Synthesis and in vitro evaluation of novel 1,2,4-triazine derivatives as neuroprotective agents

The role of novel triazine derivatives against oxidative stress exerted by hydrogen peroxide on differentiated rat pheochromocytoma (PC12) cell line was examined and a consistent protection from H₂O₂-induced cell death, associated with a marked reduction in caspase-3 activation, was observed. Moreover, activation of NF-κB, a known regulator of a host of genes that involves in specific stress and inflammatory responses by H₂O₂, was greatly impaired by triazine pretreatment in differentiated PC12 cells. Neuroprotective effect of such compounds may represent a promising approach for treatment of neurodegenerative diseases.     

Roe deer may markedly alter forest nitrogen and phosphorus budgets across Europe

Most forests in Europe are patchily distributed within the agricultural landscape. Therefore, forest biogeochemistry in Europe cannot be understood without considering the connectivity of nutrient cycles between forest patches and fertilized cropland. In this paper, we quantified the role of roe deer, the most widespread wild ungulate in Europe, as a vector of nitrogen and phosphorus from fertilized fields to forest patches, in a typical agricultural landscape of southwestern Europe. We derived a model of nutrient transfer from a data set on deer density, landscape‐use by individual deer, and nutrient content in feces. The model shows that the magnitude of nutrient transfer is highly sensitive to the proportion of forest patches within the landscape, and to the way deer use the landscape to feed and defecate. Hence, the magnitude of nutrient transfer varies substantially across the landscape. Locally, deer may significantly fertilize the forest, transferring the equivalent of almost 20% of the atmospheric deposition of nitrogen, and the equivalent of 0.13% of the total stock of phosphorus from cropland to forest patches each year. These inputs may markedly influence the biogeochemistry of forests in the long run, and the nitrogen to phosphorus ratio available to trees and forest plants. These results highlight the significant, but, heterogeneous, role of wild ungulates in forest biogeochemistry across Europe.     

Aptamer-functionalized quantum dots as theranostic nanotools against cancer and bacterial infections: A comprehensive overview of recent trends

Aptamers (Apts) are synthetic nucleic acid ligands that can be engineered to target various molecules, including amino acids, proteins, and pharmaceuticals. Through a series of adsorption, recovery, and amplification steps, Apts are extracted from combinatorial libraries of synthesized nucleic acids. Using aptasensors in bioanalysis and biomedicine can be improved by combining them with nanomaterials. Moreover, Apt-associated nanomaterials, including liposomes, polymeric, dendrimers, carbon nanomaterials, silica, nanorods, magnetic NPs, and quantum dots (QDs), have been widely used as promising nanotools in biomedicine. Following surface modifications and conjugation with appropriate functional groups, these nanomaterials can be successfully used in aptasensing. Advanced biological assays can use Apts immobilized on QD surfaces through physical interaction and chemical bonding. Accordingly, modern QD aptasensing platforms rely on interactions between QDs, Apts, and targets to detect them. QD-Apt conjugates can be used to directly detect prostate, ovarian, colorectal, and lung cancers or simultaneously detect biomarkers associated with these malignancies. Tenascin-C, mucin 1, prostate-specific antigen, prostate-specific membrane antigen, nucleolin, growth factors, and exosomes are among the cancer biomarkers that can be sensitively detected using such bioconjugates. Furthermore, Apt-conjugated QDs have shown great potential for controlling bacterial infections such as Bacillus thuringiensis, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Campylobacter jejuni, Staphylococcus aureus, and Salmonella typhimurium. This comprehensive review discusses recent advancements in the design of QD-Apt bioconjugates and their applications in cancer and bacterial theranostics.     

Synthesis of 2-acetamido-2-deoxy-4-O-β-d-galactopyranosyl-3-O-methyl-d-glucopyranose (N-acetyl-3-O-methyllactosamine) and its benzyl α-glycoside

Benzyl 2-acetamido-2-deoxy-3-O-methyl-α-d-glucopyranoside (3) was obtained by deacetalation of its 4,6-O-benzylidene derivative (2). Compound 2 was prepared by methylation of benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-d-glucopyranoside with methyl iodide-silver oxide in N,N-dimethylformamide. Diol 3 was selectively benzoylated and p-toluenesulfonylated, to give the 6-benzoic and 6-p-toluenesulfonic esters (4 and 5, respectively). Displacement of the sulfonyl group of 5 with sodium benzoxide in benzyl alcohol afforded the 6-O-benzyl derivative (6). Glycosylation of 4 with 2,3,4,6-tetra-O-acetyl-α-d-galactopyranosyl bromide (7) in dichloromethane, in the presence of 1,1,3,3-tetramethylurea, furnished the disaccharide derivative 8. Similar glycosylation of compound 6 with bromide 7 gave the disaccharide derivative 10. O-Deacetylation of 8 and 10 afforded disaccharides 9 and 11. The structure of compound 9 was established by ¹³C-n.m.r. spectroscopy. Hydrogenolysis of the benzyl groups of 11 furnished the disaccharide 2-acetamido-2-deoxy-4-O-β-d-galactopyranosyl-3-O-methyl-d-glucopyranose (N-acetyl-3-O-methyllactosamine).     

