This study examined young children’s empathy towards interacted entity and none interacted agent, and whether the interaction or the appearance of the agent is more relevant on children’s the ...empathy, the entities include an interacted robot, a stuffed toy dog and a stone. Preschoolers (5-6 years of age, N=69) watched videos of three agents, including agent introducing cuts, agent struck by human hands cuts, agent placing in a box struck by human hands cuts. All of these three agents are non-living entities, an interacted robot dog with metal surface, a non-interacted stuffed toy dog (appearance alike a real dog), a stone. The preschoolers were required to ask a list of questions to obtain the data indicating their empathy towards each agent. The results revealed that the young children ascribe more anthropomorphism to robot dog relative to stuffed toy dog, while the empathy to both have no significance difference.
The adenine base editor (ABE), capable of catalyzing A•T to G•C conversions, is an important gene editing toolbox. Here, we systematically evaluate genome-wide off-target deamination by ABEs using ...the EndoV-seq platform we developed. EndoV-seq utilizes Endonuclease V to nick the inosine-containing DNA strand of genomic DNA deaminated by ABE in vitro. The treated DNA is then whole-genome sequenced to identify off-target sites. Of the eight gRNAs we tested with ABE, 2-19 (with an average of 8.0) off-target sites are found, significantly fewer than those found for canonical Cas9 nuclease (7-320, 160.7 on average). In vivo off-target deamination is further validated through target site deep sequencing. Moreover, we demonstrated that six different ABE-gRNA complexes could be examined in a single EndoV-seq assay. Our study presents the first detection method to evaluate genome-wide off-target effects of ABE, and reveals possible similarities and differences between ABE and canonical Cas9 nuclease.
β-Thalassemia is a global health issue, caused by mutations in the HBB gene. Among these mutations, HBB -28 （A〉G） mutations is one of the three most common mutations in China and Southeast Asia ...patients with β-thalassemia. Correcting this mutation in human embryos may prevent the disease being passed onto future generations and cure anemia. Here we report the first study using base editor （BE） system to correct disease mutant in human embryos. Firstly, we produced a 293T cell line with an exogenous HBB -28 （A〉G） mutant fragment for gRNAs and targeting efficiency evaluation. Then we collected primary skin fibroblast cells from a β-thalassemia patient with HBB -28 （A〉G） homozygous mutation. Data showed that base editor could precisely correct HBB -28 （A〉G） mutation in the patient＇s primary cells. To model homozygous mutation disease embryos, we consb＇ucted nuclear transfer embryos by fusing the lymphocyte or skin fibroblast cells with enucleated in vitro matured （IVM） oocytes.Notably, the gene correction efficiency was over 23.0% in these embryos by base editor. Although these embryos were still mosaic, the percentage of repaired blastomeres was over 20.0%. In addition, we found that base editor variants, with narrowed deamination window, could promote G-to-A conversion at HBB -28 site precisely in human embryos. Collectively, this study demonstrated the feasibility of curing genetic disease in human somatic cells and embryos by base editor system.
Genome editing tools such as the clustered regularly interspaced short palindromic repeat （CRISPR）-associated system （Cas） have been widely used to modify genes in model systems including animal ...zygotes and human cells, and hold tremendous promise for both basic research and clinical applications. To date, a serious knowledge gap remains in our understanding of DNA repair mechanisms in human early embryos, and in the efficiency and potential off-target effects of using technologies such as CRISPR/Cas9 in human pre-implantation embryos. In this report, we used tripronuclear （3PN） zygotes to further investigate CRISPR/Cas9-mediated gene editing in human cells. We found that CRISPR/Cas9 could effectively cleave the endogenous β-globin gene （HBB）. However, the efficiency of homologous recombination directed repair （HDR） of HBB was low and the edited embryos were mosaic. Off-target cleavage was also apparent in these 3PN zygotes as revealed by the T7E1 assay and whole-exome sequencing. Furthermore, the endogenous delta-globin gene （HBD）, which is homologous to HBB, competed with exogenous donor oligos to act as the repair template, leading to untoward mutations. Our data also indicated that repair of the HBB locus in these embryos occurred preferentially through the non-crossover HDR pathway. Taken together, our work highlights the pressing need to further improve the fidelity and specificity of the CRISPR/Cas9 platform, a prerequisite for any clinical applications of CRSIPR/Cas9-mediated editing.
