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2
Authors: Hu, Chaowei, et al
Published: Jan 2020
Authors: Hu, Chaowei, et al
Published: Jan 2020
Magnetic topological insulators (TI) provide an important material platform to explore quantum phenomena such as quantized anomalous Hall effect and Majorana modes, etc. Their successful material realization is thus essential for our fundamental understanding and potential technical revolutions. By realizing a bulk van der Waals material MnBi4Te7 with alternating septuple [MnBi2Te4] and quintuple [Bi2Te3] layers, we show that it is ferromagnetic in plane but antiferromagnetic along the c axis with an out-of-plane saturation field of ~0.22 T at 2 K. Our angle-resolved photoemission spectroscopy measurements and first-principles calculations further demonstrate that MnBi4Te7 is a Z2 antiferromagnetic TI with two types of surface states associated with the [MnBi2Te4] or [Bi2Te3] termination, respectively. Additionally, its superlattice nature may make various heterostructures of [MnBi2Te4] and [Bi2Te3] layers possible by exfoliation. Therefore, the low saturation field and the superlattice nature of MnBi4Te7 make it an ideal system to investigate rich emergent phenomena.
2
Authors: Muus, Christoph, et al
Published: Mar 2021
Authors: Muus, Christoph, et al
Published: Mar 2021
Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial–macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.
5
From Paper: Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3
Published: Mar 2021
From Paper: Lipid nanoparticle-mediated codelivery of Cas9 mRNA and single-guide RNA achieves liver-specific in vivo genome editing of Angptl3
Published: Mar 2021
Loss-of-function mutations in Angiopoietin-like 3 (Angptl3) are associated with lowered blood lipid levels, making Angptl3 an attractive therapeutic target for the treatment of human lipoprotein metabolism disorders. In this study, we developed a lipid nanoparticle delivery platform carrying Cas9 messenger RNA (mRNA) and guide RNA for CRISPR-Cas9–based genome editing of Angptl3 in vivo. This system mediated specific and efficient Angptl3 gene knockdown in the liver of wild-type C57BL/6 mice, resulting in profound reductions in serum ANGPTL3 protein, low density lipoprotein cholesterol, and triglyceride levels. Our delivery platform is significantly more efficient than the FDA-approved MC-3 LNP, the current gold standard. No evidence of off-target mutagenesis was detected at any of the nine top-predicted sites, and no evidence of toxicity was detected in the liver. Importantly, the therapeutic effect of genome editing was stable for at least 100 d after a single dose administration. This study highlights the potential of LNP-mediated delivery as a specific, effective, and safe platform for Cas9-based therapeutics.
6
From Paper: Synthesis and characterization of chemically crosslinked gelatin and chitosan to produce hydrogels for biomedical applications
From Paper: Synthesis and characterization of chemically crosslinked gelatin and chitosan to produce hydrogels for biomedical applications
Gelatin and chitosan polysaccharides were chemically modified to get methacrylate functionality to obtain biocompatible hydrogels for use as tissue engineering scaffolds. The methacrylation reaction was verified by 1H-NMR. The degree of methacrylation was varied from 7% to 40% by changing the molar ratio of polysaccharide to methacrylic anhydride and the type of polysaccharide utilized. After the modification, polysaccharide-based hydrogels were prepared by free-radical polymerization in the presence of UV light and Irgacure 184 as a photoinitiator. The physical, chemical, and mechanical performances of the hydrogels were further characterized. Also, the biodegradability and the viability of the polysaccharide hydrogels were investigated using fibroblast cells. These cells were seeded directly onto the hydrogel surface, populated the entirety of the hydrogel, and remained viable for up to 1 week. Altogether, the modified polysaccharides exhibit the properties which make them crucial for applications in the field of regenerative medicine.
6
From Paper: DNA-Grafted Hyaluronic Acid System with Enhanced Injectability and Biostability for Photo-Controlled Osteoarthritis Gene Therapy
From Paper: DNA-Grafted Hyaluronic Acid System with Enhanced Injectability and Biostability for Photo-Controlled Osteoarthritis Gene Therapy
Gene therapy is identified as a powerful strategy to overcome the limitations of traditional therapeutics to achieve satisfactory effects. However, various challenges related to the dosage form, delivery method, and, especially, application value, hampered the clinical transition of gene therapy. Here, aiming to regulate the cartilage inflammation and degeneration related abnormal IL-1β mRNA expression in osteoarthritis (OA), the interference oligonucleotides is integrated with the Au nanorods to fabricate the spherical nucleic acids (SNAs), to promote the stability and cell internalization efficiency. Furthermore, the complementary oligonucleotides are grafted onto hyaluronic acid (HA) to obtained DNA-grafted HA (DNAHA) for SNAs delivery by base pairing, resulting in significantly improved injectability and bio-stability of the system. After loading SNAs, the constructed DNAHA-SNAs system (HA-SNAs) performs a reversible NIR-triggered on-demand release of SNAs by photo-thermal induced DNA dehybridization and followed by post-NIR in situ hybridization. The in vitro and in vivo experiments showed that this system down-regulated catabolic proteases and up-regulated anabolic components in cartilage over extended periods of time, to safeguard the chondrocytes against degenerative changes and impede the continual advancement of OA.