Trehalose administration attenuates atherosclerosis in rabbits fed a high-fat diet

Disruption of macrophage autophagy is a major contributor to macrophage dysfunction and subsequent inflammation leading to atherosclerosis. Trehalose is a natural disaccharide that is able to induce macrophage autophagy-lysosomal biogenesis and reduce inflammation. Here, we studied the efficacy of intravenous trehalose administration in reducing atherosclerotic plaque burden in high-cholesterol-fed rabbits. Adult male New Zealand white Rabbits were fed with a high-fat diet containing 1% cholesterol for 8 weeks followed by a cholesterol-free diet for the next 4 weeks. In the latter 4-week phase of the cholesterol-free diet, one group received intravenous trehalose solution at a dose of 350 mg/kg, three times per week. In the control group, an equivalent volume of PBS (3 mL) was administered with the same protocol. At the end of the 12th week of the study, all rabbits were anesthetized and aortic arch sections were collected followed by hematoxylin and eosin staining and assessment of plaque grading. Fasting serum lipids were also measured using routine enzymatic methods. At the end of the 12th week, there were no significant differences in the body weight and blood lipids between the control- and trehalose-treated groups. Intravenous trehalose administration significantly attenuated atherosclerotic plaque development as revealed by reduced plaque grading ( P = 0.048) and intima/media thickness ratio ( P = 0.017). Intimal thickening was also found to be reduced in the trehalose versus control group, though this reduction did not reach statistical significance. The present study provided evidence as to the efficacy of short-term intravenous trehalose administration in regressing atherosclerotic plaque in high-fat-fed rabbits.     

Adjunctive Corticotherapy for Community Acquired Pneumonia: A Systematic Review and Meta-Analysis

Background

Community-acquired pneumonia (CAP) induces lung and systemic inflammation, leading to high morbidity and mortality. We systematically reviewed the risks and benefits of adjunctive corticotherapy in the management of patients with CAP.

Methods

We systematically searched Pubmed, Embase and the Cochrane Library for randomized controlled trials comparing adjunctive corticotherapy and antimicrobial therapy with antimicrobial therapy alone in patients with CAP. The primary outcome was 30-day mortality. Secondary outcomes were length of hospital stay, time to clinical stability and severe complications.

Results

14 trials (2077 patients) were included. The reported 30-day mortality was 7.9% (80/1018) among patients treated with adjunctive corticotherapy versus 8.3% (85/1028) among patients treated with antimicrobial therapy alone (RR 0.84; 95%CI 0.55 to1.29). Adjunctive corticotherapy was associated with a reduction of severe complications (RR 0.36; 95%CI 0.23 to 0.56), a shorter length of stay (9.0 days; 95%CI 7.6 to 10.7 vs 10.6 days; 95%CI 7.4 to 15.3) and a shorter time to clinical stability (3.3 days; 95% CI 2.8 to 4.1 vs 4.3 days; 95%CI 3.6 to 5.1). The risk of hyperglycemia was higher among patients treated with adjunctive corticotherapy (RR 1.59; 95%CI 1.06 to 2.38), whereas the risk of gastro-intestinal bleeding was similar (RR 0.83; 95%CI 0.35 to 1.93). In the subgroup analysis based on CAP severity, a survival benefit was found among patients with severe CAP (RR 0.47; 95%CI 0.23 to 0.96).

Conclusion

Adjunctive corticotherapy is associated with a reduction of length of stay, time to clinical stability, and severe complications among patients with CAP, but the effect on mortality remains uncertain.     

鹞落坪树生地衣群落数量分类及多样性

采用主成分分析(PCA)对鹞落坪国家级自然保护区森林树生地衣进行了群落排序;应用Spearman 秩相关检对22种地衣进行了种间关联分析;以地衣多样性、相似性和均匀度等指数,对各地衣群落进行了比较.根据主成分分析结果并结合生境特征,保护区树生地衣形成了6种群落.Spearman秩相关检表明39个种对呈显著正相关,其中1...