As a pandemic emerges, information on epidemic prevention disseminates among the populace, and the propagation of that information interacts with the proliferation of the disease. Mass media serve a ...pivotal function in facilitating the dissemination of epidemic-related information. Investigating coupled information-epidemic dynamics, while accounting for the promotional effect of mass media in information dissemination, is of significant practical relevance. Nonetheless, in the extant research, scholars predominantly employ an assumption that mass media broadcast to all individuals equally within the network: this assumption overlooks the practical constraint imposed by the substantial social resources required to accomplish such comprehensive promotion. In response, this study introduces a coupled information-epidemic spreading model with mass media that can selectively target and disseminate information to a specific proportion of high-degree nodes. We employed a microscopic Markov chain methodology to scrutinize our model, and we examined the influence of the various model parameters on the dynamic process. The findings of this study reveal that mass media broadcasts directed towards high-degree nodes within the information spreading layer can substantially reduce the infection density of the epidemic, and raise the spreading threshold of the epidemic. Additionally, as the mass media broadcast proportion increases, the suppression effect on the disease becomes stronger. Moreover, with a constant broadcast proportion, the suppression effect of mass media promotion on epidemic spreading within the model is more pronounced in a multiplex network with a negative interlayer degree correlation, compared to scenarios with positive or absent interlayer degree correlation.
Peptide self-assembly is a hierarchical process, often starting with the formation of α-helices, β-sheets or β-hairpins. However, how the secondary structures undergo further assembly to form ...higher-order architectures remains largely unexplored. The polar zipper originally proposed by Perutz is formed between neighboring β-strands of poly-glutamine via their side-chain hydrogen bonding and helps to stabilize the sheet. By rational design of short amphiphilic peptides and their self-assembly, here we demonstrate the formation of polar zippers between neighboring β-sheets rather than between β-strands within a sheet, which in turn intermesh the β-sheets into wide and flat ribbons. Such a super-secondary structural template based on well-defined hydrogen bonds could offer an agile route for the construction of distinctive nanostructures and nanomaterials beyond β-sheets.
Joint Remote State Preparation provides a useful way to securely transfer the known quantum states to the distant nodes. However, the limitation of resources often leads to the quantum channels ...constructed by distributed entangled pairs being incompatible with the transmitted states. In order to overcome this problem, a novel Joint Remote State Preparation protocol was proposed for transmitting general multi‐qudit states over quantum networks, providing a promising pathway to utilise the available Einstein‐Podolsky‐Rosen (EPR) channels with different levels. Several scenarios under noisy environments were discussed and some properties of the fidelity when transmitting the multi‐qudit state were demonstrated. It was demonstrated that both the prepared state and the kind of the noises could restrict the number of the participant nodes. Our scheme leverages the existing quantum resources, which addresses the issue of insufficient entanglement resources. This approach is easily adaptable to other quantum network structures, offering a potential solution for constructing a universal quantum network.
We propose a novel JRSP protocol for transmitting general multi‐qudit states over quantum networks, providing a promising pathway to utilize the available Einstein‐Podolsky‐Rosen (EPR) channels with different levels. Firstly, we investigate the joint remote state preparation scheme with the same‐level EPR pairs. Next, we generalize our scheme to the scenario where the prepared qudit states are incompatible with the EPR channels.
Human pluripotent stem cells (hPSCs) hold great promise for the treatment of various human diseases. However, their therapeutic benefits and mechanisms for treating corneal endothelial dysfunction ...remain undefined. Here, we developed a therapeutic regimen consisting of the combination of hPSC-derived corneal endothelial precursors (CEPs) with nicotinamide (NAM) for effective treatment of corneal endothelial dysfunction. In rabbit and nonhuman primate models, intracameral injection of CEPs and NAM achieved long-term recovery of corneal clarity and thickness, similar with the therapeutic outcome of cultured human corneal endothelial cells (CECs). The transplanted human CEPs exhibited structural and functional integration with host resident CECs. However, the long-term recovery relied on the stimulation of endogenous endothelial regeneration in rabbits, but predominantly on the replacing function of transplanted cells during the 3-year follow-up in nonhuman primates, which resemble human corneal endothelium with limited regenerative capacity. Mechanistically, NAM ensured in vivo proper maturation of transplanted CEPs into functional CECs by preventing premature senescence and endothelial-mesenchymal transition within the TGF-β-enriched aqueous humor. Together, we provide compelling experimental evidence and mechanistic insights of simultaneous delivery of CEPs and NAM as a potential approach for treating corneal endothelial dysfunction.
