Construction of spirocarbocycles via gold-catalyzed intramolecular dearomatization of naphthols.

A highly efficient, gold-catalyzed intramolecular dearomatization reaction of naphthols via 5-endo-dig cyclization is described. This facile and direct approach furnishes spirocarbocycles in excellent yields under mild conditions

Reprogramming glioblastoma multiforme cells into neurons by protein kinase inhibitors

Abstract Background Reprogramming of cancers into normal-like tissues is an innovative strategy for cancer treatment. Recent reports demonstrate that defined factors can reprogram cancer cells into pluripotent stem cells. Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor in humans. Despite multimodal therapy, the outcome for patients with GBM is still poor. Therefore, developing novel therapeutic strategy is a critical requirement. Methods We have developed a novel reprogramming method that uses a conceptually unique strategy for GBM treatment. We screened a kinase inhibitor library to find which candidate inhibitors under reprogramming condition can reprogram GBM cells into neurons. The induced neurons are identified whether functional and loss of tumorigenicity. Results We have found that mTOR and ROCK kinase inhibitors are sufficient to reprogram GBM cells into neural-like cells and “normal” neurons. The induced neurons expressed neuron-specific proteins, generated action potentials and neurotransmitter receptor-mediated currents. Genome-wide transcriptional analysis showed that the induced neurons had a profile different from GBM cells and were similar to that of control neurons induced by established methods. In vitro and in vivo tumorigenesis assays showed that induced neurons lost their proliferation ability and tumorigenicity. Moreover, reprogramming treatment with ROCK-mTOR inhibitors prevented GBM local recurrence in mice. Conclusion This study indicates that ROCK and mTOR inhibitors-based reprogramming treatment prevents GBM local recurrence. Currently ROCK-mTOR inhibitors are used as anti-tumor drugs in patients, so this reprogramming strategy has significant potential to move rapidly toward clinical trials

Facile isothermal solid acid catalyzed ionic liquid pretreatments to enhance the combined sugars production from Arundo donax Linn.

Additional file 1. Enzymatic hydrolysis of raw and water pretreated A. donax. The raw samples were exposed to the same temperature profiles as that of IL-Amberlyst pretreatments. Data are means of three replicates. Ratio = digestibility IL-Amberlyst /digestibility hot water

Anti-Skid Characteristics of Asphalt Pavement Based on Partial Tire Aquaplane Conditions

This study presented a finite element model of radial tire-asphalt pavement interaction using ABAQUS 6.14 software to investigate the skid resistance properties of asphalt pavement under partial tire aquaplane conditions. Firstly, the pavement profile datum acquired by laser scanning were imported to Finite Element Analysis (FEA) software to conduct the pavement modeling. Secondly, a steady state rolling analysis of a tire on three types of asphalt pavements under drying conditions was carried out. Variation laws of the friction coefficient of the radial tire on different pavements with different pavement textures, tire pressures, and loads on the tire were examined. Subsequently, calculation results of the steady state rolling analysis were transmitted to dynamic explicit analysis, and an aquaplane model of a radial tire on asphalt pavements was built by inputting the flow Euler grids. The tire-pavement adhesive characteristics under partial aquaplane conditions are discussed regarding the aquaplane model. Influences of the thickness of water film, the texture of asphalt pavement, and the rolling speed of the tire on the vertical pavement-tire contact force are analyzed. It is found that the vertical contact force between open graded friction course (OGFC) pavement and tire is the highest, followed by stone mastic asphalt (SMA) pavement and dense graded asphalt concrete (AC) pavement surface. The vertical contact force between tire and pavement will be greatly reduced, even with increasing speed or water film thickness. As tire speed increases from 70 km/h to 130 km/h, the tire-pavement contact force is reduced by about 25%. Moreover, when the thickness of water film increases from 0 (dry condition) to 4 mm and then to 12 mm, the vertical contact force reduced 50% and 15%, respectively, compared with under the dry contact condition. This study provided a key theoretical reference for safe driving on wet pavements

Nurse employment contracts in Chinese hospitals: impact of inequitable benefit structures on nurse and patient satisfaction

