312 research outputs found
Hollowing out MOFs: hierarchical micro- and mesoporous MOFs with tailorable porosity via selective acid etching
No full textWe report a new strategy for the synthesis of robust hierarchical micro- and mesoporous MOFs from water stable MOFs via a selective acid etching process. The process is controlled by the size-selective diffusion of acid molecules through the MOF windows. This method enables the fine-tuning of the porosity of hierarchical MOFs, allowing for the generation of well-defined mesopores with high mesopore volume. Because of the size-selective diffusion of acid molecules, the inherent crystallinity and external morphology of the resulting MOFs are well-maintained after acid treatment. This novel strategy may provide an alternative route towards the synthesis of diverse hierarchical MOFs.1115Ysciescopu
The Salmonella SPI-2 Type III secretion system: regulation of a substrate specificity switch and functional analysis of the SpvD effector
No full textOne of the main determinants enabling Salmonella enterica serovar Typhimurium to replicate inside host cells is a type III secretion system (T3SS; an injectisome) encoded by Salmonella pathogenicity island 2 (SPI-2). This multi-protein structure assembles upon acidification of a Salmonella-containing vacuole (SCV) that surrounds Salmonella following host cell entry. It functions as a conduit that connects the bacterium to the host cytosol and translocates so called “SPI-2 effector” proteins that manipulate the host to support bacterial growth. The delivery of these proteins is spatiotemporally controlled by a gatekeeper complex composed of SsaL/SsaM/SpiC proteins (Yu et al., 2010). The gatekeeper prevents effector protein translocation, but is required for the export of translocon proteins that enable effectors to cross the vacuolar membrane into the cell. The SPI-2 effector proteins are translocated to the host cell only when the gatekeeper dissociates away from the injectisome, a process initiated by sensing a low-to-neutral pH shift (Yu et al., 2010). The functions of the SPI-2 injectisome and gatekeeper can be studied by growth of Salmonella at low pH medium followed by a shift to pH 7.2 (Beuzón et al., 1999; Yu et al., 2010). In a detailed alanine scanning mutagenesis of SsaL it was demonstrated that several amino acid positions, mainly located at the C-terminal domain of SsaL, are critical for the gatekeeper function when tested in an in vitro secretion assay. One mode of action of the gatekeeper could rely on a specific interaction with the translocon proteins that enables their subsequent secretion. Interactions between SsaL and the translocon proteins SseB and SseC were detected, however their exact manner requires further investigation.
In a second part of this work, I focused on biochemical analysis of SpvD, an anti-inflammatory effector protein of unknown function encoded by the spv operon within pSLT virulence plasmid (Rolhion et al., in preparation). During this study it was determined that SpvD acts in vitro as a protease and that this activity depends on cysteine C73. A crystal structure determined as a result of collaboration with Dr Stephen Hare clearly shows that SpvD adopts a papain-like fold with a C73/H162/D182 catalytic triad, a characteristic feature and key element required for the enzymatic activities of this superfamily of proteins. A detailed analysis of the protein structure revealed a putative inhibitory arginine R161 that might obstruct the activity of SpvD. A subsequent BLAST search of SpvD amino acid sequences demonstrated serovar-specific differences at position 161. Mutations of the Typhimurium SpvD variant that mimicked SpvD from other serovars increased the proteolytic activity in an in vitro cleavage assay. Whether this polymorphism reflects host adaptation or partial loss of activity requires further investigation, as does identification of the physiological substrate(s) of SpvD.Open Acces
Dramatically Enhanced Reactivity of Fullerenes and Tetrazine towards the Inverse-Electron-Demand Diels-Alder Reaction inside a Porous Porphyrinic Cage
No full textInverse-electron-demand Diels-Alder reaction (IEDDA) between fullerenes and 1,2,4,5-tetrazine generally requires harsh conditions and long reaction times due to their strong electron-accepting nature. Herein, we report a dramatic enhancement in the reactivity of the fullerenes (C-60/C-70)-tetrazine reaction inside a porous Zn-porphyrinic cage (Zn-PB) under sustainable conditions by installing a tetrazine-based axle (LA) via metal-ligand coordination bond, which modulates the cavity size to facilitate the encapsulation of fullerenes. Upon encapsulation, the close proximity of fullerenes and the tetrazine group of LA dramatically increase their reactivity towards the IEDDA reaction to form fullerene-tetrazine adducts. Furthermore, the C-60-tetrazine adduct is rearranged upon hydration to a bent-shaped C-60-pyrazoline adduct that can be released from the Zn-PB cavity in the presence of excess LA, thus catalyzing the formation of C-60-pyrazoline adduct inside Zn-PB without product inhibition.11Nsciescopu
Microfluidic devices for developing tissue scaffolds
No full textThis chapter begins by outlining the key hurdles that currently exist in terms of achieving directed tissue genesis, in vitro and in vivo, from available mature, progenitor and stem cell sources. The chapter then Sugiura et al., 2005 proceeds to describe how microfluidic device platforms can provide the required insights to overcome these hurdles to clinical translation, including the optimization of soluble factor provision to enhance cell expansion and differentiation outcomes, the impacts of pore architecture and surface engineering on scaffold colonization, and the biophysical needs of cells when creating three dimensional artificial vascular pedicles for improved scaffold vascularization post-implantation