Monoclonal antibodies (mAbs) are an important class of biotherapeutics; as of 2020, dozens are commercialized medicines, over a hundred are in clinical trials, and many more are in preclinical ...developmental stages. Therapeutic mAbs are sequence modified from the wild type IgG isoforms to varying extents and can have different intrinsic structural stability. For chronic treatments in particular, high concentration (≥ 100 mg/mL) aqueous formulations are often preferred for at-home administration with a syringe-based device. MAbs, like any globular protein, are amphiphilic and readily adsorb to interfaces, potentially causing structural deformation and even unfolding. Desorption of structurally perturbed mAbs is often hypothesized to promote aggregation, potentially leading to the formation of subvisible particles and visible precipitates. Since mAbs are exposed to numerous interfaces during biomanufacturing, storage and administration, many studies have examined mAb adsorption to different interfaces under various mitigation strategies. This review examines recent published literature focusing on adsorption of bioengineered mAbs under well-defined solution and surface conditions. The focus of this review is on understanding adsorption features driven by distinct antibody domains and on recent advances in establishing model interfaces suitable for high resolution surface measurements. Our summary highlights the need to further understand the relationship between mAb interfacial adsorption and desorption, solution aggregation, and product instability during fill-finish, transport, storage and administration.
The corneal endothelium maintains corneal hydration through the barrier and pump function, while its dysfunction may cause corneal edema and vision reduction. Considering its development from neural ...crest cells (NCCs), here we investigated the efficacy of the human induced pluripotent stem cell (hiPSC)-derived NCCs for corneal endothelial regeneration in rabbits.
Directed differentiation of hiPSC-derived NCCs was achieved using the chemically defined medium containing GSK-3 inhibitor and TGF-β inhibitor. The differentiated cells were characterized by immunofluorescence staining, FACS analysis, and in vitro multi-lineage differentiation capacity. For in vivo functional evaluation, 1.0 × 10
hiPSC-derived NCCs or NIH-3 T3 fibroblasts (as control) combined with 100 μM Y-27632 were intracamerally injected into the anterior chamber of rabbits following removal of corneal endothelium. Rabbit corneal thickness and phenotype changes of the transplanted cells were examined at 7 and 14 days with handy pachymeter, dual-immunofluorescence staining, and quantitative RT-PCR.
The hiPSC-derived NCCs were differentiated homogenously through 7 days of induction and exhibited multi-lineage differentiation capacity into peripheral neurons, mesenchymal stem cells, and corneal keratocytes. After 7 days of intracameral injection in rabbit, the hiPSC-derived NCCs led to a gradual recovery of normal corneal thickness and clarity, when comparing to control rabbit with fibroblasts injection. However, the recovery efficacy after 14 days deteriorated and caused the reappearance of corneal edema. Mechanistically, the transplanted cells exhibited the impaired maturation, cellular senescence, and endothelial-mesenchymal transition (EnMT) after the early stage of the in vivo directional differentiation.
Transplantation of the hiPSC-derived NCCs rapidly restored rabbit corneal thickness and clarity. However, the long-term recovery efficacy was impaired by the improper maturation, senescence, and EnMT of the transplanted cells.
