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Humanity is experiencing a catastrophic pandemic. SARS-CoV-2 has spread globally to cause significant morbidity and mortality, and there still remain unknowns about the biology and pathology of the virus. Even with testing, tracing, and social distancing, many countries are struggling to contain SARS-CoV-2. COVID-19 will only be suppressible when herd immunity develops, either because of an effective vaccine or if the population has been infected and is resistant to reinfection. There is virtually no chance of a return to pre-COVID-19 societal behavior until there is an effective vaccine. Concerted efforts by physicians, academic laboratories, and companies around the world have improved detection and treatment and made promising early steps, developing many vaccine candidates at a pace that has been unmatched for prior diseases. As of August 11, 2020, 28 of these companies have advanced into clinical trials with Moderna, CanSino, the University of Oxford, BioNTech, Sinovac, Sinopharm, Anhui Zhifei Longcom, Inovio, Novavax, Vaxine, Zydus Cadila, Institute of Medical Biology, and the Gamaleya Research Institute having moved beyond their initial safety and immunogenicity studies. This review analyzes these frontrunners in the vaccine development space and delves into their posted results while highlighting the role of the nanotechnologies applied by all the vaccine developers.An inverse-electron-demand Diels-Alder (IEDDA) reaction using genetically encoded tetrazine variants enables rapid bioconjugation for diverse applications in vitro and in cellulo. However, in vivo bioconjugation using genetically encoded tetrazine variants is challenging, because the IEDDA coupling reaction competes with rapid elimination of reaction partners in vivo. Here, we tested the hypothesis that a genetically encoded phenylalanine analogue containing a hydrogen-substituted tetrazine (frTet) would increase the IEDDA reaction rate, thereby allowing for successful bioconjugation in vivo. We found that the in vitro IEDDA reaction rate of superfolder green fluorescent protein (sfGFP) containing frTet (sfGFP-frTet) was 12-fold greater than that of sfGFP containing methyl-substituted tetrazine (sfGFP-Tet_v2.0). Additionally, sfGFP variants encapsulated with chitosan-modified, pluronic-based nanocarriers were delivered into nude mice or tumor-bearing mice for in vivo imaging. The in vivo-delivered sfGFP-frTet exhibited almost complete fluorescence recovery upon addition of trans-cyclooctene via the IEDDA reaction within 2 h, whereas sfGFP-Tet_v2.0 did not show substantial fluorescence recovery. These results demonstrated that the genetically encoded frTet allows an almost complete IEDDA reaction in vivo upon addition of trans-cyclooctene, enabling temporal control of in vivo bioconjugation in a very high yield.Garcinol is a natural product from the Garcinia Indica fruit and is well-known as an antioxidant, anti-inflammatory, and anticancer agent. However, the understanding of its mechanism of action is still incomplete. It has been reported to be a histone acetyltransferase (HAT) inhibitor. Here, we surprisingly found that garcinol is a potent histone deacetylase 11 (HDAC11) inhibitor (IC50 ∼ 5 μM in vitro with the HPLC assay and IC50 ∼ 10 μM in the cellular SHMT2 fatty acylation assay), which is comparable to previously reported HDAC11 inhibitors. Additionally, among all the HDACs tested, garcinol specifically inhibits HDAC11 over other HDACs. HDAC11 is the only class IV HDAC, and there are very few inhibitors available for it. https://www.selleckchem.com/products/unc-3230.html Therefore, this study provides a new HDAC11 inhibitor lead from natural products and may help explain the various biological activities of garcinol.Cell therapy and cellular engineering begin with internalizing synthetic biomolecules and functional nanomaterials into primary cells. Conventionally, electroporation, lipofection, or viral transduction has been used; however, these are limited by their cytotoxicity, low scalability, cost, and/or preparation complexity, especially in primary cells. Thus, a universal intracellular delivery method that outperforms the existing methods must be established. Here, we present a versatile intracellular delivery platform that leverages intrinsic inertial flow developed in a T-junction microchannel with a cavity. The elongational recirculating flows exerted in the channel substantially stretch the cells, creating discontinuities on cell membranes, thereby enabling highly effective internalization of nanomaterials, such as plasmid DNA (7.9 kbp), mRNA, siRNA, quantum dots, and large nanoparticles (300 nm), into different cell types, including hard-to-transfect primary stem and immune cells. We identified that the internalization mechanism of external cargos during the cell elongation-restoration process is achieved by both passive diffusion and convection-based rapid solution exchange across the cell membrane. Using fluidic cell mechanoporation, we demonstrated a transfection yield superior to that of other state-of-the-art microfluidic platforms as well as current benchtop techniques, including lipofectamine and electroporation. In summary, the intracellular delivery platform developed in the present study enables a high delivery efficiency (up to 98%), easy operation (single-step), low material cost ( less then $1), high scalability (1 × 106 cells/min), minimal cell perturbation (up to 90%), and cell type/cargo insensitive delivery, providing a practical and robust approach anticipated to critically impact cell-based research.Time-of-flight secondary ion mass spectrometry (TOF-SIMS) imaging provides molecular speciation at the micrometer scale, while the penetration depth of the primary ion beam is limited to the top-layers of a sample. These combined properties make TOF-SIMS potentially an ideal technique to study oil-gas interfaces. TOF-SIMS spectra of three crude oils were evaluated, and only low-mass fragment ions could be assigned to molecular structures unambiguously. Films of crude oils were incubated under air, oil vapor, or water vapor for various times. TOF-SIMS images of a polar crude oil revealed feeble structures of ∼10 μm large round patches that grew to ∼30 μm large crystals when incubated under air and oil vapor, respectively. Principal component analysis of the images showed that the continuous phase had typical aromatic signatures, while the patches and crystals had alkane-like characteristics. No features showed up when the oil film was incubated under water vapor, which indicated that saturated water vapor prevented the accumulation of nonpolar alkane-like compounds at the oil-gas interface.
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