Addition-Rearrangement of Ketenes with Lithium N- tert-Butanesulfinamides: Enantioselective Synthesis of α,α-Disubstituted α-Hydroxycarboxylic Acid Derivatives.

Addition of the lithium salts of chiral N-substituted tert-butanesulfinamides to ketenes and subsequent silylation initiates stereoselective [2,3]-rearrangement, which affords enantioenriched α,α-disubstituted α-sulfenyloxy carboxamides through a reaction that faithfully transfers the absolute stereochemistry of the lithiated sulfinylamides to the α-carbon of the amide products. This addition-rearrangement can be performed together with ketene formation from acyl chloride in a single flask, providing a new and practical synthetic route to α-hydroxycarboxylic acid derivatives.

Divergent synthesis of polysubstituted cyclopropanes and ß-silyoxy imidates via switchable additions of N-tert-butanesulfinylimidates to acylsilanes.

Products derived from the reaction between N-tert-butanesulfinyl imidates and acylsilanes can be tuned by choosing appropriate bases and solvents. Here we show that in the presence of NaHMDS/THF, addition of enolized N-tert-butanesulfinyl imidates to acylsilanes and subsequent [1,2]-Brook rearrangement generate ß-silyloxy anion intermediates that undergo intramolecular cyclization to afford polysubstituted cyclopropanes. In the presence of tBuOK/toluene, the reaction generates ß-silyloxy imidates as the protonation products of the ß-silyloxy anion intermediates. Both reactions are highly diastereoselective.

Serum level of macrophage migration inhibitory factor predicts severity and prognosis in patients with ischemic stroke.

OBJECTIVE: To evaluate whether the macrophage migration inhibitory factor (MIF) level in serum of ischemic stroke patients was associated with their clinical severity and early outcome. METHODS: During February 2017-March 2018, consecutive patients admitted to our hospital because of first-ever ischemic stroke were identified. The prognostic value of MIF was set for predicting the outcome of these patients at discharge. The results were compared with existing methods, including National Institutes of Health Stroke Scale (NIHSS) score and validated indicators. RESULTS: 289 patients were enrolled. The serum level of all patients was determined (median: 20.6 ng/ml). At admission, 131 patients (45.3%) were evaluated as minor stroke (NIHSS < 5). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of moderate-to-high clinical severity was elevated by 5% (OR = 1.05 [95% CI: 1.01-1.09], P = 0.006) and 3% (1.03 [1.00-1.08], P = 0.02), respectively. At discharge, 82 patients (28.4%) had poor functional outcomes. The median serum level of MIF was lower in group with good outcomes than that observed in poor outcomes (19.4[15.8-24.2] vs. 24.0[19.9-29.4] ng/ml; P < 0.001). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of poor outcomes was elevated by 9% (1.09 [1.05-1.13], P < 0.001) and 6% (1.06 [1.02-1.10], P < 0.01), respectively. CONCLUSIONS: High MIF levels are independently related to the moderate to high clinical severity in ischemic stroke patients, as well as the poor outcome at discharge.

Construction of α-methoxyimidoyl ketonitrones via phosphite-mediated addition of α-keto N-tert-butanesulfinyl imidates to nitrosoarenes.

A dimethyl phosphite-mediated addition of α-keto N-tert-butanesulfinyl imidates to nitrosoarenes was developed. Nitrosoarenes were successfully used as electrophiles to trap aza-enolate intermediates that were generated from nucleophilic addition of deprotonated phosphite to α-keto N-tert-butanesulfinyl imidates and following phospha-Brook rearrangement, allowing efficient construction of ketonitrones with excellent (Z)-geometries.

Diastereoselective α-Hydroxylation of N-tert-Butanesulfinyl Imidates and N'-tert-Butanesulfinyl Amidines with Molecular Oxygen.

