具有保肝作用的天然药物开发进展

肝脏是机体代谢的最主要场所,也是机体最容易遭受到损伤的脏器之一,各种因素引起的肝损伤已成为威胁人类健康的重要疾病之一。肝损伤机制主要与线粒体损伤、自由基脂质过氧化、炎症细胞因子分泌和细胞膜损伤有关。目前已报道很多天然药物具有显著保肝作用,且具有疗效稳定、副作用低、多途径作用、作用温和持久等优势,已广泛用于肝脏疾病的防治。本文对肝损伤的生理机制以及具有保肝作用的天然药物开发进展进行了综述,提出了目前存在的一些问题并进行了展望。     

Fluctuating selection and its (elusive) evolutionary consequences in a wild rodent population

Temporal fluctuations in the strength and direction of selection are often proposed as a mechanism that slows down evolution, both over geological and contemporary timescales. Both the prevalence of fluctuating selection and its relevance for evolutionary dynamics remain poorly understood however, especially on contemporary timescales: unbiased empirical estimates of variation in selection are scarce, and the question of how much of the variation in selection translates into variation in genetic change has largely been ignored. Using long‐term individual‐based data for a wild rodent population, we quantify the magnitude of fluctuating selection on body size. Subsequently, we estimate the evolutionary dynamics of size and test for a link between fluctuating selection and evolution. We show that, over the past 11 years, phenotypic selection on body size has fluctuated significantly. However, the strength and direction of genetic change have remained largely constant over the study period; that is, the rate of genetic change was similar in years where selection favoured heavier vs. lighter individuals. This result suggests that over shorter timescales, fluctuating selection does not necessarily translate into fluctuating evolution. Importantly however, individual‐based simulations show that the correlation between fluctuating selection and fluctuating evolution can be obscured by the effect of drift, and that substantially more data are required for a precise and accurate estimate of this correlation. We identify new challenges in measuring the coupling between selection and evolution, and provide methods and guidelines to overcome them.     

Choice of Allocations and Constructs for Attributional or Consequential Life Cycle Assessment and Input‐Output Analysis

The divide between attributional and consequential research perspectives partly overlaps with the long‐standing methodological discussions in the life cycle assessment (LCA) and input‐output analysis (IO) research communities on the choice of techniques and models for dealing with situations of coproduction. The recent harmonization of LCA allocations and IO constructs revealed a more diverse set of coproduction models than had previously been understood. This increased flexibility and transparency in inventory modeling warrants a re‐evaluation of the treatment of coproduction in analyses with attributional and consequential perspectives. In the present article, the main types of coproductions situations and of coproduction models are reviewed, along with key desirable characteristics of attributional and consequential studies. A concordance analysis leads to clear recommendations, which call for important refinements to current guidelines for both LCA/IO practitioners and database developers. We notably challenge the simple association between, on the one hand, attributional LCA and partition allocation, and on the one hand, consequential LCA and substitution modeling.     

A journey through time: exploring temporal patterns amongst digitized plant specimens from Australia

Online access to species occurrence records has opened new windows into investigating biodiversity patterns across multiple scales. The value of these records for research depends on their spatial, temporal, and taxonomic quality. We assessed temporal patterns in records from the Australasian Virtual Herbarium, asking: (1) How temporally consistent has collecting been across Australia? (2) Which areas of Australia have the most reliable records, in terms of temporal consistency and inventory completeness? (3) Are there temporal trends in the completeness of attribute information associated with records? We undertook a multi-step filtering procedure, then estimated temporal consistency and inventory completeness for sampling units (SUs) of 50?km ×?50?km. We found temporal bias in collecting, with 80% of records collected over the period 1970–1999. South-eastern Australia, the Wet Tropics in north-east Queensland, and parts of Western Australia have received the most consistent sampling effort over time, whereas much of central Australia has had low temporal consistency. Of the SUs, 18% have relatively complete inventories with high temporal consistency in sampling. We also determined that 25% of digitized records had missing attribute information. By identifying areas with low reliability, we can limit erroneous inferences about distribution patterns and identify priority areas for future sampling.     

The natural agent rhein induces β‐catenin degradation and tumour growth arrest

The natural agent rhein is an ananthraquinone derivative of rhubarb, which has anticancer effects. To determine the mechanisms underlying the anticancer effects of rhein, we detected the effect of rhein on several oncoproteins. Here, we show that rhein induces β‐catenin degradation in both hepatoma cell HepG2 and cervical cancer cell Hela. Treatment of HepG2 and Hela cells with rhein shortens the half‐life of β‐catenin. The proteasome inhibitor MG132 blunts the downregulation of β‐catenin by rhein. The induction of β‐catenin degradation by rhein is dependent on GSK3 but independent of Akt. Treatment of HepG2 and Hela cells with GSK3 inhibitor or GSK3β knockdown abrogates the effect of rhein on β‐catenin. GSK3β knockdown compromises the inhibition of HepG2 and Hela cell growth by rhein. Furthermore, rhein dose not downregulate β‐catenin mutant that is deficient of phosphorylation at multiple residues including Ser33, Ser37, Thr41 and Ser45. Moreover, rhein induces cell cycle arrest at S phase in both HepG2 and Hela cells. Intraperitoneal administration of rhein suppresses tumour cells proliferation and tumour growth in HepG2 xenografts model. Finally, the levels of β‐catenin are reduced in rhein‐treated tumours. These data demonstrate that rhein can induce β‐catenin degradation and inhibit tumour growth.     

海洋微生物学：新机遇，新挑战

海洋占地球表面积的71%,海洋微生物对海洋及人类的生活有重大影响。由于特殊的生存环境,海洋微生物能产生陆栖微生物所不能产生的结构新颖、作用特殊的生物活性物质,有潜力应用于医疗、食品、环境保护等各个领域。海洋微生物研究充满了新的机遇,同时也面临着新的挑战。《微生物学通报》本期推出了"海洋微生物学主题刊",旨在展现我国海洋微生物学研究的最新进展和成果,促进我国海洋微生物学的交流和发展。     

Virtual target screening reveals rosmarinic acid and salvianolic acid A inhibiting metallo- and serine-β-lactamases

Rosmarinic acid (RA), a polyphenolic phytochemical, has broad-spectrum biological and pharmacological activity. A virtual target screening method termed IFPTarget combined with enzyme inhibition assays led to the identification of the clinically relevant metallo-β-lactamase (MBL) VIM-2 as one of unexploited targets of RA. The enzyme kinetic studies indicated that RA is a fully reversible, substrate-competitive VIM-2 inhibitor. The isothermal titration calorimetry (ITC) analyses revealed that the initial binding of RA to VIM-2 is mainly due to enthalpy contribution. Further inhibition assays with RA related compounds revealed that salvianolic acid A, a derivative of RA, manifests potent inhibition to VIM-2, more interestingly, which shows inhibitory activity against the NDM-1, another clinically relevant MBL subtype, and the serine-β-lactamase TEM-1 that is structurally and mechanistically distinct from the VIM-2 and NDM-1.     

Kakeromamide A,a new cyclic pentapeptide inducing astrocyte differentiation isolated from the marine cyanobacterium Moorea bouillonii

Kakeromamide A (1), a new cyclic pentapeptide encompassing a thiazole ring moiety and a β-amino acid, was isolated from the marine cyanobacterium Moorea bouillonii. Its structure was elucidated by the spectral analysis and the modified Marfey’s method. Compound 1 induced differentiation of neural stem cells into astrocytes at the concentration of 10?µM.