Functional activity, functional connectivity and complex network biomarkers of progressive hyposmia Parkinson’s disease with no cognitive impairment: evidences from resting-state fMRI study

BackgroundOlfactory dysfunction stands as one of the most prevalent non-motor symptoms in the initial stage of Parkinson’s disease (PD). Nevertheless, the intricate mechanisms underlying olfactory deficits in Parkinson’s disease still remain elusive.MethodsThis study collected rs-fMRI data from 30 PD patients [15 with severe hyposmia (PD-SH) and 15 with no/mild hyposmia (PD-N/MH)] and 15 healthy controls (HC). To investigate functional segregation, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were utilized. Functional connectivity (FC) analysis was performed to explore the functional integration across diverse brain regions. Additionally, the graph theory-based network analysis was employed to assess functional networks in PD patients. Furthermore, Pearson correlation analysis was conducted to delve deeper into the relationship between the severity of olfactory dysfunction and various functional metrics.ResultsWe discovered pronounced variations in ALFF, ReHo, FC, and topological brain network attributes across the three groups, with several of these disparities exhibiting a correlation with olfactory scores.ConclusionUsing fMRI, our study analyzed brain function in PD-SH, PD-N/MH, and HC groups, revealing impaired segregation and integration in PD-SH and PD-N/MH. We hypothesize that changes in temporal, frontal, occipital, and cerebellar activities, along with aberrant cerebellum-insula connectivity and node degree and betweenness disparities, may be linked to olfactory dysfunction in PD patients

Breaking Boundaries: Chronic Diseases and the Frontiers of Immune Microenvironments

The immune microenvironment includes immune cells, cytokines, extracellular matrix, vesicles, etc. The interactions between these components form a unique local immune microecology. Although immunity serves as the defense against external pathogens, aberrant immune activation often contributes to disease development. Chronic diseases, a broad category of noncommunicable conditions characterized by long latency and prolonged course, are increasingly recognized for their intricate relationship with the immune microenvironment. Herein, we comprehensively summarize how the immune microenvironment, through its complex regulatory network, influences the progression and manifestation of chronic diseases. We further explore the potential of targeting the immune microenvironment as a therapeutic strategy, aiming to provide new insights and directions for the prevention, diagnosis, and treatment of chronic diseases

Aquatic micro-pollutants removal with a biocatalytic membrane prepared by metal chelating affinity membrane chromatography

Biocatalytic membranes are promising to remove micro-pollutants in aqueous environment due to their mild and green operation condition. However, more efforts need to be devoted to improving their removal efficiency and stability. In this study, metal chelating affinity membrane chromatography (MCAMC) was used to construct a biocatalytic membrane by selectively capturing laccase from a crude fermentation broth. Metal ions had a significant effect on the activity of the immobilized laccase and copper ion was the best choice. A pH of 4.5 was selected for laccase adsorption and its loading seemed the same under flow rates from 0.5 to 10 mL min(-1) thanks to the inherent convective transport of membrane chromatography. The pH value and salt concentration in the storage buffer had an obvious effect on the stability of the immobilized laccase, and the prepared biocatalytic membrane retained 87% of initial activity after 20 days storage. When applying such membrane to micro-pollutant removal (taking bisphenol A (BPA) as an example), a high BPA removal efficiency (99.3%) could be obtained. The biocatalytic membranes could be operated at a high flux of 50 L m(-2) h(-1) without recycling the permeate into the feed, and its throughput and BPA removal rate were superior to the most results in the literature. However, BPA removal decline (from 99.6% to 56.6% after five cycles) occurred during the successive water treatment due to the membrane fouling caused by BPA polymerization products. Membrane regeneration could be achieved by simple elution-cleaning-reloading, and the laccase activity and BPA removal were fully recovered. (C) 2017 Elsevier B.V. All rights reserved.</p

Membrane chromatography for fast enzyme purification, immobilization and catalysis: A renewable biocatalytic membrane

Enzyme purification and subsequent immobilization usually require multiple steps and consume plenty of chemicals. Traditional dipping incubation operation is lengthy and the interior of porous carrier is not fully exploited due to the diffusion barrier. To solve these problems, one-step enzyme purification and immobilization was developed based on membrane chromatography concept. A membrane adsorber was prepared by polydopamine coating on a PVDF microfiltration membrane (or on a cheap and disposable cellulose filter paper) and subsequent polyethyleneimine grafting, without any solvent usage. Laccase was selectively immobilized on such membrane adsorber (enzyme activity: 39.9 +/- 4.4 U/mL; expressed activity: 19.6 +/- 3.0%) by directly capturing it from a crude fermentation broth without pH adjustment under flow through mode. The immobilized laccase had a high purity of 92.2%, while the membrane permeability decreased due to the adsorption of laccase and impurities (&quot;membrane fouling&quot;). Thanks to the dominant convective transport, the enzyme loading was high and much faster than that by dipping incubation (5 min vs. 80 min). Moreover, enzyme reloading on membrane adsorber was easily realized by reversible desorption-adsorption process. The constructed biocatalytic membrane exhibited a commendable reusability for bisphenol A (BPA) removal only driven by its gravity.</p

One-step purification of alpha(1)-antitrypsin by regulating polyelectrolyte ligands on mussel-inspired membrane adsorber

