Design,synthesis and biological evaluation of novel 2,3-indolinedione derivatives against mantle cell lymphoma

2,3-Indolinedione derivatives have been identified as a novel class of promising agents for cancer treatment. In this study, eighteen 2,3-indolinedione derivatives were designed and synthesized, and their anticancer activities against mantle cell lymphoma (MCL) cells were evaluated. Most of them exhibited significant antiproliferative activity against the tested cell lines, and compound K5 was the most potent (MCL cellular IC₅₀ = 0.4–0.7 μM). Further, compound K5 could induce cell apoptosis and cell cycle arrest in G2/M phase. Additionally, the results of drug-likeness analysis demonstrated that these novel 2,3-indolinedione derivatives could have potential as novel treatment strategies for MCL.     

Looking to the future: key points for sustainable management of northern Great Plains grasslands

The grasslands of the northern Great Plains (NGP) region of North America are considered endangered ecosystems and priority conservation areas yet have great ecological and economic importance. Grasslands in the NGP are no longer self‐regulating adaptive systems. The challenges to these grasslands are widespread and serious (e.g. climate change, invasive species, fragmentation, altered disturbance regimes, and anthropogenic chemical loads). Because the challenges facing the region are dynamic, complex, and persistent, a paradigm shift in how we approach restoration and management of the grasslands in the NGP is imperative. The goal of this article is to highlight four key points for land managers and restoration practitioners to consider when planning management or restoration actions. First, we discuss the appropriateness of using historical fidelity as a restoration or management target because of changing climate, widespread pervasiveness of invasive species, the high level of fragmentation, and altered disturbance regimes. Second, we highlight ecosystem resilience and long‐term population persistence as alternative targets. Third, because the NGP is so heavily impacted with anthropogenic chemical loading, we discuss the risks of ecological traps and extinction debt. Finally, we highlight the importance of using adaptive management and having patience during restoration and management. Consideration of these four points will help management and restoration of grasslands move toward a more successful and sustainable future. Although we specifically focus on the NGP of North America, these same issues and considerations apply to grasslands and many other ecosystems globally.     

Microplastic ingestion ubiquitous in marine turtles

Despite concerns regarding the environmental impacts of microplastics, knowledge of the incidence and levels of synthetic particles in large marine vertebrates is lacking. Here, we utilize an optimized enzymatic digestion methodology, previously developed for zooplankton, to explore whether synthetic particles could be isolated from marine turtle ingesta. We report the presence of synthetic particles in every turtle subjected to investigation (n = 102) which included individuals from all seven species of marine turtle, sampled from three ocean basins (Atlantic [ATL]: n = 30, four species; Mediterranean (MED): n = 56, two species; Pacific (PAC): n = 16, five species). Most particles (n = 811) were fibres (ATL: 77.1% MED: 85.3% PAC: 64.8%) with blue and black being the dominant colours. In lesser quantities were fragments (ATL: 22.9%: MED: 14.7% PAC: 20.2%) and microbeads (4.8%; PAC only; to our knowledge the first isolation of microbeads from marine megavertebrates). Fourier transform infrared spectroscopy (FT‐IR) of a subsample of particles (n = 169) showed a range of synthetic materials such as elastomers (MED: 61.2%; PAC: 3.4%), thermoplastics (ATL: 36.8%: MED: 20.7% PAC: 27.7%) and synthetic regenerated cellulosic fibres (SRCF; ATL: 63.2%: MED: 5.8% PAC: 68.9%). Synthetic particles being isolated from species occupying different trophic levels suggest the possibility of multiple ingestion pathways. These include exposure from polluted seawater and sediments and/or additional trophic transfer from contaminated prey/forage items. We assess the likelihood that microplastic ingestion presents a significant conservation problem at current levels compared to other anthropogenic threats.     

Stress and disturbance determine the demographic dynamics of two grass species along a grazing gradient in Southern Mexico

Chronic anthropogenic disturbance (CAD), characterized by low-intensity but high frequency, is a major driver of environmental degradation in developing countries. CAD is a mixture of disturbance sensu stricto (DSS), that is, plant biomass removal and stress that reduces biomass production due to changes in environmental conditions. However, we still lack data on the separate effects of both components and their interaction in nature. We analyze the demographic effects of DSS and stress on two grass species in an area heavily affected by livestock raising (a widespread cause of CAD) during the last 500 year. We compared areas exposed to DSS and stress with areas without grazing but that continue experiencing a gradient of stress. Using matrix and integral projection models, we analyzed DSS and stress effects on population growth rates (λ) of two grass species and determined the relative importance of different vital rates and states for the change on λ. Disturbance and stress affected different individuals and processes. For example, changed conditions due to stress increased seedling mortality, but DSS reduced size (growth) of large plants through grazing. CAD had highly nonlinear and species-specific effects on population size structures, λ and elasticities. Such complex behavior is seemingly due to changes in the components of CAD as it intensified and synergic interactions between disturbance and stress. Given CAD's multivariate nature, these results are not surprising. Nevertheless, grouping this multitude of factors into two broad categories, namely DSS and stress, may prove a useful conceptual tool for analysis.     

