC is still not documented. In this study, we reported that ANRIL expression was increased in NSCLC tissues, and its expression level was significantly correlated with tumor-node-metastasis stages and tumor size. Moreover, patients with high levels of ANRIL expression had a relatively poor prognosis. In addition, taking advantage of loss-of-function experiments in NSCLC cells, we found that knockdown of ANRIL expression could impair cell proliferation and induce cell apoptosis both in vitro and vivo. Furthermore, we uncover that ANRIL could not repress p15 expression in PC9 cells, but through silencing of KLF2 and P21 transcription. Thus, we conclusively demonstrate that lncRNA ANRIL plays a key role in NSCLC development by associating its expression with survival in patients with NSCLC, providing novel insights on the function of lncRNA-driven tumorigenesis.
The tuning effect of C3‐ester groups on the glycosylation stereochemistry of L‐rhamnopyranose (L‐Rha) ethyl thioglycoside donors is described. On one hand, the L‐Rha thioglycoside donors carrying ...3‐O‐arylcarbonyl or levulinoyl group undergo highly α‐selective glycosylation to afford a wide variety of α‐L‐rhamnoside products in high chemical yields. On the other hand, the glycosylation of the 3‐O‐4‐nitropicoloyl and 2‐pyrazinecarbonyl group substituted L‐Rha thioglycosides displays β‐stereoselectivity. Only or predominant β anomeric products are obtained when these L‐Rha donors couple with the primary or reactive secondary acceptors, while the β‐selectivity may decrease significantly when these donors react with less reactive secondary alcohols. The synthetic utility of the newly developed α‐ and β‐directing L‐Rha donors 1h and 1e has been demonstrated by the efficient synthesis of a structurally unique trisaccharide 9, which is derived from the cell wall polysaccharide of Sphaerotilus natans.
The tuning effect of C3‐ester groups on the glycosylation stereochemistry of Lrhamnopyranose (L‐Rha) ethyl thioglycosides is described. The 3‐O‐arylcarbonyl or levulinoyl carrying L‐Rha thioglycosides undergo highly α‐selective glycosylation while the glycosylation of the 3‐O‐4‐nitropicoloyl and 2‐pyrazinecarbonyl L‐Rha thioglycosides displays β‐stereoselectivity
Objective
Complications related to triceps after total elbow arthroplasty (TEA) have become a major surgical concern. The triceps‐preserving approach has the advantage of not disturbing the insertion ...of triceps but is disadvantaged by the reduced exposure of the elbow joint. The aim of this study was to investigate the clinical and radiological outcomes of TEA with a triceps‐preserving approach and to compare the outcomes of TEA to treat arthropathy with that of TEA to treat acute distal humerus fracture.
Methods
From January 2010 to December 2018, 23 patients undergoing primary TEAs were retrospectively reviewed with a mean follow‐up time of 92.6 months (range, 52–136 months). Each TEA was performed using the triceps‐preserving approach with a semi‐constrained Coonrad–Morrey prosthesis. Patient demographics, range of motion (ROM), pain visual analogue scale (VAS), and triceps strength (Medical Research Council MRC scale) were compared before and after surgery. The Mayo Elbow Performance Score (MEPS), Disabilities of the Arm, Shoulder, and Hand (DASH) score, radiographic outcome, and complications were evaluated at follow‐up.
Results
In total, seven males and 16 females were included in this study, with a mean age of 66.1 years (range:46–85 years). By the last follow‐up, pain had been significantly relieved in all patients. The average MEPS in the arthropathy group and fracture group were 90.8 ± 10.3 points (range: 68–98 points) and 91.7 ± 0.4 (range: 76–100 points), respectively. The average DASH of the arthropathy group and fracture group was 37.3 ± 18.8 points (range: 18–52 points) and 38.4 ± 20.1 (range: 16–60 points). At the last follow‐up after surgery, the mean flexion arcs in the arthropathy group and fracture group were 100.4° ± 24.1° and 97.8° ± 28.1°, respectively. The mean pro‐supination arcs in the arthropathy group and fracture group were 142.4° ± 15.2° and 139.2° ± 17.5°, respectively. There were no significant differences in clinical outcomes between the two groups (P ≥ 0.05). Triceps strength was normal (MRC grade V) in 15 elbows and good in eight elbows. None of the cases experienced weakness of the triceps strength, infection, periprosthetic fractures, or prosthesis breakage.
Conclusions
The clinical and radiographical outcomes of TEA with the triceps‐preserving approach were satisfactory in patients with distal humerus fracture, osteoarthritis and rheumatoid arthritis.
Clinical and radiographic outcomes of total elbow arthroplasty with triceps‐preserving approach: with minimal 4‐years follow‐up.
