抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

The design and implementation of cascade reactions is a challenging facet of organic chemistry, yet one that can impart striking novelty, elegance, and efficiency to synthetic strategies. The application of cascade reactions to natural products synthesis represents a particularly demanding task, but the results can be both stunning and instructive. This Review highlights selected examples of cascade reactions in total synthesis, with particular emphasis on recent applications therein. The examples discussed herein illustrate the power of these processes in the construction of complex molecules and underscore their future potential in chemical synthesis.

Cascade reactions in total synthesis.

Since the beginning of the century, the mammalian sirtuin protein family (comprising SIRT1-SIRT7) has received much attention for its regulatory role, mainly in metabolism and ageing. Sirtuins act in different cellular compartments: they deacetylate histones and several transcriptional regulators in the nucleus, but also specific proteins in other cellular compartments, such as in the cytoplasm and in mitochondria. As a consequence, sirtuins regulate fat and glucose metabolism in response to physiological changes in energy levels, thereby acting as crucial regulators of the network that controls energy homeostasis and as such determines healthspan.

/pdf/sirtuins-as-regulators-of-metabolism-and-healthspan-jvf88hfgf7.pdf

Sirtuins as regulators of metabolism and healthspan

The Diels-Alder reaction has both enabled and shaped the art and science of total synthesis over the last few decades to an extent which, arguably, has yet to be eclipsed by any other transformation in the current synthetic repertoire. With myriad applications of this magnificent pericyclic reaction, often as a crucial element in elegant and programmed cascade sequences facilitating complex molecule construction, the Diels-Alder cycloaddition has afforded numerous and unparalleled solutions to a diverse range of synthetic puzzles provided by nature in the form of natural products. In celebration of the 100th anniversary of Alder's birth, selected examples of the awesome power of the reaction he helped to discover are discussed in this review in the context of total synthesis to illustrate its overall versatility and underscore its vast potential which has yet to be fully realized.

https://www.ch.ic.ac.uk/local/organic/pericyclic/DA.pdf

The Diels--Alder reaction in total synthesis.

Nonalcoholic fatty liver disease (NAFLD) is an abnormal liver metabolism often observed with insulin resistance and metabolic syndrome. Calorie restriction is a useful treatment for NAFLD and reportedly prolongs the life spans of several species in which sirtuin plays an important role. In this study, we examined whether the activation of SIRT1, a mammalian ortholog of sirtuin, may ameliorate the development of NAFLD. Monosodium glutamate (MSG) mice, which exhibited obesity and insulin resistance, were treated with SRT1720, a specific SIRT1 activator from the age of 6-16 wk. Sixteen-week-old MSG mice exhibited increased liver triglyceride content and elevated levels of aminotransferase. SRT1720 treatment significantly reduced these levels without affecting body weight or food intake. These results suggested that the administration of SRT1720 ameliorated the development of NAFLD in MSG mice. The expressions of lipogenic genes, such as sterol regulatory element-binding protein-1c, acetyl-CoA carboxylase, and fatty acid synthase, and the serum lipid profiles, including free fatty acids, were elevated in MSG mice and were reduced by SRT1720 treatment. SRT1720 treatment also reduced the expressions of lipogenic genes in cultured HepG2 cells. Furthermore, SRT1720 treatment decreased the expressions of marker genes for oxidative stress and inflammatory cytokines in the liver of MSG mice. Taken together, SRT1720 treatment may reduce liver lipid accumulation, at least in part, by directly reducing the expressions of lipogenic genes. The reduction of oxidative stress and inflammation may also be involved in the amelioration of NAFLD.

https://www.physiology.org/doi/pdf/10.1152/ajpendo.90997.2008

Treatment with SRT1720, a SIRT1 activator, ameliorates fatty liver with reduced expression of lipogenic enzymes in MSG mice

Recent advances in the total synthesis of steroids via intramolecular cycloaddition reactions

Aerobic oxidation of α-hydroxycarbonyls catalysed by trichlorooxyvanadium: efficient synthesis of α-dicarbonyl compounds

La reaction de couplage, catalysee par le palladium, de derives halogenes de nucleosides avec un aryletain possedant un groupement boronique a lieu chimioselectivement sur la liaison C-Sn plutot que sur la liaison C-B, pour donner des derives bores de nucleosides avec de bons rendements

New method for the synthesis of boron-10 containing nucleoside derivatives for neutron-capture therapy via palladium-catalyzed reaction

A remarkable substituent effect by the tert-butyldimethylsiloxy group on the enantioselectivity of the tandem asymmetric epoxidation and enantiospecific ring expansion of 2-[2-(tert-butyldimethylsiloxy)-4-methylphenyl]-2-cyclopropylideneethanol (18), affording (S)-(-)-2-[2-(tert-butyldimethylsiloxy)-4-methylphenyl]-2-hydroxymethylcyclobutanone (21) in high yield and high enantiomeric excess, was observed. This enabled us to accomplish a concise and highly enantioselective total synthesis of (-)-debromoaplysin (2) and (-)-aplysin (1), providing a new and general strategy for the enantioselective synthesis of biologically important substances having the dihydrobenzofuran framework

A remarkable substituent effect on the enantioselectivity of tandem asymmetric epoxidation and enantiospecific ring expansion of cyclopropylidene alcohols: a new enantiocontrolled synthesis of (-)-debromoaplysin and (-)-aplysin

Hideo Nemoto

Papers

Treatment with SRT1720, a SIRT1 activator, ameliorates fatty liver with reduced expression of lipogenic enzymes in MSG mice

Recent advances in the total synthesis of steroids via intramolecular cycloaddition reactions

Aerobic oxidation of α-hydroxycarbonyls catalysed by trichlorooxyvanadium: efficient synthesis of α-dicarbonyl compounds

New method for the synthesis of boron-10 containing nucleoside derivatives for neutron-capture therapy via palladium-catalyzed reaction

A remarkable substituent effect on the enantioselectivity of tandem asymmetric epoxidation and enantiospecific ring expansion of cyclopropylidene alcohols: a new enantiocontrolled synthesis of (-)-debromoaplysin and (-)-aplysin