Diastereoselective α-hydroxylation using molecular oxygen has been achieved with chiral α-alkyl N-tert-butanesulfinyl imidates and α-aryl N'-tert-butanesulfinyl amidines. The aza-enolates generated from deprotonation of imidates/amidines can be intercepted by O2 with excellent diastereocontrol and subsequently transformed into α-hydroxylation products in the presence of the reductant trimethyl phosphite.

Long non-coding RNA TUG1 as a potential prognostic biomarker in human cancers: a meta-analysis.

LncRNA taurine upregulated gene 1 (TUG1) is reportedly dysregulated in various cancers. We performed this meta-analysis to clarify the usefulness of TUG1 as a prognostic marker in malignant tumors. The PubMed, Medline, OVID, Cochrane Library, and Web of Science databases were searched from inception to Jan 11, 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to explore the relationship between TUG1 expression and overall survival (OS). Odds ratios (ORs) were calculated to assess the association between TUG1 expression and pathological parameters. Thirteen original studies covering 1,274 cancer patients were included in this meta-analysis. The pooled HR suggested that high TUG1 expression correlated with poor OS (pooled HR=1.41, 95% CI: 1.01-1.98) in cancer types other than non-small cell lung cancer. TUG1 expression was also related to distant metastasis (OR=3.24, 95% CI: 1.18-8.93), large tumor size (OR=4.07, 95% CI: 1.08-15.28) and advanced tumor stage (OR=3.45, 95% CI: 2.19-5.44). Begg's funnel plot and Egger's test showed no evidence of obvious asymmetry for overall survival or tumor stage. Thus high TUG1 expression appears predictive of poor OS, distant metastasis, advanced tumor stage and large tumor size. This suggests TUG1 expression could serve as a biomarker for poor prognosis in cancers.

LncRNA PANDAR as a prognostic marker in Chinese cancer.

BACKGROUND: LncRNA promoter of CDKN1A antisense DNA damage activated RNA (PANDAR) is reportedly dysregulated in various cancers. We performed this meta-analysis to clarify the efficacy of PANDAR as a prognostic marker in malignant tumors. METHODS: The PubMed, Medline, OVID, Cochrane Library, and Web of Science databases were searched from inception to July 3, 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to explore the relationship between PANDAR expression and overall survival (OS). Odds ratios (ORs) were calculated to assess the association between PANDAR expression and pathological parameters. RESULTS: Eight original studies covering 1,132 cancer patients were included. The pooled HR suggested that high PANDAR expression correlated with poor OS (pooled HR=1.60, 95% CI: 1.09-2.33) in cancer patients. PANDAR expression was also related to lymph node metastasis (OR=3.26, 95% CI: 2.09-5.09), advanced tumor stage (OR=3.60, 95% CI: 2.39-5.44) and histological grade (OR=2.75, 95% CI: 1.73-4.38). Begg's funnel plot showed no evidence of obvious asymmetry for overall survival and lymph node metastasis. CONCLUSIONS: Thus high PANDAR expression appears predictive of poor OS, lymph node metastasis, advanced tumor stage and histological grade in multiple cancers. This suggests PANDAR expression could serve as a biomarker of poor prognosis in Chinese cancer patients.

Diastereoselective Electrophilic α-Hydroxyamination of N-tert-Butanesulfinyl Imidates.

Diastereoselective α-hydroxyamination of N-tert-butanesulfinyl imidates using nitrosoarenes is reported. A catalytic amount of base effectively promotes the hydroxyamination reaction of α-aryl-substituted imidates, and the resulting α-hydroxyamino imidates can be transformed into a range of synthetically useful intermediates.

Carbamoyl anion-initiated cascade reaction for stereoselective synthesis of substituted α-hydroxy-ß-amino amides.

A carbamoyl anion-initiated cascade reaction with acylsilanes and imines has been used to rapidly construct substituted α-hydroxy-ß-amino amides. The Brook rearrangement-mediated cascade allows the formation of two C-C bonds and one O-Si bond in a single pot. Using this approach, a range of α-aryl α-hydroxy-ß-amino amides has been synthesized in high yields with excellent diastereoselectivities.