6
Authors: Cachot, Amélie, et al
Published: Feb 2021
Authors: Cachot, Amélie, et al
Published: Feb 2021
CD4 T cells have been implicated in cancer immunity for their helper functions. Moreover, their direct cytotoxic potential has been shown in some patients with cancer. Here, by mining single-cell RNA-seq datasets, we identified CD4 T cell clusters displaying cytotoxic phenotypes in different human cancers, resembling CD8 T cell profiles. Using the peptide-MHCII-multimer technology, we confirmed ex vivo the presence of cytolytic tumor-specific CD4 T cells. We performed an integrated phenotypic and functional characterization of these cells, down to the single-cell level, through a high-throughput nanobiochip consisting of massive arrays of picowells and machine learning. We demonstrated a direct, contact-, and granzyme-dependent cytotoxic activity against tumors, with delayed kinetics compared to classical cytotoxic lymphocytes. Last, we found that this cytotoxic activity was in part dependent on SLAMF7. Agonistic engagement of SLAMF7 enhanced cytotoxicity of tumor-specific CD4 T cells, suggesting that targeting these cells might prove synergistic with other cancer immunotherapies.Fully functional, tumor-specific, SLAMF7-expressing cytotoxic CD4 T cells directly mediate immunity against human cancer.Fully functional, tumor-specific, SLAMF7-expressing cytotoxic CD4 T cells directly mediate immunity against human cancer.
5
From Paper: Chemically Engineered Immune Cell-Derived Microrobots and Biomimetic Nanoparticles: Emerging Biodiagnostic and Therapeutic Tools
From Paper: Chemically Engineered Immune Cell-Derived Microrobots and Biomimetic Nanoparticles: Emerging Biodiagnostic and Therapeutic Tools
Over the past decades, considerable attention has been dedicated to the exploitation of diverse immune cells as therapeutic and/or diagnostic cell-based microrobots for hard-to-treat disorders. To date, a plethora of therapeutics based on alive immune cells, surface-engineered immune cells, immunocytes’ cell membranes, leukocyte-derived extracellular vesicles or exosomes, and artificial immune cells have been investigated and a few have been introduced into the market. These systems take advantage of the unique characteristics and functions of immune cells, including their presence in circulating blood and various tissues, complex crosstalk properties, high affinity to different self and foreign markers, unique potential of their on-demand navigation and activity, production of a variety of chemokines/cytokines, as well as being cytotoxic in particular conditions. Here, the latest progress in the development of engineered therapeutics and diagnostics inspired by immune cells to ameliorate cancer, inflammatory conditions, autoimmune diseases, neurodegenerative disorders, cardiovascular complications, and infectious diseases is reviewed, and finally, the perspective for their clinical application is delineated.
5
From Paper: A perovskite retinomorphic sensor
Published: Dec 2020
From Paper: A perovskite retinomorphic sensor
Published: Dec 2020
Designed to outperform conventional computers when performing machine-learning tasks, neuromorphic computation is the principle whereby certain aspects of the human brain are replicated in hardware. While great progress has been made in this field in recent years, almost all input signals provided to neuromorphic processors are still designed for traditional (von Neumann) computer architectures. Here, we show that a simple photosensitive capacitor will inherently reproduce certain aspects of biological retinas. We found that capacitors based on metal halide perovskites will output a brief voltage spike in response to changes in incident light intensity, but output zero voltage under constant illumination. Such a sensor is not only optimized for use with spiking neuromorphic processors but also anticipated to have broad appeal from fields such as light detection and ranging, autonomous vehicles, facile recognition, navigation, and robotics.
16
From Paper: Science Journals — AAAS
Published: Dec 2020
From Paper: Science Journals — AAAS
Published: Dec 2020
We simulated materials on a supercomputer and discovered materials that have two or more interesting quantum properties. Having two quantum effects that coexist in the same material means that we can control one effect by manipulating the other, and vice-versa. That’s like having a soundboard installed directly in the material, with switches and knobs that we can play with to engineer its behavior and make new devices.
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From Paper: Bidirectional Correlations Between Dopaminergic Function and Motivation in Parkinson’s Disease
Published: Feb 2021
From Paper: Bidirectional Correlations Between Dopaminergic Function and Motivation in Parkinson’s Disease
Published: Feb 2021
Objective: To test the hypothesis that striatal dopamine function influences motivational alterations in Parkinson disease (PD), we compared vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DaT) imaging data in PD patients with impulse control disorders (ICDs), apathy, or neither. Methods: We extracted striatal binding ratios (SBR) from VMAT2 PET imaging ( 18 F-AV133) and DaTscans from the Parkinson’s Progression Markers Initiative (PPMI) multicenter observational study. Apathy and ICDs were assessed using the Movement Disorders Society-revised Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP), respectively. We used analysis of variance (ANOVA) and log-linear mixed-effects (LME) regression to model SBRs with neurobehavioral metrics. Results: Among 23 participants (mean age 62.7 years, mean disease duration 1.8 years) with VMAT2 imaging data, 5 had apathy, 5 had an ICD, and 13 had neither. ANOVA indicated strong groupwise differences in VMAT2 binding in right anterior putamen [F(2,20) = 16.2, p < 0.0001), right posterior putamen [F(2,20) = 16.9, p < 0.0001), and right caudate [F(2,20) = 6.8, p = 0.006)]. Post-hoc tests and repeated-measures analysis with LME regression also supported right striatal VMAT2 elevation in the ICD group and reduction in the apathy group relative to the group with neither ICD nor apathy. DaT did not exhibit similar correlations, but normalizing VMAT2 with DaT SBR strengthened bidirectional correlations with ICD (high VMAT2/DaT) and apathy (low VMAT2/DaT) in all striatal regions bilaterally. Conclusions: Our findings constitute preliminary evidence that striatal presynaptic dopaminergic function helps describe the neurobiological basis of motivational dysregulation in PD, from high in ICDs to low in apathy.
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