Axelle Cooreman  Anne Caufriez  Andrs Tabernilla  Raf Van Campenhout  Kaat Leroy  Prashant Kadam  Julen Sanz Serrano  Bruna dos Santos Rodrigues  Pieter Annaert  Mathieu Vinken 《International journal of molecular sciences》2022,23(9)

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Audrey M. Neyrinck  Julie Rodriguez  Bernard Taminiau  Florent Herpin  Patrice D. Cani  Georges Daube  Laure B. Bindels  Nathalie M. Delzenne 《International journal of molecular sciences》2022,23(23)

Gut microbiota alterations are intimately linked to chronic constipation upon aging. We investigated the role of targeted changes in the gut microbiota composition in the relief of constipation symptoms after rhubarb extract (RE) supplementation in middle-aged volunteers. Subjects (95% women, average 58 years old) were randomized to three groups treated with RE at two different doses determined by its content of rhein (supplementation of 12.5 mg and 25 mg per day) vs. placebo (maltodextrin) for 30 days. We demonstrated that daily oral supplementation of RE for 30 days was safe even at the higher dose. Stool frequency and consistency, and perceived change in transit problem, transit speed and difficulty in evacuating, investigated by validated questionnaires, were improved in both groups of RE-treated volunteers compared to placebo. Higher abundance of Lachnospiraceae (mainly Roseburia and Agathobacter) only occurred after RE treatment when present at low levels at baseline, whereas an opposite shift in short-chain fatty acid (SCFA) levels was observed in both RE-treated groups (increase) and placebo (decrease). Fecal Lachnospiraceae and SCFA were positively correlated with stool consistency. This study demonstrates that RE supplementation promotes butyrate-producing bacteria and SCFA, an effect that could contribute to relieving chronic constipation in middle-aged persons.  相似文献   

    

Roberta J. Ward  David T. Dexter  Robert R. Crichton 《International journal of molecular sciences》2022,23(13)

Disturbance of the brain homeostasis, either directly via the formation of abnormal proteins or cerebral hypo-perfusion, or indirectly via peripheral inflammation, will activate microglia to synthesise a variety of pro-inflammatory agents which may lead to inflammation and cell death. The pro-inflammatory cytokines will induce changes in the iron proteins responsible for maintaining iron homeostasis, such that increased amounts of iron will be deposited in cells in the brain. The generation of reactive oxygen and nitrogen species, which is directly involved in the inflammatory process, can significantly affect iron metabolism via their interaction with iron-regulatory proteins (IRPs). This underlies the importance of ensuring that iron is maintained in a form that can be kept under control; hence, the elegant mechanisms which have become increasingly well understood for regulating iron homeostasis. Therapeutic approaches to minimise the toxicity of iron include N-acetyl cysteine, non-steroidal anti-inflammatory compounds and iron chelation.  相似文献   

    

Jolien Beeken  Sofie Kessels  Jean-Michel Rigo  Yeranddy A. Alpizar  Laurent Nguyen  Bert Brne 《International journal of molecular sciences》2022,23(18)

p27^kip1 is a multifunctional protein that promotes cell cycle exit by blocking the activity of cyclin/cyclin-dependent kinase complexes as well as migration and motility via signaling pathways that converge on the actin and microtubule cytoskeleton. Despite the broad characterization of p27^kip1 function in neural cells, little is known about its relevance in microglia. Here, we studied the role of p27^kip1 in microglia using a combination of in vitro and in situ approaches. While the loss of p27^kip1 did not affect microglial density in the cerebral cortex, it altered their morphological complexity in situ. However, despite the presence of p27^kip1 in microglial processes, as shown by immunofluorescence in cultured cells, loss of p27^kip1 did not change microglial process motility and extension after applying laser-induced brain damage in cortical brain slices. Primary microglia lacking p27^kip1 showed increased phagocytic uptake of synaptosomes, while a cell cycle dead variant negatively affected phagocytosis. These findings indicate that p27^kip1 plays specific roles in microglia.  相似文献   

    