Eye is a complex organ with a highly specialized tissue structure. The establishment of human pluripotent stem cells (hPSCs) has allowed the simulation of eye development in vitro. Most ...differentiation works of hPSC-derived ocular cells focus on a single, tissue-specific lineage, however, that faces difficulty in reflecting the complexity of eye development. Recently, the generation of a self-formed ectodermal autonomous multi-zone of ocular cells availably mimics the process of whole-eye development. In this study, we developed a rapid defined method to induce the differentiation of multi-zone ocular cells (MZOCs) from human induced pluripotent stem cells, which specifically experienced the key progenitor stages of anterior neuroectoderm and eye field stem cells by a 2.5-dimensional culture. These differentiated cell types spanned neural retina, retinal pigment epithelium, surface ectoderm, and neural crest and lens cells. In addition, the surface ectoderm zone of MZOCs could be mechanically isolated and induced into corneal epithelial cells, and the isolated neural crest zone could be directed into corneal endothelial cells. This in vitro differentiation process vividly mimics the development of vertebrate eye, and it provides a promising model for the study of ocular morphogenesis, as well as an ideal resource of seed cells for corneal regenerative medicine.
Oxidative stress-induced retinal pigment epithelium (RPE) senescence is one of the important factors in the pathogenesis of age-related macular degeneration (AMD). This study aimed to develop a new ...antisenescence-based intervention and clarify its possible molecular mechanism.
A cell premature senescence model was established in both primary RPE cells and ARPE-19 cells by exposure of the cells to pulsed H₂O₂ stress for 5 days, and confirmed with senescence-associated β-galactosidase (SA-β-gal) staining. The final concentration of fullerenol (Fol) in the cell culture system was 5 μg/mL. Cellular redox status was determined by the examination of cellular reactive oxygen species (ROS) staining, catalase activity, and the ratio of reduced to oxidized glutathione, respectively. Deoxyribonucleic acid double-strand breaks were determined by quantitative analysis of γH₂AX. Cell cycle analysis was performed with flow cytometry. SIRT1 activity was examined with SIRT1 Assay Kit. SIRT1 overexpression and knockdown in ARPE-19 cells were performed with lentiviral-mediated infection.
Pulsed H₂O₂ exposure triggered the acetylation of p53 at lysine 382 (K382) and subsequent increase in its target p21(Waf1/Cip1). It also increased the number of accumulated phospho-γH2AX foci and the level of phosphor-ATM in RPE cells. Fullerenol protected the RPE cells, as it reduced the number of positive SA-β-gal-staining cells, alleviated the depletion of cellular antioxidants, and reduced genomic DNA damage. Its mechanism might involve the activation of deacetylase SIRT1, resulting in decreased levels of acetyl-p53 and p21(Waf1/Cip1). The roles of SIRT1 in protecting cells in response to Fol were further confirmed by applications of SIRT1 activator (resveratrol) and inhibitors (nicotinamide and sirtinol), and through SIRT1 overexpression and knockdown.
Fullerenol could rescue RPE cells from oxidative stress-induced senescence through its antioxidation activity and the activation of SIRT1. The protective effect of Fol is useful for the development of new strategies to treat oxidative stress-related retinal diseases like AMD.
Three ecotypes of rapeseed, winter, spring, and semi-winter, have been formed to enable the plant to adapt to different geographic areas. Although several major loci had been found to contribute to ...the flowering divergence, the genomic footprints and associated dynamic plant architecture in the vegetative growth stage underlying the ecotype divergence remain largely unknown in rapeseed. Here, a set of 41 dynamic i-traits and 30 growth-related traits were obtained by high-throughput phenotyping of 171 diverse rapeseed accessions. Large phenotypic variation and high broad-sense heritability were observed for these i-traits across all developmental stages. Of these, 19 i-traits were identified to contribute to the divergence of three ecotypes using random forest model of machine learning approach, and could serve as biomarkers to predict the ecotype. Furthermore, we analyzed genomic variations of the population, QTL information of all dynamic i-traits, and genomic basis of the ecotype differentiation. It was found that 213, 237, and 184 QTLs responsible for the differentiated i-traits overlapped with the signals of ecotype divergence between winter and spring, winter and semi-winter, and spring and semi-winter, respectively. Of which, there were four common divergent regions between winter and spring/semi-winter and the strongest divergent regions between spring and semi-winter were found to overlap with the dynamic QTLs responsible for the differentiated i-traits at multiple growth stages. Our study provides important insights into the divergence of plant architecture in the vegetative growth stage among the three ecotypes, which was contributed to by the genetic differentiation, and might contribute to environmental adaption and yield improvement.
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