High-molecular-weight polyvinylamine (PVAm)/piperazine glycinate (PG) membranes were successfully synthesized for CO2/N2 separation from flue gas. PVAm with different molecular weights was ...synthesized through free radical polymerization by adjusting the monomer concentration and initiator amount. The synthesized PVAm showed both a higher molecular weight and a higher solution viscosity than the commercially available PVAm (Lupamin® 9095 from BASF Corporation). The high viscosity of the PVAm solution at a low concentration allowed the preparation of much thinner membranes. It could also help reducing penetration of the polymer solution into the pores of the substrate, further reducing the mass transfer resistance. Consequently, a high CO2 permeance could be obtained from thin membranes with the thickness of 100–200nm. In the membrane, PVAm acted as the fixed-site carrier for CO2 facilitated transport whereas PG was incorporated into the PVAm polymer matrix and served as the mobile carrier. The PVAm/PG blend solution was coated onto different substrates including polyethersulfone (PES) and polysulfone (PSf) substrates. Sodium dodecyl sulfate (SDS) surfactant was incorporated in the coating solution to improve the adhesion between the membrane layer and the substrate in some cases. The resultant PVAm/PG membranes exhibited a high CO2 permeance of about 1100 GPU and a high CO2/N2 mixed gas selectivity of more than 140 at the typical flue gas temperature of 57°C along with 17% water vapor.
•High-molecular-weight polyvinylamine/piperazine glycinate membranes synthesized.•PVAm with different molecular weights was synthesized.•The synthesized PVAm showed a much higher molecular weight than Lupamin®.•Sodium dodecyl sulfate was incorporated to improve adhesion to the substrate.•The resultant membrane showed high CO2 permeance and high CO2/N2 selectivity.
Intracellular delivery is a critical step in biological discoveries and has been widely utilized in biomedical research. A variety of molecular tools have been developed for cell-based gene ...therapies, including FDA approved CAR-T immunotherapy, iPSC, cell reprogramming and gene editing. Despite the inspiring results of these applications, intracellular delivery of foreign molecules including nucleic acids and proteins remains challenging. Efficient yet non-invasive delivery of biomolecules in a high-throughput manner has thus long fascinates the scientific community. As one of the most popular non-viral technologies for cell transfection, electroporation has gone through enormous development with the assist of nanotechnology and microfabrication. Emergence of miniatured electroporation system brought up many merits over the weakness of traditional electroporation system, including precise dose control and high cell viability. These new generation of electroporation systems are of considerable importance to expand the biological applications of intracellular delivery, bypassing the potential safety issue of viral vectors. In this review, we will go over the recent progresses in the electroporation-based intracellular delivery and several potential applications of cutting-edge research on the miniatured electroporation, including gene therapy, cellular reprogramming and intracellular probe.
New amine-containing polymer/zeolite Y composite membranes were successfully synthesized for CO2/N2 separation from flue gas. The polyvinylamine (PVAm) with a high molecular weight (MW¯=719,000) was ...synthesized and used as the fixed-site carrier for CO2 facilitated transport. The PVAm was incorporated with different aminoacid salts (mobile carriers), including potassium glycinate (KG), lithium glycinate (LiG) and piperazine glycinate (PG). The amine-containing polymer blend solution was coated onto a zeolite Y seed layer on top of a polyethersulfone (PES) substrate. The composite membrane with a selective amine layer thickness of more than 200nm showed a better CO2/N2 separation performance compared to the membrane without the zeolite Y seed layer, which was due to the fact that the zeolite Y layer had a smaller interparticle pore size than the PES substrate, resulting in minimizing the penetration of amine-containing polymer solution into the pores underneath and thus reducing the mass transfer resistance of CO2 molecules through the membrane. The effects of different kinds of mobile carriers and various compositions and thicknesses of the amine-containing polymer layer were investigated. The resultant amine-containing polymer/zeolite Y composite membrane exhibited a CO2 permeance up to ~1100GPU and a CO2/N2 mixed gas selectivity of at least 200 at the typical flue gas temperature of 57°C. This high separation performance showed a great potential for the application of carbon capture from flue gas.
•New amine-containing polymer/zeolite Y composite membranes were synthesized.•Zeolite Y layer improved performance when the amine layer was more than 200nm.•Effects of mobile carrier, composition and thickness on performance were studied.•The membrane showed ~1100GPU and >200 CO2/N2 selectivity at 57°C.
