One-Pot Selective Saturation and Functionalization of Heteroaromatics Leading to Dihydropyridines and Dihydroquinolines.

A one-pot regioselective two C-C-bond-forming dearomatization of pyridines and quinolines is disclosed. Two 3,4-betaines are identified for the first time as very useful organic synthons in heterocyclic chemistry. Furthermore, the chemical reactivity of the prepared trifluoromethyl ketones, a new type of push-pull enones, has been explored to develop straightforward methods for their functionalization. This protocol represents a breakthrough in the dearomatization of heteroaromatics as both the selective saturation and functionalization of heteroaromatics are achieved in high efficiency by the attachment of two substituents, including the valuable trifluoromethyl ketone group.

A novel nomogram integrating body composition and inflammatory-nutritional markers for predicting postoperative complications in patients with adhesive small bowel obstruction.

Background: Postoperative complications in adhesive small bowel obstruction (ASBO) significantly escalate healthcare costs and prolong hospital stays. This study endeavors to construct a nomogram that synergizes computed tomography (CT) body composition data with inflammatory-nutritional markers to forecast postoperative complications in ASBO. Methods: The study's internal cohort consisted of 190 ASBO patients recruited from October 2017 to November 2021, subsequently partitioned into training (n = 133) and internal validation (n = 57) groups at a 7:3 ratio. An additional external cohort comprised 52 patients. Body composition assessments were conducted at the third lumbar vertebral level utilizing CT images. Baseline characteristics alongside systemic inflammatory responses were meticulously documented. Through univariable and multivariable regression analyses, risk factors pertinent to postoperative complications were identified, culminating in the creation of a predictive nomogram. The nomogram's precision was appraised using the concordance index (C-index) and the area under the receiver operating characteristic (ROC) curve. Results: Postoperative complications were observed in 65 (48.87%), 26 (45.61%), and 22 (42.31%) patients across the three cohorts, respectively. Multivariate analysis revealed that nutrition risk score (NRS), intestinal strangulation, skeletal muscle index (SMI), subcutaneous fat index (SFI), neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR) were independently predictive of postoperative complications. These preoperative indicators were integral to the nomogram's formulation. The model, amalgamating body composition and inflammatory-nutritional indices, demonstrated superior performance: the internal training set exhibited a 0.878 AUC (95% CI, 0.802-0.954), 0.755 accuracy, and 0.625 sensitivity; the internal validation set displayed a 0.831 AUC (95% CI, 0.675-0.986), 0.818 accuracy, and 0.812 sensitivity. In the external cohort, the model yielded an AUC of 0.886 (95% CI, 0.799-0.974), 0.808 accuracy, and 0.909 sensitivity. Calibration curves affirmed a strong concordance between predicted outcomes and actual events. Decision curve analysis substantiated that the model could confer benefits on patients with ASBO. Conclusion: A rigorously developed and validated nomogram that incorporates body composition and inflammatory-nutritional indices proves to be a valuable tool for anticipating postoperative complications in ASBO patients, thus facilitating enhanced clinical decision-making.

New anhydrous proton exchange membrane for intermediate temperature proton exchange membrane fuel cells.

Herein, we study the preparation and characterization of a new kind of proton exchange membrane. In the proton-conducting membrane of poly(vinylidene fluoride) (PVDF)/poly(ethylene oxide) (PEO)/dodecyl benzenesulfonic acid (DBS-H), we use PEO as "proton solvent" due to its flexible molecular chain. Moreover, the electronegativity of the O atom on PEO may be used to attract protons under anhydrous conditions. The membranes are thermally stable up to 200 °C with less than 3 % mass loss. At 150 °C, without extra humidification, the proton conductivity of 60 % PVDF/22 % PEO/18 % DBS-H membrane is approximately 10 (-3) S cm(-1).

N-acetylgalactosamine-decorated nanoliposomes for targeted delivery of paclitaxel to hepatocellular carcinoma.

In this study, we designed and developed a novel asialoglycoprotein receptor (ASGPR)-targeted PEGylated paclitaxel (PTX) nanoliposome for hepatocellular carcinoma (HCC). N-acetylgalactosamine with α configuration (Tn) was synthesized and used as the active targeting ligand. Notably, Tn modified nanoliposomes loaded with PTX (Tn-Lipo-PTX) showed a narrow distribution (PDI = 0.18-0.20) with 74 ± 0.36 nm of average sizes. Tn-Lipo-PTX has a high encapsulation efficiency of more than 93.0% and 13% of drug loading (DL). Compared with no targeted Con-Lipo-PTX, Tn-Lipo-PTX showed lower and sustained release characteristic in PBS in vitro. Tn targeting ASGPR was confirmed by HepG-2 cells uptake experiment by fluorescence microscopy analysis. Tn-Lipo-PTX accumulated in HepG-2 cells and this process was inhibited by adding Tn ligand, supporting receptor-mediated endocytosis mechanism. MTT assays was implemented in four cell lines. Tn-Lipo-PTX exhibited superior inhibition against ASGPR on over-expressing HepG-2 (IC50 = 1.93 nM). The cell cycle experiments showed that Tn-Lipo-PTX could efficiently increase the percentage of cells arrest in the G2/M phase. Through western blotting analysis, the ß-tubulin and cyclin B1 expression in the Tn-Lipo-PTX group were significantly higher compared with other groups and the CDK1 was down-regulated compared with PTX group, which indicated that targeting liposome delivery system could not only change periodic proteins expression, but also improve the killing effect of PTX on hepatocarcinoma cell. Tn-installed PEGylated nanoliposomes have a great potential for targeted cancer chemotherapy.

