Scale‐down simulators for mammalian cell culture as tools to access the impact of inhomogeneities occurring in large‐scale bioreactors

During the scale‐up of a bioprocess, not all characteristics of the process can be kept constant throughout the different scales. This typically results in increased mixing times with increasing reactor volumes. The poor mixing leads in turn to the formation of concentration gradients throughout the reactor and exposes cells to varying external conditions based on their location in the bioreactor. This can affect process performance and complicate process scale‐up. Scale‐down simulators, which aim at replicating the large‐scale environment, expose the cells to changing environmental conditions. This has the potential to reveal adaptation mechanisms, which cells are using to adjust to rapidly fluctuating environmental conditions and can identify possible root causes for difficulties maintaining similar process performance at different scales. This understanding is of utmost importance in process validation. Additionally, these simulators also have the potential to be used for selecting cells, which are most robust when encountering changing extracellular conditions. The aim of this review is to summarize recent work in this interesting and promising area with the focus on mammalian bioprocesses, since microbial processes have been extensively reviewed.     

Development,characterization, and application of a 2‐Compartment system to investigate the impact of pH inhomogeneities in large‐scale CHO‐based processes

Large‐scale bioreactors for the production of monoclonal antibodies reach volumes of up to 25 000 L. With increasing bioreactor size, mixing is however affected negatively, resulting in the formation of gradients throughout the reactor. These gradients can adversely affect process performance at large scale. Since mammalian cells are sensitive to changes in pH, this study investigated the effects of pH gradients on process performance. A 2‐Compartment System was established for this purpose to expose only a fraction of the cell population to pH excursions and thereby mimicking a large‐scale bioreactor. Cells were exposed to repeated pH amplitudes of 0.4 units (pH 7.3), which resulted in decreased viable cell counts, as well as the inhibition of the lactate metabolic shift. These effects were furthermore accompanied by increased absolute lactate levels. Continuous assessment of molecular attributes of the expressed target protein revealed that subunit assembly or N‐glycosylation patterns were only slightly influenced by the pH excursions. The exposure of more cells to the same pH amplitudes further impaired process performance, indicating this is an important factor, which influences the impact of pH inhomogeneity. This knowledge can aid in the design of pH control strategies to minimize the effects of pH inhomogeneity in large‐scale bioreactors.     

基于景观地形的小流域单元减灾调控评价研究

近年来,中国诸多大中城市内涝灾害频发。武汉市作为城市内涝频发的典型城市,其建成区地表高度（20.0~24.0 m）大多低于外江常年所处的洪水位高度（23.9 m）,在区域性暴雨条件下,极易引发内涝灾害。武汉由于其内涝典型性,2013年被列为全国31个重点防洪城市之一,2015年被列入首批海绵城市试点城市之一。从城市内涝发生机理出发,以水文角度的小流域单元作为内涝风险区划的基本单元,利用小流域单元分析武汉市景观地形要素（地表高程、地表起伏度、地表粗糙度）与城市内涝积水密度的相关性及其影响程度,量算统计出小流域单元的内涝风险等级。基于此,提出武汉市小流域单元减灾地形调控评价。以武汉市作为城市内涝问题的研究案例,以期为武汉市内涝缓解提供新的思考路径,具有典型性和必要性。     

Membrane‐Free Zn/MnO2 Flow Battery for Large‐Scale Energy Storage

The traditional Zn/MnO₂ battery has attracted great interest due to its low cost, high safety, high output voltage, and environmental friendliness. However, it remains a big challenge to achieve long‐term stability, mainly owing to the poor reversibility of the cathode reaction. Different from previous studies where the cathode redox reaction of MnO₂/MnOOH is in solid state with limited reversibility, here a new aqueous rechargeable Zn/MnO₂ flow battery is constructed with dissolution–precipitation reactions in both cathodes (Mn²⁺/MnO₂) and anodes (Zn²⁺/Zn), which allow mixing of anolyte and catholyte into only one electrolyte and remove the requirement for an ion selective membrane for cost reduction. Impressively, this new battery exhibits a high discharge voltage of ≈1.78 V, good rate capability (10C discharge), and excellent cycling stability (1000 cycles without decay) at the areal capacity ranging from 0.5 to 2 mAh cm^‐2. More importantly, this battery can be readily enlarged to a bench scale flow cell of 1.2 Ah with good capacity retention of 89.7% at the 500th cycle, displaying great potential for large‐scale energy storage.     

Continuous Flow Routes toward Designer Metal Nanocatalysts

Mono‐ and multimetallic nanoparticles (NPs) have diverse and tunable physicochemical properties that arise from their compositions as well as crystallite size and shape. The ability to control precisely the composition and structure of NPs through synthesis is central to achieving state‐of‐the‐art designer metal NPs for use as catalysts and electrocatalysts. However, a major limitation to the use of designer metal NPs as catalysts is the ability to scale their syntheses while maintaining structural precision. To address this challenge, continuous flow routes to metal NPs involving the use of droplet microreactors are being developed, providing the synthetic versatility necessary to achieve known and completely new nanostructures. This progress report outlines how the chemistry and process parameters of droplet microreactors can be used to achieve high performing nanocatalysts through control of NP composition, size, shape, and architecture and outlines directions toward previously unimaginable nanostructures.     