Nitesh K. Gupta  Srinivasan Jayakumar  Wen-Chieh Huang  Pieter Leyssen  Johan Neyts  Sergey O. Bachurin  Jih Ru Hwu  Shwu-Chen Tsay 《International journal of molecular sciences》2022,23(20)

The yellow fever virus (YFV) is an emerging RNA virus and has caused large outbreaks in Africa and Central and South America. The virus is often transmitted through infected mosquitoes and spreads from area to area because of international travel. Being an acute viral hemorrhagic disease, yellow fever can be prevented by an effective, safe, and reliable vaccine, but not be eliminated. Currently, there is no antiviral drug available for its cure. Thus, two series of novel bis(benzofuran–1,3-imidazolidin-4-one)s and bis(benzofuran–1,3-benzimidazole)s were designed and synthesized for the development of anti-YFV lead candidates. Among 23 new bis-conjugated compounds, 4 of them inhibited YFV strain 17D (Stamaril) on Huh-7 cells in the cytopathic effect reduction assays. These conjugates exhibited the most compelling efficacy and selectivity with an EC₅₀ of <3.54 μM and SI of >15.3. The results are valuable for the development of novel antiviral drug leads against emerging diseases.  相似文献   

    

《CIRP Annals》2022,71(1):257-260

Due to their enhanced mechanical and magnetic properties, composite wire bundles play a central role in many industrial areas. For the production of these parts, continuous metal forming processes with stationary conditions are economically advantageous and enable large-scale production. However, the different mechanical properties of the materials used in the composite rods often make a continuous process execution a technological challenge. The paper at hand investigates the process limits of swaging operations of wire bundles via analytical, numerical and experimental methods. The knowledge gained about the effect of process parameters on the material flow enables a favourable process design.  相似文献   

    

《CIRP Annals》2022,71(1):121-124

Automating design faces a thorny problem: insight modeling based on knowledge and experience. In particular, it is difficult for artificial intelligence to perform incomplete conditional reasoning. The deep generative model (DGM) is an emerging approach of machine learning, which typically uses deep networks to learn from various data sets and synthesize new designs. This paper proposes a novel DGM based on imaginal thinking to realize the creative leap from the invisible functional domain to the concrete physical domain. An experiment is conducted to verify the effectiveness of the proposed model in designing wheels for mobile robots in granular media.  相似文献   

    

《CIRP Annals》2022,71(2):717-739

This paper takes the broad topic of geometrical surface imperfections on manufactured surfaces and provides an overview of how they affect component functionality and how they may be detected and classified as defects or not. The presented overview considers both human visual inspection and machine vision-based approaches along with their evolving roles. Of note is that the paper takes a highly granular field consisting of customized solutions for customized applications and frames the discussion around fundamental considerations for each of the tasks; search/acquisition, sensing/detection, processing, classification and decision. Future trends and areas still requiring attention are highlighted.  相似文献   

    

《CIRP Annals》2022,71(2):623-646

Because of their many applications, including automotive, aeronautics, optics, and so forth, demand for grinding tools sees unabated growth. But the energy and resource intensive nature of their manufacture leads to questions of sustainability. This paper details how recent developments in basic tool technology (structure, binder, abrasives) is increasing tool and abrasive resilience while reducing production inputs. The advent of smart grinding tools involving aspects of surface engineering, process hybridization, and process monitoring is also discussed. The paper concludes with an outlook of further energy savings, tool recycling and uses of additive manufacturing with the aim of achieving long-term sustainability.  相似文献   

    

《CIRP Annals》2022,71(2):647-670

Machine tools involve various mechanical interfaces in different forms and styles, which affect performance significantly in terms of rigidity, thermal stability, precision, and accuracy. This paper reviews the state-of-the-art and future trends in machine tool structural interfaces. The main concepts, challenges, and improvements regarding mechanical and thermal characteristics, geometric accuracy and precision, and wear and failure of machine tool interfaces are presented. Advanced methods for modeling static, dynamic, thermal, and geometrical behavior of mechanical interfaces are presented with examples. Furthermore, typical wear and failure mechanisms and available solutions and health monitoring techniques are covered.  相似文献