Bioengineering strategies to enhance the natural targeting function of nanocarriers would expand their therapeutic applications. Here, we designed bioengineered stem cell membrane-functionalized ...nanocarriers (BSMNCs) harboring C-X-C chemokine receptor type 4 (CXCR4) to achieve robust targeting and also to increase their retention time in ischemic tissue. Stem cell membrane coated nanocarrier (SMNCs) or poly (lactic-co-glycolic acid) (PLGA) nanocarriers (PNCs) and BSMNCs were prepared by functionalizing PNCs with human adipose-derived stem cells (hASCs) membranes and hASCs engineered to overexpress CXCR4-receptor, respectively. The functionalization of PNCs with stem cell membranes derived from hASCs significantly enhance the nanocarrier penetration across endothelial cell barrier compare to PNCs. In addition, stem cell membrane functionalization on PNCs also significantly decreased the nanoparticles uptake in J774 (murine) and THP (human) macrophages respectively from 84% to 76%–29% and 24%. Interestingly, BSMNCs showed much higher level of accumulation in ischemic tissue than SMNCs. Systemic retro-orbital injection of BSMNCs loaded with VEGF into mice with hindlimb ischemia resulted substantially enhancement of blood reperfusion, muscle repair, and limb salvage compared to animals treated with SMNCs loaded with similar concentration of VEGF. The reported strategy could be used to create biocompatible and custom-tailored biomimetic nanoparticles with various hybrid functionalities, which may overcome the limitations of current nanoparticle-based therapeutic and imaging platforms.
The facile fabrication of thin and foldable self‐healing electronics on a poly(vinyl alcohol)/cellulose nanocrystal (PVA/CNC) composite film is reported. The self‐healing property of the PVA/CNC ...nanocomposite film can be activated by spraying water on the film surface, via dynamic formation of hydrogen bonding. The self‐healing efficiency of PVA/CNC is influenced by the content of CNC in the film, pH of the spraying solution, and the temperature. Via vacuum filtration and pattern transfer techniques, both a supercapacitor and a temperature sensor are fabricated on the same PVA/CNC film using gold nanosheet (AuNS) and polyaniline/multiwalled nanotube (PANI/MWCNT) electrodes. The fabricated supercapacitor with a gel‐type electrolyte exhibits a high electrochemical performance, and the thermoresistive temperature sensor shows a linear sensitivity with a fast response. Both devices exhibit superior mechanical stability and self‐healing property over 100 repetitive folding and five repetitive healing cycles, respectively, retaining the device performance owing to the percolated network of the conductive materials. This work demonstrates that our paper‐like thin PVA/CNC film‐based self‐healable devices can serve as highly durable and deformable electronics with longevity.
A paper‐like, thin, foldable, and self‐healable electronic based on poly(vinyl alcohol)/cellulose nanocrystal (PVA/CNC) nanocomposite film shows a water‐stimulated self‐healing property due to dynamic hydrogen bonding formation. A high‐performance planar supercapacitor and thermoresistive temperature sensor fabricated on the PVA/CNC substrate exhibits a high electrical self‐healing property after complete bisection as well as high mechanical stability under repetitive folding deformation.
As part of increased efforts to develop wearable healthcare devices for monitoring and managing physiological and metabolic information, stretchable electrochemical sweat sensors have been ...investigated. In this study, we report on the fabrication of a stretchable and skin-attachable electrochemical sensor for detecting glucose and pH in sweat. A patterned stretchable electrode was fabricated via layer-by-layer deposition of carbon nanotubes (CNTs) on top of patterned Au nanosheets (AuNS) prepared by filtration onto stretchable substrate. For the detection of glucose and pH, CoWO4/CNT and polyaniline/CNT nanocomposites were coated onto the CNT–AuNS electrodes, respectively. A reference electrode was prepared via chlorination of silver nanowires. Encapsulation of the stretchable sensor with sticky silbione led to a skin-attachable sweat sensor. Our sensor showed high performance with sensitivities of 10.89 μA mM–1 cm–2 and 71.44 mV pH–1 for glucose and pH, respectively, with mechanical stability up to 30% stretching and air stability for 10 days. The sensor also showed good adhesion even to wet skin, allowing the detection of glucose and pH in sweat from running while being attached onto the skin. This work suggests the application of our stretchable and skin-attachable electrochemical sensor to health management as a high-performance healthcare wearable device.