Keloids are a type of fibrotic disease characterized by excessive collagen production and extracellular matrix (ECM) deposition. The symptoms of pain and itching and frequent recurrence after ...treatment significantly impact the quality of life and mental health of patients. A deeper understanding of the pathogenesis of keloids is crucial for the development of an effective therapeutic approach. Fibroblasts play a central role in the pathogenesis of keloids by producing large amounts of collagen fibers. Recent evidence indicates that keloids exhibit high immune cell infiltration, and these cells secrete cytokines or growth factors to support keloid fibroblast proliferation. This article provides an update on the knowledge regarding the keloid microenvironment based on recent single-cell sequencing literature. Many inflammatory cells gathered in keloid lesions, such as macrophages, mast cells, and T lymphocytes, indicate that keloids may be an inflammatory skin disease. In this review, we focus on the communication from immune cells to the fibroblasts and the potential of immunotherapy for keloids. We hope that this review will trigger interest in investigating keloids as an inflammatory disease, which may open up new avenues for drug development by targeting immune mediators.
Previous studies have estimated ground-level concentrations of particulate matter 2.5 (PM2.5) using satellite-derived aerosol optical depth (AOD) in conjunction with meteorological and land use ...variables. However, the impacts of urbanization on air pollution for predicting PM2.5 are seldom considered. Nighttime light (NTL) data, acquired with the Visible Infrared Imaging Radiometer Suite (VIIRS) aboard the Suomi National Polar-orbiting Partnership (S-NPP) satellite, could be useful for predictions because they have been shown to be good indicators of the urbanization and human activity that can affect PM2.5 concentrations. This study investigated the potential of incorporating VIIRS NTL data in statistical models for PM2.5 concentration predictions. We developed a mixed-effects model to derive daily estimations of surface PM2.5 levels in the Beijing–Tianjin–Hebei region using 3 km resolution satellite AOD and VIIRS NTL data. The results showed the addition of NTL information could improve the performance of the PM2.5 prediction model. The NTL data revealed additional details for predication results in areas with low PM2.5 concentrations and greater apparent seasonal variation due to the seasonal variability of human activity. Comparison showed prediction accuracy was improved more substantially for the model using NTL directly than for the model using the vegetation-adjusted NTL urban index that included NTL. Our findings indicate that VIIRS NTL data have potential for predicting PM2.5 and that they could constitute a useful supplemental data source for estimating ground-level PM2.5 distributions.
Lignocellulose nanofibers (LCNFs) as a new material is attracting extensive attention. The pretreatment and mechanical fibrillation are the two main stages involved in the preparation of LCNFs, and ...lignin plays the important role of these two stages. This review discussed the interaction between lignin and chemicals in the pretreatment stage, and discovered the general law of the effect of lignin in the mechanical fibrillation stage. Lignin exhibits both promotion and inhibition effects on mechanical fibrillation, and the mutual competition between the two effects ultimately affects the energy consumption, morphology and yield of LCNFs. Furthermore, the recent research progress related to the contributions of lignin on the functional application of LCNFs was summarized, aiming to provide profound guidance for the preparation and application of LCNFs.
Lignin plays important role in the preparation and functionalization of LCNFs, which shows both promotion and inhibition effect, like “Yang” and “Yin” in “Tai Chi”. The two effects counteract each other, jointly and case-dependently affect LCNFs. Display omitted
•Effects of lignin on the preparation and functionalization of LCNFs were reviewed.•Promotion and inhibition effect of lignin on mechanical fibrillation were summarized.•The contributions of lignin on the functional application of LCNFs were summarized.•The potential applications and challenges of LCNFs were proposed.