腔隙性脑梗死伴脑白质病变患者血清miR-146a和NSE水平与MoCA评分的关系研究

摘要 目的：研究腔隙性脑梗死（LI）伴脑白质病变（WML）患者血清miR-146a和神经元特异性烯纯化酶（NSE）水平与蒙特利尔认知评估量表（MoCA）评分的关系。方法：纳入我院从2017年3月～2019年3月收治的LI伴WML患者108例进行研究,记作LI伴WML组。另取同期收治的单纯WML患者与单纯LI患者各100例,分别记作WML组与LI组,再取同期于我院进行体检的健康人员100例作为对照组。比较四组人员的血清miR-146a和NSE水平、MoCA评分,并作相关性分析。结果：LI伴WML组、WML组、LI组血清miR-146a相对表达量均低于对照组,而LI伴WML组血清miR-146a相对表达量又显著低于WML组、LI组（均P＜0.05）;LI伴WML组、WML组、LI组血清NSE水平均显著高于对照组,且LI伴WML组血清NSE水平均显著高于WML组、LI组（均P＜0.05）。LI伴WML组MoCA总分显著低于WML组与LI组,且WML组与LI组MoCA总分显著低于对照组（均P＜0.05）。经Pearson相关性分析可得：LI伴WML组患者血清miR-146a相对表达量与MoCA总分呈正相关关系（P＜0.05）,而血清NSE水平与MoCA总分呈负相关关系（P＜0.05）。结论：LI伴WML患者的血清miR-146a水平存在明显低表达,而NSE水平存在明显高表达,并与MoCA评分相关,两者可能在认知功能损伤的发生、发展过程中起着至关重要的作用。     

滇川桂3省暗褐网柄牛肝菌菌腔虫瘿的寄主植物与介壳虫种类调查

暗褐网柄牛肝菌Phlebopus portentosus与介壳虫形成的菌腔虫瘿是该菌营养机制研究的关键环节。本研究先后在云南、四川和广西3省区暗褐网柄牛肝菌产区的16个地点,对菌腔虫瘿的生态和生物学进行了大量的野外调查。发现根部着生菌腔虫瘿的寄主植物有31种,涉及16个科的28个属。与暗褐网柄牛肝菌形成菌腔虫瘿的介壳虫种类有12种,其中10种隶属粉蚧科Pseudococcidae、绵蚧科Monophlebidae、蚧科Coccidae各1种。在不同的寄主植物上菌腔虫瘿的寄生位置和形状会有所不同,与暗褐网柄牛肝菌菌丝形成菌腔虫瘿的寄主植物和介壳虫之间不存在专一性。上述研究结果为暗褐网柄牛肝菌的仿生栽培奠定了基础。     

Leaf size of woody dicots predicts ecosystem primary productivity

A key challenge in ecology is to understand the relationships between organismal traits and ecosystem processes. Here, with a novel dataset of leaf length and width for 10 480 woody dicots in China and 2374 in North America, we show that the variation in community mean leaf size is highly correlated with the variation in climate and ecosystem primary productivity, independent of plant life form. These relationships likely reflect how natural selection modifies leaf size across varying climates in conjunction with how climate influences canopy total leaf area. We find that the leaf size?primary productivity functions based on the Chinese dataset can predict productivity in North America and vice‐versa. In addition to advancing understanding of the relationship between a climate‐driven trait and ecosystem functioning, our findings suggest that leaf size can also be a promising tool in palaeoecology for scaling from fossil leaves to palaeo‐primary productivity of woody ecosystems.     

Comparing urban food system characteristics and actions in US and Indian cities from a multi‐environmental impact perspective: Toward a streamlined approach

Food action plans in many global cities articulate interest in multiple objectives including reducing in‐ and trans‐boundary environmental impacts (water, land, greenhouse gas (GHG)). However, there exist few standardized analytical tools to compare food system characteristics and actions across cities and countries to assess trade‐offs between multiple objectives (i.e., health, equity) with environmental outcomes. This paper demonstrates a streamlined model applied for analysis of four cities with varying characteristics across the United States and India, to quantify system‐wide water, energy/GHG, and land impacts associated with multiple food system actions to address health, equity, and environment. Baseline diet analysis finds key differences between countries in terms of meat consumption (Delhi 4; Pondicherry 16; United States 59, kg/capita/year), and environmental impact of processing of the average diet (21%, 19%, <1%, <1% of community‐wide GHG‐emissions for New York, Minneapolis, Delhi, and Pondicherry). Analysis of supply chains finds city average distance (food‐miles) varies (Delhi 420; Pondicherry 200; United States average 1,640 km/t‐food) and the sensitivity of GHG emissions of food demand to spatial variability of energy intensity of irrigation is greater in Indian than US cities. Analysis also finds greater pre‐consumer waste in India versus larger post‐consumer accumulations in the United States. Despite these differences in food system characteristics, food waste management and diet change consistently emerge as key strategies. Among diet scenarios, all vegetarian diets are not found equal in terms of environmental benefit, with the US Government's recommended vegetarian diet resulting in less benefit than other more focused targeted diet changes.