Blocking tau transmission by biomimetic graphene nanoparticles.

Tauopathies are a class of neurodegenerative diseases resulting in cognitive dysfunction, executive dysfunction, and motor disturbance. The primary pathological feature of tauopathies is the presence of neurofibrillary tangles in the brain composed of tau protein aggregates. Moreover, tau aggregates can spread from neuron to neuron and lead to the propagation of tau pathology. Although numerous small molecules are known to inhibit tau aggregation and block tau cell-to-cell transmission, it is still challenging to use them for therapeutic applications due to poor specificity and low blood-brain barrier (BBB) penetration. Graphene nanoparticles were previously demonstrated to penetrate the BBB and are amenable to functionalization for targeted delivery. Moreover, these nanoscale biomimetic particles can self-assemble or assemble with various biomolecules including proteins. In this paper, we show that graphene quantum dots (GQDs), as graphene nanoparticles, block the seeding activity of tau fibrils by inhibiting the fibrillization of monomeric tau and triggering the disaggregation of tau filaments. This behavior is attributed to electrostatic and π–π stacking interactions of GQDs with tau. Overall, our studies indicate that GQDs with biomimetic properties can efficiently inhibit and disassemble pathological tau aggregates, and thus block tau transmission, which supports their future developments as a potential treatment for tauopathies.</p

Biomaterial-enabled 3D cell culture technologies for extracellular vesicle manufacturing

Extracellular vesicles (EVs) are lipid-based particles naturally released from cells and recognized as promising drug delivery vehicles for improving therapeutic outcomes. Efficient manufacturing of therapeutic EVs have been challenging for their clinical translations. Three-dimensional (3D) cell cultures enabled by biomaterial scaffolds have been used as a platform for improving EV manufacturing compared to conventional methods such as isolation from bodily fluids and standard Petri-dish cell culture. Recent studies on 3D culture derived EV production prove it to enhance the EV yield, functional cargos, and therapeutic efficacies. However, there are still challenges with scaling up 3D cell culture production platforms for industrial use. Hence, there is a high demand for designing, optimizing, and implementing large scale EV manufacturing platforms derived from 3D cell cultures. We will first review the current advances of biomaterial-enabled 3D cell cultures in EV manufacturing, followed by the effect of these 3D cell culture platforms on the EV yield, the EV quality, and therapeutic efficacies. Lastly, we will discuss the key challenges and potential for implementing biomaterial-enabled 3D culture in EV manufacturing for large scale processes in the industrial use.</p

Additional file 1 of Prevalence and sociodemographic correlates of food insecurity among post-secondary students and non-students of similar age in Canada

Supplementary Material

DataSheet1_Chirality-enhanced transport and drug delivery of graphene nanocarriers to tumor-like cellular spheroid.pdf

Chirality, defined as “a mirror image,” is a universal geometry of biological and nonbiological forms of matter. This geometry of molecules determines how they interact during their assembly and transport. With the development of nanotechnology, many nanoparticles with chiral geometry or chiroptical activity have emerged for biomedical research. The mechanisms by which chirality originates and the corresponding synthesis methods have been discussed and developed in the past decade. Inspired by the chiral selectivity in life, a comprehensive and in-depth study of interactions between chiral nanomaterials and biological systems has far-reaching significance in biomedicine. Here, we investigated the effect of the chirality of nanoscale drug carriers, graphene quantum dots (GQDs), on their transport in tumor-like cellular spheroids. Chirality of GQDs (L/D-GQDs) was achieved by the surface modification of GQDs with L/D-cysteines. As an in-vitro tissue model for drug testing, cellular spheroids were derived from a human hepatoma cell line (i.e., HepG2 cells) using the Hanging-drop method. Our results reveal that the L-GQDs had a 1.7-fold higher apparent diffusion coefficient than the D-GQDs, indicating that the L-GQDs can enhance their transport into tumor-like cellular spheroids. Moreover, when loaded with a common chemotherapy drug, Doxorubicin (DOX), via π-π stacking, L-GQDs are more effective as nanocarriers for drug delivery into solid tumor-like tissue, resulting in 25% higher efficacy for cancerous cellular spheroids than free DOX. Overall, our studies indicated that the chirality of nanocarriers is essential for the design of drug delivery vehicles to enhance the transport of drugs in a cancerous tumor.</p

Chirality-enhanced transport and drug delivery of graphene nanocarriers to tumor-like cellular spheroid

Chirality, defined as "a mirror image," is a universal geometry of biological and nonbiological forms of matter. This geometry of molecules determines how they interact during their assembly and transport. With the development of nanotechnology, many nanoparticles with chiral geometry or chiroptical activity have emerged for biomedical research. The mechanisms by which chirality originates and the corresponding synthesis methods have been discussed and developed in the past decade. Inspired by the chiral selectivity in life, a comprehensive and in-depth study of interactions between chiral nanomaterials and biological systems has far-reaching significance in biomedicine. Here, we investigated the effect of the chirality of nanoscale drug carriers, graphene quantum dots (GQDs), on their transport in tumor-like cellular spheroids. Chirality of GQDs (L/D-GQDs) was achieved by the surface modification of GQDs with L/D-cysteines. As an in-vitro tissue model for drug testing, cellular spheroids were derived from a human hepatoma cell line (i.e., HepG2 cells) using the Hanging-drop method. Our results reveal that the L-GQDs had a 1.7-fold higher apparent diffusion coefficient than the D-GQDs, indicating that the L-GQDs can enhance their transport into tumor-like cellular spheroids. Moreover, when loaded with a common chemotherapy drug, Doxorubicin (DOX), via π-π stacking, L-GQDs are more effective as nanocarriers for drug delivery into solid tumor-like tissue, resulting in 25% higher efficacy for cancerous cellular spheroids than free DOX. Overall, our studies indicated that the chirality of nanocarriers is essential for the design of drug delivery vehicles to enhance the transport of drugs in a cancerous tumor.</p

