We describe the epidemiology of a coronavirus disease (COVID-19) outbreak in a call center in South Korea. We obtained information on demographic characteristics by using standardized epidemiologic investigation forms. We performed descriptive analyses and reported the results as frequencies and proportions for categoric variables. Of 1,143 persons who were tested for COVID-19, a total of 97 (8.5%, 95% CI 7.0%–10.3%) had confirmed cases. Of these, 94 were working in an 11th-floor call center with 216 employees, translating to an attack rate of 43.5% (95% CI 36.9%–50.4%). The household secondary attack rate among symptomatic case-patients was 16.2% (95% CI 11.6%– 22.0%). Of the 97 persons with confirmed COVID-19, only 4 (1.9%) remained asymptomatic within 14 days of quarantine, and none of their household contacts acquired secondary infections. Extensive contact tracing, testing all contacts, and early quarantine blocked further transmission and might be effective for containing rapid outbreaks in crowded work settings.
Achieving spatiotemporal control of molecular self-assembly associated with actuation of biological functions inside living cells remains a challenge owing to the complexity of the cellular environments and the lack of characterization tools. We present, for the first time, the organelle-localized self-assembly of a peptide amphiphile as a powerful strategy for controlling cellular fate. A phenylalanine dipeptide (FF) with a mitochondria-targeting moiety, triphenyl phosphonium (Mito-FF), preferentially accumulates inside mitochondria and reaches the critical aggregation concentration to form a fibrous nanostructure, which is monitored by confocal laser scanning microscopy and transmission electron microscopy. The Mito-FF fibrils induce mitochondrial dysfunction via membrane disruption to cause apoptosis. The organelle-specific supramolecular system provides a new opportunity for therapeutics and in-depth investigations of cellular functions.
Nanostar and nanonetwork crystals were prepared from fully conjugated poly(3-(2-ethylhexyl)thiophene)-block-polythiophene (P3EHT-b-PT) via a simple INCP process. The structural conformation of the nanocrystals was investigated in detail, revealing that with an increase in the block length of PT, the morphology of the nanocrystals changed from nanospheres to nanorods, nanostars, and to nanonetworks.
Fasting and glucose shortage activate a metabolic switch that shifts more energy production to mitochondria. This metabolic adaptation ensures energy supply, but also elevates the risk of mitochondrial oxidative damage. Here, we present evidence that metabolically challenged mitochondria undergo active fusion to suppress oxidative stress. In response to glucose starvation, mitofusin 1 (MFN1) becomes associated with the protein deacetylase HDAC6. This interaction leads to MFN1 deacetylation and activation, promoting mitochondrial fusion. Deficiency in HDAC6 or MFN1 prevents mitochondrial fusion induced by glucose deprivation. Unexpectedly, failure to undergo fusion does not acutely affect mitochondrial adaptive energy production; instead, it causes excessive production of mitochondrial reactive oxygen species and oxidative damage, a defect suppressed by an acetylationresistant MFN1 mutant. In mice subjected to fasting, skeletal muscle mitochondria undergo dramatic fusion. Remarkably, fasting-induced mitochondrial fusion is abrogated in HDAC6-knockout mice, resulting in extensive mitochondrial degeneration. These findings show that adaptive mitochondrial fusion protects metabolically challenged mitochondria.
Pairs of ionic group dependence of the structure of a complex coacervate core micelle (C3M) in an aqueous solution was investigated using DLS, cryo-TEM, and SANS with a contrast matching technique and a detailed model analysis. Block copolyelectrolytes were prepared by introducing an ionic group (i.e., ammonium, guanidinium, carboxylate, and sulfonate) to poly(ethylene oxide-b-allyl glycidyl ether) (NPEO = 227 and NPAGE = 52), and C3Ms were formed by simple mixing of two oppositely-charged block copolyelectrolyte solutions with the exactly same degree of polymerization. All four C3Ms are spherical with narrow distribution of micelle dimension, and the cores are significantly swollen by water, resulting in relatively low brush density of PEO chains on the core surface. With the pair of strong polyelectrolytes, core radius and aggregation number increases, which reflects that the formation of complex coacervates are significantly sensitive to the pairs of ionic groups rather than simple charge pairing.
The design and synthesis of nanoparticles mimicking the key features in size, shape, and surface molecular organization of biological objects that provide danger‐signals are essential in the formulation of effective vaccine. Here, multifaceted immunomodulatory nanoliposomes (denoted as “tumosomes”) that can turn tumors into vaccines and induce enhanced antitumor immune response are suggested. Multifaceted tumosomes are synthesized by assembling tumor cell membrane proteins as tumor‐associated antigens with two lipid‐based adjuvants as pathogen characters (i.e., monophosphoryl lipid A as a danger signal, dimethyldioctadecylammonium as a cell‐invasion moiety). The enhanced antitumor immunity of tumosomes afforded by the improved antigenicity and antigen uptake efficiency is also evaluated in a tumor challenge experiment after their image‐guided intralymph node injection. Tumosomes are able to provide tumor antigens and molecular adjuvants for the priming of a long‐term adaptive immune response in tumor draining lymph nodes, as well as in the spleen. Tumosome injection leads to an inhibition of tumor growth, and the survival rate of mice treated with the tumosomes is higher than those of other groups. Taken together, the tumosomes are expected to be used for the reshaping the immune response in the lymph node and enhanced antitumor immunity.
Tailoring unique nanostructures of biocompatible and degradable polymers and the consequent elucidation of shape effects in drug delivery open tremendous opportunities not only to broaden their biomedical applications but also to identify new directions for the design of nanomedicine. Cellular organelles provide the basic structural and functional motif for the development of novel artificial nanoplatforms. Herein, aqueous onion‐like vesicles structurally mimicking multicompartmentalized cellular organelles by exhibiting exquisite control over the molecular assembly of poly(ethylene oxide)‐block‐poly(ε‐caprolactone) (PEO‐b‐PCL) semicrystalline amphiphiles are reported. Compared to in situ self‐assembly, emulsification‐induced assembly endows the resulting nanoaggregates of PEO‐b‐PCL with structural diversity such as helical ribbons and onion‐like vesicles through the molecular packing modification in the hydrophobic core with a reduction of inherent crystalline character of PCL. In particular, onion‐like vesicles composed of alternating walls and water channels are interpreted by nanometer‐scale 3D visualization via cryogenic‐electron tomography (cryo‐ET). Interestingly, the nature of the multi‐walled vesicles results in high drug‐loading capacity and stepwise drug release through hydrolytic cleavage of the PCL block. The crystalline arrangement of PCL at the molecular scale and the spatial organization of assembled structure at the nanoscale significantly affect the drug‐release behavior of PEO‐b‐PCL nanovehicles.
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