Alisol A attenuates high‐fat‐diet‐induced obesity and metabolic disorders via the AMPK/ACC/SREBP‐1c pathway

Obesity and its associated metabolic disorders such as diabetes, hepatic steatosis and chronic heart diseases are affecting billions of individuals. However there is no satisfactory drug to treat such diseases. In this study, we found that alisol A, a major active triterpene isolated from the Chinese traditional medicine Rhizoma Alismatis, could significantly attenuate high‐fat‐diet‐induced obesity. Our biochemical detection demonstrated that alisol A remarkably decreased lipid levels, alleviated glucose metabolism disorders and insulin resistance in high‐fat‐diet‐induced obese mice. We also found that alisol A reduced hepatic steatosis and improved liver function in the obese mice model.In addition, protein expression investigation revealed that alisol A had an active effect on AMPK/ACC/SREBP‐1c pathway. As suggested by the molecular docking study, such bioactivity of alisol A may result from its selective binding to the catalytic region of AMPK.Therefore, we believe that Alisol A could serve as a promising agent for treatment of obesity and its related metabolic diseases.     

中国龙胆属植物研究(四)

龙胆属Gentiana (Tourn) L.是Tourneferot (1700)为纪念传说中的Illyria国王Gentius而建立的,对它作了描述,绘有墨线图。林奈在"植物属志"(1737),"植物种志"(1753)承认了该属,并重新进行了描述,记载23种。     

Long COVID and its Management

The pandemic of COVID-19 is the biggest public health crisis in 21^st Century. Besides the acute symptoms after infection, patients and society are also being challenged by the long-term health complications associated with COVID-19, commonly known as long COVID. While health professionals work hard to find proper treatments, large amount of knowledge has been accumulated in recent years. In order to deal with long COVID efficiently, it is important for people to keep up with current progresses and take proactive actions on long COVID. For this purpose, this review will first introduce the general background of long COVID, and then discuss its risk factors, diagnostic indicators and management strategies. This review will serve as a useful resource for people to understand and prepare for long COVID that will be with us in the foreseeable future.     

Lack of enhanced spinal regeneration in Nogo-deficient mice

The failure of regeneration of severed axons in the adult mammalian central nervous system is thought to be due partly to the presence of endogenous inhibitors of axon regeneration. The nogo gene encodes three proteins (Nogo-A, -B, and -C) that have been proposed to contribute to this inhibition. To determine whether deletion of nogo enhances regenerative ability, we generated two lines of mutant mice, one lacking Nogo-A and -B but not -C (Nogo-A/B mutant), and one deficient in all three isoforms (Nogo-A/B/C mutant). Although Nogo-A/B-deficient myelin has reduced inhibitory activity in a neurite outgrowth assay in vitro, tracing of corticospinal tract fibers after dorsal hemisection of the spinal cord did not reveal an obvious increase in regeneration or sprouting of these fibers in either mouse line, suggesting that elimination of Nogo alone is not sufficient to induce extensive axon regeneration.     

Peptide nanowires for coordination and signal transduction of peroxidase biosensors to carbon nanotube electrode arrays

A strategy of metallizing peptides to serve as conduits of electronic signals that bridge between a redox enzyme and a carbon-nanotube electrode has been developed with enhanced results. In conjunction, a protocol to link the biological elements to the tips of carbon nanotubes has been developed to optimize contact and geometry between the redox enzyme and the carbon nanotube electrode array. A peptide nanowire of 33 amino acids, comprised of a leucine zipper motif, was mutated to bind divalent metals, conferring conductivity into the peptide. Reaction between a thiolate of the peptide with the sulfenic acid of the NADH peroxidase enzyme formed a peptide-enzyme assembly that are fully primed to transduce electrons out of the enzyme active site to an electrode. Scanning electron microscopy shows immobilization and linking of the assembly specifically to the tips of carbon nanotube electrodes, as designed. Isothermal titration calorimetry and mass spectrometry indicate a binding stoichiometry of at least three metals bound per peptide strand. Overall, these results highlight the gain that can be achieved when the signal tranducing units of a biosensor are aligned through directed peptide chemistry.     