An Increased Serum Level of Lipoprotein(a) Is a Predictor for Deep Vein Thrombosis in Patients with Spinal Cord Injuries.

OBJECTIVE: This prospective cohort-designed study was performed to verify whether higher levels of serum lipoprotein(a) (Lp(a)) could be a risk factor for deep vein thrombosis (DVT) in Chinese patients with spinal cord injuries (SCI). METHODS: During 2013-2014, consecutive patients with first-ever SCI were recruited and assessed for DVT using color Doppler ultrasonography for 15 days after injury and whenever clinically requested. Using logistic regression models, multivariate analyses were performed. Receiver operating characteristic curves tested the overall predicted accuracy of Lp(a) and other markers. RESULTS: In this study, 358 patients were screened in the analysis, and 279 patients with SCI were included and completed the 15-day follow-up. Fifty-five patients (19.7%) were diagnosed with DVT. Patients with SCI with DVT had significantly higher Lp(a) levels on admission (554 mg/L [interquartile range, 416-790 mg/L] vs. 158 mg/L [interquartile range, 72-252 mg/L]; P < 0.0001). Adjusted for common risk factors, multivariate analyses showed that serum Lp(a) ≥ 300 mg/L could be used independently to predict DVT (odds ratio, 10.35; 95% confidence interval [CI], 2.37-45.35; P < 0.0001). With an area under the curve (AUC) of 0.91 (95% CI, 0.86-0.94), Lp(a) showed a significantly greater discriminatory ability in predicting DVT compared with high-sensitivity C-reactive protein (AUC, 0.81; 95% CI, 0.74-0.88; P < 0.01), homocysteine (AUC, 0.78; 95% CI, 0.71-0.84; P < 0.01) and age (AUC, 0.66; 95% CI, 0.59-0.73; P < 0.001). CONCLUSIONS: Increased serum Lp(a) levels were independent predictors of DVT in patients with SCI in China, suggesting a possible role of Lp(a) in the pathogenesis of DVT.

[Data mining of simple sequence repeats in transcriptome sequences of Tibetan medicinal plant Zangyinchen Swertia mussotii].

MISA (MicroSAtelite) software was employed to screen SSRs in 68 787 contigs of Swertia mussotii transcriptome sequences. 5 610 SSRs were distributed in 5 099 contigs which accounted for 7.41% of 68 787 contigs. There are 220 kinds of SSR motifs existing in S. mussotii transcriptome. On average, SSRs occurred every 12.60 kb in length. In the SSRs, the tri-nucleotide repeat motif was the most abundant (45.99%), followed by the di-nucleotide (41.62%). AT/TA and AAT/TTA were the main types of motif in di-, tri-nucleotide repeats. The repeat numbers of SSRs which from S. mussotii transcriptome SSRs were mainly from 5 to 10 and motif length of them mostly ranged from 12 bp to 30 bp. A total of 30 651 contigs were annotated, and only 1 447 SSRs were occurred in protein-coding regions. In the six repeat motifs, tri-nucleotide repeats were the most abundant in coding regions (928). There are abundant SSRs in S. mussotii transcriptome with high frequency and various types, indicating their usefulness in theory. This research may lay the foundation for designing the targeted SSR primers and developing SSR molecular markers by mining the information of SSRs loci in S. mussotii transcriptome sequences data.

Association of CYP2J2 gene polymorphisms with ischemic stroke.

OBJECTIVE: The present study aims to investigate the relationship between CYP2J2 gene polymorphisms and ischemic stroke (IS) in a Chinese Han population. METHODS: We performed a case-control study including 300 stroke patients and 300 healthy control subjects to compare the distribution of genetic polymorphism G-50T in CYP2J2 gene. RESULTS: We found GT genotype of G-50T in CYP2J2 gene was associated with the risk for IS (13.7% vs. 7.7%, P = 0.037). After adjustment of confounders, the difference remains significant (OR = 1.890, 95% CI: 1.042-3.011). CONCLUSION: CYP2J2 gene polymorphism might increase the risk of stroke in Chinese population.