Microneedles for drug delivery and monitoring. Microfluidic Devices for Biomedical Applications
No full textSupplemental_Material – Supplemental material for User testing of the psychometric properties of pictorial-based disability assessment Longshi Scale by healthcare professionals and non-professionals: a Chinese study in Shenzhen
No full textSupplemental material, Supplemental_Material for User testing of the psychometric properties of pictorial-based disability assessment Longshi Scale by healthcare professionals and non-professionals: a Chinese study in Shenzhen by Yulong Wang, Shanshan Guo, Jiejiao Zheng, Qing Mei Wang, Yuling Zhang, Zhenwen Liang, Lihai Zhang, Yi Yang, Haohan Zhai, Miaoling Chen, Yuzhen Wang, Yawei Li, Xing Lyu, Xuhui Li, Hongli Geng, Xiaolong Zhu, Fei Yu, Jian Yuan, Jing Zhou, Fang Liu, Haoming Luo, Jianjun Long, Wensheng Chen, Hua Li, Guanqi Fu, Chunxiu Zhou, Jiehong Zhang, Yao Wang, Yongyang Huo, Xiujun Ke, Yuanyuan Zeng, Jiayu Liu, Hailan Xing, Huixiang Xiao, Rui Jiao, Miao Wu, Qiang Tang and Xun Luo in Clinical Rehabilitation</p
Identification and Validation of Glycosylation-Related Genes in Obesity and MASH: Insights from Human Liver Samples and a High-Fat Diet Mouse Model
No full textWeihua Yu,* Jionghuang Chen,* Shengxi Jin, Xiaoxiao Fan, Xiujun Cai Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiujun Cai, Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, 310000, People’s Republic of China, Tel/Fax +86-571-86006617, Email [email protected]: Obesity is reaching epidemic proportions in the developed world. The biosynthesis and degradation of human glycoproteins take place at the highest level in the liver. However, the association between glycosylation and the factors affecting obesity and metabolism-associated steatohepatitis (MASH) is still unclear.Materials and Methods: Gene expression data of liver samples from obese patients were retrieved from GSE83452 and GSE89632 databases. Difference analysis and machine learning were used to identify hub genes involved in glycosylation and associated with the response of weight loss treatment. A total of 7 glycosylation-related hub genes were identified and then subjected to correlation analysis, immune cells infiltration analysis and ROC (Receiver Operating Characteristic) analysis. We also evaluated the potential function of 7 hub genes in obesity patients. MASH mice were used to validate the glycosylation-related hub genes.Results: A total of 25 overlapped glycosylation-related genes were identified by DEGs analysis. ACER2, STX17, ARF5, GPC4, ENTPD5, NANP, and DPY19L2 were identified as hub genes. Among these hub genes, ACER2, STX17, ARF5, and ENTPD5 were also differential expressed in MASH patients. ENTPD5 showed increased transcription in obese MASH mice.Conclusion: The current study identified seven glycosylation-related genes, ACER2, STX17, ARF5, GPC4, ENTPD5, NANP, and DPY19L2, that might play key roles in the development of obesity. ENTPD5 might play a key role in the development of MASH. These findings provide fresh perspectives for expanding the investigation of obesity and MASH.Keywords: obesity, MASH, glycosylation, machine learnin
Remotely controllable supramolecular rotor mounted inside a porphyrinic cage
No full text© 2021 Elsevier Inc.The confinement of molecular machines into nanostructured cages and controlling their functions by external stimuli holds great potential for the creation of smart functional materials that imitate the embodied intelligence of biological processes. Herein, we report the construction of a supramolecular rotor in a porous Zn-metallated porphyrinic cage (1) by encapsulation of a tetrazine-based linear axle (LA) via metal-ligand coordination bond, followed by post-assembly modification to append a controllable side arm to LA via inverse electron demand Diels-Alder (IEDDA) reaction. While the rotor alone shows nearly no motion, the addition of pyridine derivatives as a zinc coordinating ligand results in both 90° jump-like rotary motion of the rotor and slow tumbling motion of the rotor axle in a stochastic manner. Interestingly, the dual motions of the rotor can be reversibly controlled by the UV and visible light-induced coordination and dissociation of an azopyridine-based ligand with Zn centers as a signal transducer.11Nsciescopu
Supramolecular Fullerene Tetramers Concocted with Porphyrin Boxes Enable Efficient Charge Separation and Delocalization
No full textHerein, we report a novel porphyrin/fullerene supramolecular cocrystal using a shape-persistent zinc-metalated porphyrin box (Zn-PB) and C-60/C-70. An unprecedented arrangement of a tightly packed square-planar core of four C-60 or C-70 surrounded by six cube-shaped Zn-PBs was observed. This unique packing promotes strong charge transfer (CT) interactions between the two components in the ground state and formation of charge-separated states with very long lifetimes in the excited state and enables unusually high photoconductivity. Quantum chemical calculations show that these features are enabled by delocalized orbitals that promote the CT, on one hand, and that are spatially separated from each other, on the other hand. This work may open a new avenue to design novel electron donor/acceptor architectures for artificial photosynthesis.11Nsciescopu
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