Novel mitochondrial C15620A variant may modulate the phenotype of mitochondrial G11778A mutation in a Chinese family with Leigh syndrome.

We report a case of 3-year-old boy who presented with Leigh syndrome but carried a mitochondrial G11778A mutation in the fourth subunit of the NADH dehydrogenase gene (MTND4). Additional to G11778A mutation, a novel C15620A variant was detected, which resulted in the conversion from leucine to isoleucine in the mitochondrial cytochrome b gene. As G11778A mutation is the most common mutation associated with Leber's hereditary optic neuropathy (LHON), given the unusual phenotype, the C15620A mutation was postulated to influence the pathogenicity of the G11778A mutation. This case further expands the clinical spectrum associated with the primary G11778A LHON mutation.

Impact of a better persistence with antihypertensive agents on ischemic stroke outcomes for secondary prevention.

BACKGROUND: The efficacy of antihypertensive (AH) treatment after stroke has been investigated in several randomized clinical trials. However, non-adherence to AH medication is common for stroke patients in "real world" setting. The purpose of this study was to assess the impact of persistence with AH agents on ischemic stroke (IS) outcomes. METHODS AND RESULTS: Using the China National Stroke Registry, we analyzed data from 8409 IS patients with hypertension. Persistence with AH therapy (high persistence ≥75%, low persistence <75%) was measured by patient self-report at 3, 6, and 12 months after stroke. Multivariate logistic regression model was used to assess the relationship between persistence and IS outcomes (stroke recurrence, combined vascular events and death) at 12 months. Of the 8409 patients in this study, 40.0% were female and the mean age at study entry was 66.7 years. 31.6% of patients had high persistence with AH drugs, and 68.4% had low persistence during 1 year after stroke onset. High persistence with AH drugs significantly decreased the risk of stroke recurrence (odds ratio, 0.78; 95% CI, 0.68 to 0.89), combined vascular events (0.71; 0.63-0.81) and death (0.44; 0.36-0.53) compared with low persistence. CONCLUSIONS: Our study reinforces the benefits of AH medications in routine clinical practice and highlights the importance of persistence with AH therapy among IS patients known to be hypertensive within the first year of an event.

Non-high-density lipoprotein cholesterol vs low-density lipoprotein cholesterol as a risk factor for ischemic stroke: a result from the Kailuan study.

OBJECTIVES: To compare the predictive value of serum low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol levels for ischemic stroke in the Chinese population. METHODS: We performed a four-year cohort study of 95 778 men and women, aged 18-98 years, selected from the Kailuan study (2006-2007). Baseline LDL cholesterol levels were estimated using direct test method. Total cholesterol levels were estimated using endpoint test method. The predictive values of LDL cholesterol and non-HDL cholesterol for ischemic stroke were compared. RESULTS: During the follow-up period, there were 1153 incident cases of ischemic stroke. The hazard ratio (HR) for ischemic stroke in the top quintile of LDL cholesterol was the highest among five quintiles (HR: 1·25; 95% confidence interval (CI), 1·01-1·53). The HR in the top quintile of non-HDL cholesterol for ischemic stroke was also the highest among five quintiles (HR: 1·53; 95% CI, 1·24-1·88). Analysis of trends showed a significant positive relationship between ischemic stroke incidence and serum LDL cholesterol level, and non-HDL cholesterol level, respectively (both P < 0·05). The area under the curve of LDL cholesterol and non-HDL cholesterol for ischemic stroke was 0·51 and 0·56, respectively (P < 0·05 for the difference). CONCLUSIONS: Serum Non-HDL cholesterol level is a stronger predictor for the risk of ischemic stroke than serum LDL cholesterol level in the Chinese population.

[Epidemiological feature of hepatitis B in Zaozhuang City, Shandong Province].

OBJECTIVE: To study the prevalence and the epidemiological feature of hepatitis B in the population of Zaozhuang and the seroepidemiology of hepatitis B virus infection. METHODS: HBsAg, anti-HBs and anti-HBc were detected in 963 sera collected from 312 families by RIA, which were selected by multistage and stratified cluster sampling. RESULTS: The results indicated that the standardized positive rates of HBsAg, anti-HBs and anti-HBc were 7.08%, 37.56% and 41.35%, respectively and the standardized prevalence rate of hepatitis B virus infection was 44.37%. The positive rate of HBsAg was higher in male subjects and in the urban area groups than those in female subjects (P<0.05) and in rural area groups (P<0.01), respectively. There was no significant difference in the positive rate of HBsAg among all age groups and occupation groups (P>0.05). The positive rates of anti-HBs and anti-HBc and infective rate of hepatitis B virus increased with age. The infective rate of hepatitis B virus was higher in male subjects and in rural area groups than those in female subjects (P<0.05) and in urban area groups (P<0.05), respectively. CONCLUSIONS: The HBV infective rate of population was higher in Zaozhuang city; measures of prevention and control should be taken actively and effectively.