Tumour-targeted immunotherapy offers the unique advantage of specific tumouricidal effects with reduced immune-associated toxicity. However, existing platforms suffer from low potency, inability to ...generate long-term immune memory and decreased activities against tumour-cell subpopulations with low targeting receptor levels. Here we adopted a modular design approach that uses colloidal nanoparticles as substrates to create a multivalent bi-specific nanobioconjugate engager (mBiNE) to promote selective, immune-mediated eradication of cancer cells. By simultaneously targeting the human epidermal growth factor receptor 2 (HER2) expressed by cancer cells and pro-phagocytosis signalling mediated by calreticulin, the mBiNE stimulated HER2-targeted phagocytosis and produced durable antitumour immune responses against HER2-expressing tumours. Interestingly, although the initial immune activation mediated by the mBiNE was receptor dependent, the subsequent antitumour immunity also generated protective effects against tumour-cell populations that lacked the HER2 receptor. Thus, the mBiNE represents a new targeted, nanomaterial-immunotherapy platform to stimulate innate and adaptive immunity and promote a universal antitumour response.
A spiral-wound membrane module comprising face compression “O” rings for effective seal of gases was developed, including a spiral-wound membrane element, Plexiglas fiber-reinforced plastic tube, and ...membrane housing. The spiral-wound membrane modules demonstrated essentially no leakage. The concentration polarization phenomenon was observed at a dry feed gas flow rate of less than 1000 sccm before humidification. Hence, the performances of the spiral-wound membrane modules were evaluated using both dry feed and sweep gas flow rates each at 1000 sccm before humidification at the typical flue gas temperature of 57 °C. The feed and sweep gas pressures were at 1.5 and 1 psig, respectively. By using either a simulated flue gas or an actual flue gas, the spiral-wound membrane modules showed similar performance results with a CO2 permeance of greater than 800 GPU and a CO2/N2 selectivity of more than 140, which were essentially identical to the results obtained from the flat-sheet membrane used for the module fabrication and tested in laboratory with the simulated flue gas. The pressure drops of the modules were satisfactory, i.e., less than 1.5 psi/m. During the field test using the actual flue gas at the National Carbon Capture Center in Wilsonville, Alabama, the performances of the modules revealed some unexpected issues including the feed spacer indentations on the membrane selective layer and the leakage at glue lines. These issues were resolved by improving the spiral-wound membrane module fabrication using a smoother feed spacer and a longer glue curing time. The field test results of the modules have shown their good potential for the post-combustion CO2 capture from coal-fired power plants.
•A new spiral-wound membrane module with face compression “O” rings was fabricated.•Spiral-wound membrane modules were tested with both simulated and actual flue gas.•Concentration polarization phenomenon was observed at low feed-gas flow rates.•High performance was obtained with an acceptable pressure drop of <1.5 psi/m.•Field test result has shown the potential for CO2 capture in coal-fired power plants.
Abstract Although amyloid plaques and neurofibrillary pathology play important roles in Alzheimer disease (AD), our understanding of AD is incomplete, and the contribution of microglia and iron to ...neurodegeneration is unknown. High-field magnetic resonance imaging (MRI) is exquisitely sensitive to microscopic iron. To explore iron-associated neuroinflammatory AD pathology, we studied AD and control human brain specimens by (1) performing ultra-high resolution ex vivo 7 Tesla MRI, (2) coregistering the MRI with successive histologic staining for iron, microglia, amyloid beta, and tau, and (3) quantifying the relationship between magnetic resonance signal intensity and histological staining. In AD, we identified numerous small MR hypointensities primarily within the subiculum that were best explained by the combination of microscopic iron and activated microglia ( p = 0.025), in contradistinction to the relatively lesser contribution of tau or amyloid. Neuropathologically, this suggests that microglial-mediated neurodegeneration may occur in the hippocampal formation in AD and is detectable by ultra-high resolution MRI.