PURPOSE: Ongoing economic and health system reforms in China have transformed nurse employment in Chinese hospitals. Employment of ‘bianzhi’ nurses, a type of position with state-guaranteed lifetime employment that has been customary since 1949, is decreasing while there is an increase in the contract-based nurse employment with limited job security and reduced benefits. The consequences of inequities between the two types of nurses in terms of wages and job-related benefits are unknown. This study examined current rates of contract-based nurse employment and the effects of the new nurse contract employment strategy on nurse and patient outcomes in Chinese hospitals. METHODS: This cross-sectional study used geographically representative survey data collected from 2008 to 2010 from 181 hospitals in six provinces, two municipalities, and one autonomous region in China. Logistic regression models were used to estimate the association between contract-based nurse utilization, dissatisfaction among contract-based nurses, nurse intentions to leave their positions, and patient satisfaction, controlling for nurse, patient, and hospital characteristics. PRINCIPAL RESULTS: Hospital-level utilization of contract-based nurses varies greatly from 0 to 91%, with an average of 51%. Contract-based nurses were significantly more dissatisfied with their remuneration and benefits than ‘bianzhi’ nurses who have more job security (P <0.01). Contract-based nurses who were dissatisfied with their salary and benefits were more likely to intend to leave their current positions (P <0.01). Hospitals with high levels of dissatisfaction with salary and benefits among contract-based nurses were rated lower and less likely to be recommended by patients (P < 0.05). CONCLUSIONS: Our results suggest a high utilization of contract-based nurses in Chinese hospitals, and that the inequities in benefits between contract-based nurses and ‘bianzhi’ nurses may adversely affect both nurse and patient satisfaction in hospitals. Our study provides empirical support for the ‘equal pay for equal work’ policy emphasized by the China Ministry of Health’s recent regulations, and calls for efforts in Chinese hospitals to eliminate the disparities between ‘bianzhi’ and contract-based nurses

Single nucleotide polymorphisms of one-carbon metabolism and cancers of the esophagus, stomach, and liver in a Chinese population.

One-carbon metabolism (folate metabolism) is considered important in carcinogenesis because of its involvement in DNA synthesis and biological methylation reactions. We investigated the associations of single nucleotide polymorphisms (SNPs) in folate metabolic pathway and the risk of three GI cancers in a population-based case-control study in Taixing City, China, with 218 esophageal cancer cases, 206 stomach cancer cases, 204 liver cancer cases, and 415 healthy population controls. Study participants were interviewed with a standardized questionnaire, and blood samples were collected after the interviews. We genotyped SNPs of the MTHFR, MTR, MTRR, DNMT1, and ALDH2 genes, using PCR-RFLP, SNPlex, or TaqMan assays. To account for multiple comparisons and reduce the chances of false reports, we employed semi-Bayes (SB) shrinkage analysis. After shrinkage and adjusting for potential confounding factors, we found positive associations between MTHFR rs1801133 and stomach cancer (any T versus C/C, SB odds-ratio [SBOR]: 1.79, 95% posterior limits: 1.18, 2.71) and liver cancer (SBOR: 1.51, 95% posterior limits: 0.98, 2.32). There was an inverse association between DNMT1 rs2228612 and esophageal cancer (any G versus A/A, SBOR: 0.60, 95% posterior limits: 0.39, 0.94). In addition, we detected potential heterogeneity across alcohol drinking status for ORs relating MTRR rs1801394 to esophageal (posterior homogeneity P = 0.005) and stomach cancer (posterior homogeneity P = 0.004), and ORs relating MTR rs1805087 to liver cancer (posterior homogeneity P = 0.021). Among non-alcohol drinkers, the variant allele (allele G) of these two SNPs was inversely associated with the risk of these cancers; while a positive association was observed among ever-alcohol drinkers. Our results suggest that genetic polymorphisms related to one-carbon metabolism may be associated with cancers of the esophagus, stomach, and liver. Heterogeneity across alcohol consumption status of the associations between MTR/MTRR polymorphisms and these cancers indicates potential interactions between alcohol drinking and one-carbon metabolic pathway

Helicobacter pylori treatment and gastric cancer risk among individuals with high genetic risk for gastric cancer

ImportanceHelicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. Objective To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. Design, Setting, and Participants This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. ExposuresH pylori treatment and nutrition supplementation. Main Outcomes and Measures Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. Results Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.24-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. Conclusions and Relevance The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention

Manipulation of polarisations for broadband terahertz waves emitted from laser plasma filaments

Polarization control of broadband terahertz waves is essential for applications in many areas such as material sciences, medical and biological diagnostics, near-field communications and public securities. Conventional methods for polarization control are limited to narrow bandwidth and often with low efficiency. Here based upon theoretical and experimental studies, we demonstrate that the two-colour laser scheme in gas plasma can provide effective control of elliptically polarized terahertz waves, including their ellipticity, azimuthal angle, and chirality. This is achieved with a circularly-polarized laser at the fundamental frequency and its linearly polarized second harmonic, a controlled phase difference between these two laser components, as well as a suitable length of the laser plasma filament. A flexible control of their ellipticity and azimuthal angle is demonstrated with our theoretical model and systematic experiments. This offers a unique and flexible technique on the polarization control of broadband terahertz radiation suitable for wide applications