Background
Mechanisms underlying persistent food allergy (FA) are not well elucidated. The intestinal mucosa is the primary exposure route of food allergens. However, no study has examined intestinal ...metabolites associated with FA persistence. The goal of this study was to investigate intestinal metabolites and associated microbiomes in early life that aid in determining the development and persistence of FA.
Methods
We identified metabolomic alterations in the stool of infants according to FA by mass spectrometry‐based untargeted metabolome profiling. The targeted metabolomic analysis of bile acid metabolites and stool microbiome was performed. Bile acid metabolite composition in infancy was evaluated by characterizing the subjects at the age of 3 into FA remission and persistent FA.
Results
In untargeted metabolomics, primary bile acid biosynthesis was significantly different between subjects with FA and healthy controls. In targeted metabolomics for bile acids, intestinal bile acid metabolites synthesized by the alternative pathway were reduced in infants with FA than those in healthy controls. Subjects with persistent FA were also distinguished from healthy controls and those with FA remission by bile acid metabolites of the alternative pathway. These metabolites were negatively correlated with specific IgE levels in egg white. The abundance of intestinal Clostridia was decreased in the FA group and was correlated with ursodeoxycholic acid.
Conclusion
Intestinal bile acid metabolites of the alternative pathway could be predictive biomarkers for persistent FA in early childhood. These findings require replication in future studies.
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Allergic rhinitis (AR) phenotypes in childhood are unclear.
This study sought to determine AR phenotypes and investigate their natural course and clinical and transcriptomic ...characteristics.
Latent class trajectory analysis was used for phenotyping AR in 1050 children from birth through 12 years using a birth cohort study. Blood transcriptome analyses were performed to define the underlying mechanisms of each phenotype.
Five AR phenotypes were identified: early onset (n = 88, 8.4%), intermediate transient (n = 110, 10.5%), late onset (n = 209, 19.9%), very late onset (n=187, 17.8%), and never/infrequent (n = 456, 43.4%). Children with early-onset AR were associated with higher AR severity and sensitizations to foods at age 1 year and inhalants at age 3 years and asthma symptoms, but not with bronchial hyperresponsiveness (BHR). Children with late-onset AR phenotype associated with sensitizations to various foods at age 1 year but not from age 3 years, and to inhalants from age 7 years and with asthma with BHR. Children with very late–onset AR phenotype associated with sensitizations to foods throughout preschool age and to inhalants at ages 7 and 9 years and with asthma with BHR. Transcriptome analysis showed that early-onset AR was associated with viral/bacterial infection–related defense response, whereas late-onset AR was associated with T cell–related immune response.
Early-onset AR phenotype was associated with sensitization to foods and inhalants at an early age and asthma symptoms, but not with BHR, whereas very late– and late-onset AR phenotypes were positively associated with sensitization to inhalants and asthma with BHR. Transcriptomic analyses indicated that early- and late-onset AR phenotypes had distinct underlying mechanisms related to AR as well.
•Biofunctionalization with cell membranes gives cell like functions to NPs.•Cell membranes can be used for targeted drug delivery.•Preparations, characterization and application of cell membrane ...functionalized NPs are detailed.•The challenges and opportunities are presented.
Biological barriers, such as phagocytosis and nonspecific distribution, are major factors limiting the clinical translation of nanomedicine. Biomimetic and bioengineering strategies have been used to overcome these challenges. In particular, natural cell membrane-based biofunctionalized nanoparticles (CMFNPs) have gained widespread attention owing to their cell surface mimetic characteristics and tailored nanomaterial features. These hybrid nanocarriers show strong potential for the delivery of myriad therapeutic agents. Herein, we highlight the most recent advances in CMFNP-based drug delivery systems and address the challenges and opportunities in the field.
Recent advances in nanomaterials technology create the new possibility to fabricate high performance sensors. However, there has been limitations in terms of multivariate measurable and interoperable ...sensors. In this study, we fabricated an interoperable silver nanoparticle sensor fabricated by an aerodynamically focused nanomaterial (AFN) printing system which is a direct printing technique for inorganic nanomaterials onto a flexible substrate. The printed sensor exhibited the maximum measurable frequency of 850 Hz, and a gauge factor of 290.62. Using a fabricated sensor, we evaluated the sensing performance and demonstrated the measurement independency of strain and vibration sensing. Furthermore, using the proposed signal separation algorithm based on the Kalman filter, strain and vibration were each measured in real time. Finally, we applied the printed sensor to quadrotor condition monitoring to predict the motion of a quadrotor.