Long noncoding RNAs are involved in diseases including cancer. Here, we reported that ANRIL (CDKN2B-AS1), a 3.8-kb long noncoding RNA, recruiting and binding to PRC2, was generally upregulated in ...human gastric cancer (GC) tissues. In a cohort of 120 GC patients, the higher expression of ANRIL was significantly correlated with a higher TNM stage (P=0.041) and tumor size (P=0.001). Multivariate analyses revealed that ANRIL expression served as an independent predictor for overall survival (P=0.036). Further experiments revealed that ANRIL knockdown significantly repressed the proliferation both in vitro and in vivo. We also showed that E2F1 could induce ANRIL and ANRIL-mediated growth promotion is in part due to epigenetic repression of miR-99a/miR-449a in Trans (controlling the targets--mTOR and CDK6/E2F1 pathway) by binding to PRC2, thus forming a positive feedback loop, continuing to promote GC cell proliferation. To our knowledge, this is the first report showed that the role of ANRIL in the progression of GC and ANRIL could crosstalk with microRNAs in epigenetic level. Our results suggest that ANRIL, as a growth regulator, may serve as a candidate prognostic biomarker and target for new therapies in human gastric cancer.
An efficient α‐sialylation methodology for various primary, secondary, and tertiary alcohol acceptors has been developed. The sialic acid ethyl thioglycoside 1b, bearing a 4‐nitropicoloyl moiety as ...the stereodirecting group at the C4 position, was utilized as the glycosyl donor, and the sialylation reaction was activated with N‐iodosuccinimide and catalytic triflic acid in a 1:1 mixture of dichloromethane/acetonitrile as solvent. The method was successfully applied to the stereocontrolled synthesis of protected trisaccharide 11 found in the repeating unit of serotype Ia Group B Streptococcus capsular polysaccharide.
The sialic acid ethyl thioglycoside donor, bearing a 4‐nitropicoloyl moiety as the stereodirecting group at the C4 position, can successfully achieve highly α‐sialylation with various acceptors. The method has been extended to the stereocontrolled synthesis of the protected trisaccharide found in the repeating unit of serotype Ia Group B Streptococcus capsular polysaccharide.
MicroRNAs (miRNAs) are short, non-coding RNAs (~22 nt) that play important roles in the pathogenesis of human diseases by negatively regulating gene expression. Although miR-196a has been implicated ...in several other cancers, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of the present study was to examine the expression pattern of miR-196a in NSCLC and its clinical significance, as well as its biological role in tumor progression.
Expression of miR-196a was analyzed in 34 NSCLC tissues and five NSCLC cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The effect of DNA methylation on miR-196a expression was investigated by 5-aza-2-deoxy-cytidine treatment and bisulfite sequencing. The effect of miR-196a on proliferation was evaluated by MTT and colony formation assays, and cell migration and invasion were evaluated by transwell assays. Analysis of target protein expression was determined by western blotting. Luciferase reporter plasmids were constructed to confirm the action of miR-196a on downstream target genes, including HOXA5. Differences between the results were tested for significance using Student's t-test (two-tailed).
miR-196a was highly expressed both in NSCLC samples and cell lines compared with their corresponding normal counterparts, and the expression of miR-196a may be affected by DNA demethylation. Higher expression of miR-196a in NSCLC tissues was associated with a higher clinical stage, and also correlated with NSCLC lymph-node metastasis. In vitro functional assays demonstrated that modulation of miR-196a expression affected NSCLC cell proliferation, migration and invasion. Our analysis showed that miR-196a suppressed the expression of HOXA5 both at the mRNA and protein levels, and luciferase assays confirmed that miR-196a directly bound to the 3'untranslated region of HOXA5. Knockdown of HOXA5 expression in A549 cells using RNAi was shown to promote NSCLC cell proliferation, migration and invasion. Finally, we observed an inverse correlation between HOXA5 and miR-196a expression in NSCLC tissues.
Our findings indicate that miR-196a is significantly up-regulated in NSCLC tissues, and regulates NSCLC cell proliferation, migration and invasion, partially via the down-regulation of HOXA5. Thus, miR-196a may represent a potential therapeutic target for NSCLC intervention.
We describe in this paper the development of a novel diastereoselective cyclic imine cycloaddition strategy to access the polyhydroxylated indolizidine skeleton and its application in the concise ...syntheses of (+)-/(-)-lentiginosines and (-)-2-epi-steviamine.
An efficient synthesis of a structurally congested tetrasaccharide portion from the cellulosome produced by Clostridium thermocellum has been accomplished through a stepwise glycosylation strategy. ...The key steps for the synthesis include the stereocontrolled construction of a range of challenging 1,2‐cis glycosidic linkages. The 5‐O‐(2‐quinolinecarbonyl) substituted D‐galactofuranosyl thioglycoside 2, 4,6‐O‐benzylidene protected 2‐azido‐2‐deoxyglucose thioglycoside 3 c, and 4,6‐O‐benzylidene protected D‐galactopyranosyl thioglycoside 4 were employed as glycosyl donors, respectively, for the high‐yielding and stereoselective formation of the corresponding 1,2‐cis‐α‐Galf, α‐GlcNAc, and α‐Galp linkages.
Carbohydrates: The preparation of structurally congested tetrasaccharide fragment from the cellulosome produced by Clostridium thermocellum is described. The key steps for the synthesis include the stereocontrolled construction of a set of challenging 1,2‐cis glycosidic linkages.
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