天然间苯三酚的化学结构和药理活性研究进展

天然的间苯三酚类化合物来源广泛、结构新颖,具有多种药理活性,是目前天然药物化学的研究热点之一。本文对近十年发现的天然间苯三酚类化合物的化学结构和药理活性的研究进展做了调研和综述,以期对该类化合物进一步的研究提供参考。     

疏勒河流域气候变化和人类活动对植被NPP的相对影响评价

气候变化和人类活动是对陆地生态系统碳循环产生重要影响的两个因素,定量评估气候变化与人类活动对植被净初级生产力(NPP)的相对影响,对深入理解其驱动机制和控制荒漠化发展具有重要意义。以疏勒河流域为研究区,利用遥感和气象数据计算潜在NPP(PNPP)及其与实际NPP(ANPP)之间的差值,分别衡量了气候变化和人类活动对流域NPP的相对影响。研究结果表明:(1)2001—2015年疏勒河流域年ANPP整体呈缓慢增加趋势,与全国和西北地区相比,普遍较低,流域植被整体生产力水平不高。流域年ANPP空间分布呈现上游祁连山区和中下游绿洲区ANPP较高,而中下游荒漠戈壁区ANPP较低的分布格局。(2)2001—2015年流域年PNPP的变化趋势表明,降水量的变化是导致疏勒河流域植被退化加剧或缓解的主要气候驱动因素,但气温的变化对植被的影响较为复杂。(3)2001—2015年流域大部分地区植被退化系人类活动造成的,但人类活动的负向影响力在减弱。(4)气候变化和人类活动对植被NPP的相对影响均表现出明显的空间异质性,其中人类活动是疏勒河流域植被变化的主要驱动因素。     

Phenolic derivatives with cytotoxic activities from the roots of Fallopia multiflora var. ciliinervis

Fourteen phenolic derivatives including two new compounds (1, 2), one new natural product (10) and eleven known ones (3 - 9 and 11–14) were obtained from the roots of Fallopia multiflora var. ciliinervis. The structures were determined using IR, MS, 1D and ²D NMR spectroscopy and the absolute configuration of the new structure (2) was deduced by ECD experiments. All of the isolated compounds were assayed for their cytotoxic activities against three tumor cell lines (A549, HCT116 and SW620) and the results showed that compounds 12－14 showed cytotoxicities against A549 cells while compounds 10 and 11 showed cytotoxicities against SW620 cells.     

Cellular functions of NSF: not just SNAPs and SNAREs

N-ethylmaleimide sensitive factor (NSF) is an ATPases associated with various cellular activities protein (AAA), broadly required for intracellular membrane fusion. NSF functions as a SNAP receptor (SNARE) chaperone which binds, through soluble NSF attachment proteins (SNAPs), to SNARE complexes and utilizes the energy of ATP hydrolysis to disassemble them thus facilitating SNARE recycling. While this is a major function of NSF, it does seem to interact with other proteins, such as the AMPA receptor subunit, GluR2, and beta2-AR and is thought to affect their trafficking patterns. New data suggest that NSF may be regulated by transient post-translational modifications such as phosphorylation and nitrosylation. These new aspects of NSF function as well as its role in SNARE complex dynamics will be discussed.     

Kinetics of the Anti-oxidant Response to Salinity in the Halophyte Cakile maritima

The effects of NaCl stress on the activity of anti-oxidant enzymes （superoxide dismutase, catalase （CAT）, peroxidase （POD）, ascorbate peroxidase （APX）, monodehydroascorbate reductase, dehydroascorbate reductase （DHAR）, and glutathione reductase （GR））, anti-oxidant molecules （ascorbate and glutathione）, and parameters of oxidative stress （malondialdehyde （MDA）, electrolyte leakage, and H2O2 concentrations） were investigated in Cakile maritima, a halophyte frequent along the Tunisian seashore. Seedlings were grown in the presence of salt （100, 200, and 400 mmol/L NaCl）. Plants were harvested periodically over 20 days. Growth was maximal in the presence of 0-100 mmol/L NaCl. At 400 mmol/L NaCl, growth decreased significantly. The salt tolerance of C. maritima, at moderate salinities, was associated with the lowest values of the parameters indicative of oxidative stress, namely the highest activities of POD, CAT, APX, DHAR, and GR and high tissue content of ascorbate and glutathione. However, prolonged exposure to high salinity resulted in a decrease in anti-oxidant activities and high MDA content, electrolyte leakage, and H2O2 concentrations. These results suggest that anti-oxidant systems participate in the tolerance of C. maritima to moderate salinities.