The reliable conductance modulation of synaptic devices is key when implementing high-performance neuromorphic systems. Herein, we propose a floating gate indium gallium zinc oxide (IGZO) synaptic ...device with an aluminum trapping layer to investigate the correlation between its diverse electrical parameters and pattern recognition accuracy. Basic synaptic properties such as excitatory postsynaptic current, paired pulse facilitation, long/short term memory, and long-term potentiation/depression are demonstrated in the IGZO synaptic transistor. The effects of pulse tuning conditions associated with the pulse voltage magnitude, interval, duration, and cycling number of the applied pulses on the conductance update are systematically investigated. It is discovered that both the nonlinearity of the conductance update and cycle-to-cycle variation should be critically considered using an artificial neural network simulator to ensure the high pattern recognition accuracy of Modified National Institute of Standards and Technology (MNIST) handwritten digit images. The highest recognition rate of the MNIST handwritten dataset is 94.06% for the most optimized pulse condition. Finally, a systematic study regarding the synaptic parameters must be performed to optimize the developed synapse device.
Background
Gut microbiota dysbiosis is linked to the development and responses of the immune system and can play an important role in the onset of allergic diseases including atopic dermatitis (AD). ...This study investigated the association between host genetics and the gut microbiota in AD.
Methods
A global gene expression profiling of the gut epithelial colonocytes, genetic variations analysis, and the gut microbial composition analysis were performed.
Results
This study identified the upregulation of PTGR2 (p = .028), a gene involved in prostaglandin catalysis and inflammatory responses, as a potential risk factor for AD. In subsequent fine mapping analysis using 17 single nucleotide polymorphisms (SNPs) of PTGR2 in 864 Korean subjects (420 AD patients and 444 unaffected controls), several SNPs and haplotypes showed significant associations with AD and its SCORing AD (SCORAD) values (p = .002). To investigate host‐microbial interactions, further gut microbiota data and genotypes were obtained from an independent cohort of 176 subjects (91 AD patients and 85 controls). From correlation analysis, a significantly negative association between SNP and Bifidobacterium abundance was observed in AD patients (p = .005). In additional observations of PTGR2‐associated downstream molecules, NRF2 (p = .004) and several antioxidant genes (GSTT1, GCLC, GPX1; p < .05) showed significantly reduced expression in AD patients.
Conclusions
Our current findings suggest that the interaction between PTGR2 dysregulated expression and a Bifidobacterium abundance affects a higher risk of AD and a more severe onset.
Chronic low back pain is a prevalent disability, often caused by intervertebral disc (IVD) degeneration. Mesenchymal stem cell (MSC) therapy could be a safe and feasible option for repairing the ...degenerated disc. However, for successful translation to the clinic, various challenges need to be overcome including unwanted adverse effects due to acidic pH, hypoxia, and limited nutrition. Matrilin-3 is an essential extracellular matrix (ECM) component during cartilage development and ossification and exerts chondrocyte protective effects.
This study evaluated the effects of matrilin-3-primed adipose-derived MSCs (Ad-MSCs) on the repair of the degenerated disc in vitro and in vivo. We determined the optimal priming concentration and duration and developed an optimal protocol for Ad-MSC spheroid generation.
Priming with 10 ng/ml matrilin-3 for 5 days resulted in the highest mRNA expression of type 2 collagen and aggrecan in vitro. Furthermore, Ad-MSC spheroids with a density of 250 cells/microwell showed the increased secretion of favorable growth factors such as transforming growth factor beta (TGF-β1), TGF-β2, interleukin-10 (IL-10), granulocyte colony-stimulating factor (G-CSF), and matrix metalloproteinase 1 (MMP1) and decreased secretion of hypertrophic ECM components. In addition, matrilin-3-primed Ad-MSC spheroid implantation was associated with optimal repair in a rabbit model.
Our results suggest that priming MSCs with matrilin-3 and spheroid formation could be an effective strategy to overcome the challenges associated with the use of MSCs for the treatment of IVD degeneration.
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