Additional file 2 of Prevalence and sociodemographic correlates of food insecurity among post-secondary students and non-students of similar age in Canada

Supplementary Material

Selective Hydrolysis of Primary and Secondary Amides Enabled by Visible Light

Amide hydrolysis is a fundamentally important transformation in organic chemistry. Developing hydrolysis procedures under mild conditions with a broad substrate scope is desirable. Herein, by leveraging a photoresponsive auxiliary o-nitroanilide, we established a mild two-step protocol for the hydrolysis of primary and secondary amides. This protocol is driven by visible light irradiation at room temperature under neutral conditions, which tolerates numerous acid- and base-sensitive functional groups. Various drugs, natural product-, and amino acid-derived amides can be selectively hydrolyzed

A Polyurethane Organic Framework for Flexible Al–Air Batteries

Flexible Al–air batteries with hydrogels are regarded as a promising power source owing to their high specific capacity, their high ionic conductivity, and having no leakage. However, the mechanical properties of the hydrogels remain unresolved. Here, we present a polyurethane organic framework (POF) employing a polyurethane skeleton as an internal support for poly­(acrylic acid) (PAA) hydrogel, where the POF can exhibit high strength and toughness, and an Al–air battery using the POF can output good electrochemical properties. The results demonstrate that the tensile stress of 30 ppi POF is 49.5 kPa owing to the stress-transfer mechanism, while that of PAA is only 3.1 kPa. Compared to that of the PAA hydrogel, the discharging capacity of Al–air batteries with 20 ppi POF can be increased by 79 mAh cm–2 at a current density of 1 mA cm–2, which can be attributed to corrosion inhibition and the surface roughness change of the POF during the discharging process. This work will deliver a selectable strategy for a trade-off between mechanical and electrochemical properties

Image_5_Construction of an Immune Cell Infiltration Score to Evaluate the Prognosis and Therapeutic Efficacy of Ovarian Cancer Patients.tif

BackgroundOvarian cancer (OC) is an immunogenetic disease that contains tumor-infiltrating lymphocytes (TILs), and immunotherapy has become a novel treatment for OC. With the development of next-generation sequencing (NGS), profiles of gene expression and comprehensive landscape of immune cells can be applied to predict clinical outcome and response to immunotherapy.MethodsWe obtained data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and applied two computational algorithms (CIBERSORT and ESTIMATE) for consensus clustering of immune cells. Patients were divided into two subtypes using immune cell infiltration (ICI) levels. Then, differentially expressed genes (DEGs) associated with immune cell infiltration (ICI) level were identified. We also constructed ICI score after principle-component analysis (PCA) for dimension reduction.ResultsPatients in ICI cluster B had better survival than those in ICI cluster A. After construction of ICI score, we found that high ICI score had better clinical OS and significantly higher tumor mutation burden (TMB). According to the expression of immune checkpoints, the results showed that patients in high ICI group showed high expression of CTLA4, PD1, PD-L1, and PD-L2, which implies that they might benefit from immunotherapy. Besides, patients in high ICI group showed higher sensitivity to two first-line chemotherapy drugs (Paclitaxel and Cisplatin).ConclusionICI score is an effective prognosis-related biomarker for OC and can provide valuable information on the potential response to immunotherapy.</p

Image_2_Construction of an Immune Cell Infiltration Score to Evaluate the Prognosis and Therapeutic Efficacy of Ovarian Cancer Patients.tif

BackgroundOvarian cancer (OC) is an immunogenetic disease that contains tumor-infiltrating lymphocytes (TILs), and immunotherapy has become a novel treatment for OC. With the development of next-generation sequencing (NGS), profiles of gene expression and comprehensive landscape of immune cells can be applied to predict clinical outcome and response to immunotherapy.MethodsWe obtained data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases and applied two computational algorithms (CIBERSORT and ESTIMATE) for consensus clustering of immune cells. Patients were divided into two subtypes using immune cell infiltration (ICI) levels. Then, differentially expressed genes (DEGs) associated with immune cell infiltration (ICI) level were identified. We also constructed ICI score after principle-component analysis (PCA) for dimension reduction.ResultsPatients in ICI cluster B had better survival than those in ICI cluster A. After construction of ICI score, we found that high ICI score had better clinical OS and significantly higher tumor mutation burden (TMB). According to the expression of immune checkpoints, the results showed that patients in high ICI group showed high expression of CTLA4, PD1, PD-L1, and PD-L2, which implies that they might benefit from immunotherapy. Besides, patients in high ICI group showed higher sensitivity to two first-line chemotherapy drugs (Paclitaxel and Cisplatin).ConclusionICI score is an effective prognosis-related biomarker for OC and can provide valuable information on the potential response to immunotherapy.</p