Activation of Toll-like receptor 4 is associated with insulin resistance in adipocytes

Chronic inflammation is closely associated with metabolic disorders such as obesity and type 2 diabetes, however, the underlying mechanism is unclear. Toll-like receptors (TLRs) play a key role in innate immune response as well as inflammatory signals. Here, we observed that mRNA level of TLR4 was induced during adipocyte differentiation and remarkably enhanced in fat tissues of obese db/db mice. In addition, activation of TLR4 with either LPS or free fatty acids stimulated NFkappaB signaling and expression of inflammatory cytokine genes, such as TNFalpha and IL-6 in 3T3-L1 adipocytes. Furthermore, we discovered that TLR4 activation in 3T3-L1 adipocytes provoked insulin resistance. Taken together, these results suggest that activation of TLR4 in adipocyte might be implicated in the onset of insulin resistance in obesity and type 2 diabetes.     

High-resolution structure of shikimate dehydrogenase from Thermotoga maritima reveals a tightly closed conformation

Shikimate dehydrogenase (SDH), which catalyses the NADPH-dependent reduction of 3-dehydroshikimate to shikimate in the shikimate pathway, is an attractive target for the development of herbicides and antimicrobial agents. Structural analysis of a SDH from Thermotoga maritima encoded by the Tm0346 gene was performed to facilitate further structural comparisons between the various shikimate dehydrogenases. The crystal structure of SDH from T. maritima was determined at 1.45 Å by molecular replacement. SDH from T. maritima showed a monomeric architecture. The overall structure of SDH from T. maritima comprises the N-terminal α/β sandwich domain for substrate binding and the C-terminal domain for NADP binding. When the T. maritima SDH structure was compared with those of the SDHs from other species, the SDH from T. maritima was in a tightly closed conformation, which should be open for catalysis. Notably, α7 moves toward the active site (∼5 Å), which forces the SDH of T. maritima in a more closed form. Four ammonium sulfate (AMS) ions were identified in the structure. They were located in the active site and appeared to mimic the role of the substrate in terms of the enzyme activity and stability. The new high resolution structural information reported in this study, including the AMS binding sites as a potent inhibitor binding site of SDHs, is expected to supplement the existing structural data and will be useful for structure-based antibacterial discovery against SDHs.     

Efficacy of β-mannanase supplementation to corn–soya bean meal-based diets on growth performance,nutrient digestibility,blood urea nitrogen,faecal coliform and lactic acid bacteria and faecal noxious gas emission in growing pigs

A study was conducted to determine the efficacy of β-mannanase supplementation to a diet based on corn and soya bean meal (SBM) on growth performance, nutrient digestibility, blood urea nitrogen (BUN), faecal coliforms and lactic acid bacteria, and noxious gas emission in growing pigs. A total of 140 pigs [(Landrace × Yorkshire) × Duroc; average body weight 25 ± 3 kg] were randomly allotted to a 2 × 2 factorial arrangement with dietary treatments consisting of hulled or dehulled SBM without or with supplementation of 400 U β-mannanase/kg. During the 6 weeks of experimental feeding, β-mannanase supplementation had no effect on body weight gain, feed intake and gain:feed (G:F) ratio. Compared with dehulled SBM, feeding hulled SBM caused an increased feed intake of pigs in the entire trial (p = 0.05). The G:F ratio was improved in pigs receiving dehulled SBM (p < 0.05). Dietary treatments did not influence the total tract digestibility of dry matter, nitrogen and gross energy. Enzyme supplementation reduced (p < 0.05) the population of faecal coliforms and tended to reduce the NH₃ concentration after 24 h of fermentation in a closed box containing faecal slurry. Feeding hulled SBM tended to reduce NH₃ emission on days 3 and 5 of fermentation. In conclusion, mannanase supplementation had no influence on growth performance and nutrient digestibility but showed a positive effect on reducing coliform population and tended to reduce NH₃ emission. Dehulled SBM increased G:F ratio and hulled SBM tended to reduce NH₃ emission.