One-step purification of biomolecules from complex feed is challenging with commercial membrane adsorbers since it is difficult to screen and regulate the ligands on the membrane with traditional techniques for removal of various impurities. By readily grafting cationic polyelectrolyte ligands on a polydopamine (PDA)-coated membrane, a membrane adsorber with suitable ligand (750 kDa polyethylenimine, PEI) was selected to achieve one-step purification of arantitrypsin (AAT) from pretreated human plasma fraction W. It was found that ligand structure and molecular weight showed a significant effect on the properties and separation performance of membrane adsorbers. The attached polyelectrolytes increased membrane hydrophilicity but caused an enhancement of filtration resistance, and quaternization of the ligands (PEI and polyallylamine) further improved the hydrophilicity but decreased the charge quantity. By further screening elution salt concentration, flow rate, buffer pH, loading volume as well as molecular weight of PEI ligands, a high activity recovery of 96.6% and a high purity of 94.6% of AAT were obtained by one-step membrane chromatography, which was even better than those by multiple-step method. This could be owing to the special multilayer structure of PEI chains, which could suppress the impurity protein binding on the adsorption sites by exclusion effect. The present work not only provides new insights into the purification of biomolecules from complex streams with polyelectrolytecoupled membrane adsorbers, but also offers a new approach to design the ligands on membrane adsorber for specific application.</p

Polydopamine meets porous membrane: A versatile platform for facile preparation of membrane adsorbers

Polydopamine, as an intermediate layer coated on PES membrane, was applied to fabricate various membrane adsorbers. Anion-exchange, hydrophobic interaction and affinity membrane adsorbers prepared by this facile method exhibited a high selectivity in fractionation of IgG (immunoglobulin)/HSA (human serum albumin) mixture. The anion-exchange membrane adsorber containing polyethylenimine (PEI) improved the HSA purity from 17.7% to 96.7%; The hydrophobic interaction membrane adsorber with Dodecyl mercaptan (DDM) as ligand obtained an IgG purity of 94.6%; Histidine attached affinity membrane chromatography achieved nearly a 100% purity of IgG. The present work indicated that the polydopamine layer not only activated membrane surface to attach various adsorptive ligands under the mild condition, but also reduced non-specific adsorption. Due to the versatile conjunction function, this facile mussel-inspired coating is also promising for the preparation of diverse membrane adsorbers. (C) 2016 Elsevier B.V. All rights reserved

Facile preparation of salt-tolerant anion-exchange membrane adsorber using hydrophobic membrane as substrate

In this study, a polyvinylidene fluoride (PVDF) hydrophobic membrane with high mechanical property was used as substrate to prepare salt-tolerant anion-exchange (STAE) membrane adsorber. Effective hydrophilization and functionalization of PVDF membrane was realized via polydopamine (PDA) deposition, thus overcoming the drawbacks of hydrophobic substrates including poor water permeability, inert property as well as severe non-specific adsorption. The following polyallylamine (PAH) coupling was carried out at pH 10.0, where unprotonated amine groups on PAH chains were more prone to couple with PDA. This membrane adsorber could remain 75% of protein binding capacity when NaCl concentration increased from 0 to 150 mM, while its protein binding capacity was independent of flow rate from 10 to 100 membrane volume (MV)/min due to its high mechanical strength (tensile strength: 43.58 +/- 2.30 MPa). With 200 mM NaCI addition at pH 7.5, high purity (above 99%) and high recovery (almost 100%) of Immunoglobulin G (IgG) were obtained when using the STAE membrane adsorber to separate IgG/human serum albumin (HSA) mixture, being similar to that without NaCI at pH 6.0 (both under the flow rate of 10-100 MV/min). Finally, the reliable reusability was confirmed by five reuse cycles of protein binding and elution operations. In comparison with commercial membrane adsorber, the new membrane adsorber exhibited a better mechanical property, higher IgG polishing efficiency and reusability, while the protein binding capacity was lower due to less NH2 density on the membrane. The outcome of this work not only offers a facile and effective approach to prepare membrane adsorbers based on hydrophobic membranes, but also demonstrates great potential of this new designed STAE membrane adsorbers for efficient monoclonal antibody (mAb) polishing. (C) 2017 Elsevier B.V. All rights reserved.</p

Aflatoxin B1 removal by multifunctional membrane based on polydopamine intermediate layer

A green and mild method for aflatoxin B1 (AFB1) removal from food and drinking is highly required due to its high toxicity to human. In this study, membrane technology was attempted firstly to remove AFB1 via two protocols, membrane adsorber and biocatalytic membrane. Four polyvinylidene fluoride microfiltration membranes with different pore size were used to prepare membrane adsorber through successively coating poly dopamine (PDA) and polyethyleneimine (PEI) on the membrane surface, and laccase was then loaded on the PDA/PEI-coated membrane to prepare biocatalytic membrane. Although biocatalytic membrane could remove AFB1 by both adsorption and enzymatic degradation, membrane adsorber outperformed thanks to its greater AFB1 removal efficiency (71%) and permeate flux (60 L.m(-2).h(-1)) under gravity-driven flow-through mode. Hydrogen bonding together with electrostatic attraction was its main adsorption mechanism, and thus alkaline cleaning could fully desorb AFB1 from the membrane and further degrade detached AFB1. The contaminative apple juice was treated by such membrane adsorber, which could achieve a constant AFB1 removal for 7 reuse cycles