Exosomes are attractive as nucleic-acid carriers because of their favourable pharmacokinetic and immunological properties and their ability to penetrate physiological barriers that are impermeable to ...synthetic drug-delivery vehicles. However, inserting exogenous nucleic acids, especially large messenger RNAs, into cell-secreted exosomes leads to low yields. Here we report a cellular-nanoporation method for the production of large quantities of exosomes containing therapeutic mRNAs and targeting peptides. We transfected various source cells with plasmid DNAs and stimulated the cells with a focal and transient electrical stimulus that promotes the release of exosomes carrying transcribed mRNAs and targeting peptides. Compared with bulk electroporation and other exosome-production strategies, cellular nanoporation produced up to 50-fold more exosomes and a more than 10
-fold increase in exosomal mRNA transcripts, even from cells with low basal levels of exosome secretion. In orthotopic phosphatase and tensin homologue (PTEN)-deficient glioma mouse models, mRNA-containing exosomes restored tumour-suppressor function, enhanced inhibition of tumour growth and increased survival. Cellular nanoporation may enable the use of exosomes as a universal nucleic-acid carrier for applications requiring transcriptional manipulation.
Nanomedicine is a burgeoning industry but an understanding of the interaction of nanomaterials with the immune system is critical for clinical translation. Macrophages play a fundamental role in the ...immune system by engulfing foreign particulates such as nanoparticles. When activated, macrophages form distinct phenotypic populations with unique immune functions, however the mechanism by which these polarized macrophages react to nanoparticles is unclear. Furthermore, strategies to selectively evade activated macrophage subpopulations are lacking. Here we demonstrate that stimulated macrophages possess higher phagocytic activities and that classically activated (M1) macrophages exhibit greater phagocytic capacity than alternatively activated (M2) macrophages. We show that modification of nanoparticles with polyethylene-glycol results in decreased clearance by all macrophage phenotypes, but importantly, coating nanoparticles with CD47 preferentially lowers phagocytic activity by the M1 phenotype. These results suggest that bio-inspired nanoparticle surface design may enable evasion of specific components of the immune system and provide a rational approach for developing immune tolerant nanomedicines.
The naked mole rat (Heterocephalus glaber) is a strictly subterranean, extraordinarily long-lived eusocial mammal. Although it is the size of a mouse, its maximum lifespan exceeds 30 years, making ...this animal the longest-living rodent. Naked mole rats show negligible senescence, no age-related increase in mortality, and high fecundity until death. In addition to delayed ageing, they are resistant to both spontaneous cancer and experimentally induced tumorigenesis. Naked mole rats pose a challenge to the theories that link ageing, cancer and redox homeostasis. Although characterized by significant oxidative stress, the naked mole rat proteome does not show age-related susceptibility to oxidative damage or increased ubiquitination. Naked mole rats naturally reside in large colonies with a single breeding female, the 'queen', who suppresses the sexual maturity of her subordinates. They also live in full darkness, at low oxygen and high carbon dioxide concentrations, and are unable to sustain thermogenesis nor feel certain types of pain. Here we report the sequencing and analysis of the naked mole rat genome, which reveals unique genome features and molecular adaptations consistent with cancer resistance, poikilothermy, hairlessness and insensitivity to low oxygen, and altered visual function, circadian rythms and taste sensing. This information provides insights into the naked mole rat's exceptional longevity and ability to live in hostile conditions, in the dark and at low oxygen. The extreme traits of the naked mole rat, together with the reported genome and transcriptome information, offer opportunities for understanding ageing and advancing other areas of biological and biomedical research.
Microglial involvement in Alzheimer's disease (AD) pathology has emerged as a risk-determining pathogenic event. While apolipoprotein E (APOE) is known to modify AD risk, it remains unclear how ...microglial apoE impacts brain cognition and AD pathology. Here, using conditional mouse models expressing apoE isoforms in microglia and central nervous system-associated macrophages (CAMs), we demonstrate a cell-autonomous effect of apoE3-mediated microglial activation and function, which are negated by apoE4. Expression of apoE3 in microglia/CAMs improves cognitive function, increases microglia surrounding amyloid plaque and reduces amyloid pathology and associated toxicity, whereas apoE4 expression either compromises or has no effects on these outcomes by impairing lipid metabolism. Single-cell transcriptomic profiling reveals increased antigen presentation and interferon pathways upon apoE3 expression. In contrast, apoE4 expression downregulates complement and lysosomal pathways, and promotes stress-related responses. Moreover, in the presence of mouse endogenous apoE, microglial apoE4 exacerbates amyloid pathology. Finally, we observed a reduction in Lgals3-positive responsive microglia surrounding amyloid plaque and an increased accumulation of lipid droplets in APOE4 human brains and induced pluripotent stem cell-derived microglia. Our findings establish critical isoform-dependent effects of microglia/CAM-expressed apoE in brain function and the development of amyloid pathology, providing new insight into how apoE4 vastly increases AD risk.
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