Recent advances in genome editing, especially CRISPR-Cas nucleases, have revolutionized both laboratory research and clinical therapeutics. CRISPR-Cas nucleases, together with the DNA damage repair ...pathway in cells, enable both genetic diversification by classical non-homologous end joining (c-NHEJ) and precise genome modification by homology-based repair (HBR). Genome editing in zygotes is a convenient way to edit the germline, paving the way for animal disease model generation, as well as human embryo genome editing therapy for some life-threatening and incurable diseases. HBR efficiency is highly dependent on the DNA donor that is utilized as a repair template. Here, we review recent progress in improving CRISPR-Cas nuclease-induced HBR in mammalian embryos by designing a suitable DNA donor. Moreover, we want to provide a guide for producing animal disease models and correcting genetic mutations through CRISPR-Cas nuclease-induced HBR in mammalian embryos. Finally, we discuss recent developments in precise genome-modification technology based on the CRISPR-Cas system.
Targeted point mutagenesis through homologous recombination has been widely used in genetic studies and holds considerable promise for repairing disease- causing mutations in patients. However, ...problems such as mosaicism and low mutagenesis efficiency continue to pose challenges to clinical applicaUon of such approaches. Recently, a base editor （BE） system built on cytidine （C） deaminase and CRISPR/Cas9 technology was developed as an alternative method for targeted point mutagenesis in plant, yeast, and human cells. Base editors convert C in the deamination window to thymidine （T） efficiently, however, it remains unclear whether targeted base editing in mouse embryos is feasible. In this report, we generated a modified high- fidelity version of base editor 2 （HF2-BE2）, and investigated its base editing efficacy in mouse embryos. We found that HF2-BE2 could convert C to T efficiently, with up to 100% biallelic mutation efficiency in mouse embryos. Unlike BE3, HF2-BE2 could convert C to T on both the target and non-target strand, expanding the editing scope of base editors. Surprisingly, we found HF2-BE2 could also deaminate C that was proximal to the gRNA-binding region. Taken together, our work demonstrates the feasibility of generating point mutations in mouse by base editing, and underscores the need to carefully optimize base editing systems in order to eliminate proximal-site deamination.
Abstract Non-optimal temperatures significantly influence public health. However, the role of socio-economic factors in modulating health risks associated with non-optimal temperatures varies ...geographically and among different populations. Thus, the meteorological, air quality, health data, and socio-economic indicators were obtained from 23 districts in North and 48 districts in East China, respectively. Employing a two-stage meta-analysis, the exposure-response relationship was constructed for temperature against mortality from non-accidental causes, cardiovascular and cerebrovascular diseases, and respiratory illnesses. Furthermore, a non-linear spline regression was applied to assess the impact of socio-economic indicators on the exposure-response relationship and predicted future risks under various Shared Socioeconomic Pathways. The results revealed that the influence of socio-economic factors on the exposure-response curve showed heterogeneity in East China and North China. In North China, the shape of the exposure-response curve changed greatly under different socio-economic levels, while it remained similar in East China. In East China, the relative risk of heat and cold exposure was reduced in regions with high GDP, high levels of public finance, good medical services, and a low proportion of the elderly population. Specifically, the risk of non-accidental deaths due to heat shows a nearly linear negative correlation with per capita GDP in East China, with a decrease of the relative risk by 0.075 for every 10 thousand yuan increase in per capita GDP. Future projections indicate that population aging plays a decisive role in shaping the exposure-response curves. Although economic growth can reduce the risk of heat-related mortality, the combined effect of population aging and economic increase results in steeper exposure-response curves in both hot and cold temperature ranges in the future. In conclusion, although spatial variations in relative risk changes still exist, enhancing the adaptive capacity of populations can mitigate health risks associated with future climate change.
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