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Leukocyte cell-derived chemotaxin 2 (LECT2) is a multifunctional cytokine that especially plays an important role in innate immune. However, the roles of LECT2 in the immune response of the economically important fish Nile tilapia ( Oreochromis niloticus ) against bacterial infection remains unclear. In this study, a lect2 gene from Nile tilapia ( On-lect2 ) was identified, and its roles in the fish’s immune response against bacterial infection were determined and characterised. On-lect2 contains an open reading frame of 456 bp that encodes a peptide of 151 amino acids, as well as the conservative peptidase M23 domain. On-LECT2 is 62%–84% identical to other fish species and about 50% identical to mammals. The highest transcriptional level of On-lect2 was detected in the liver, whereas the lowest levels were detected in the other tissues. Moreover, the On-LECT2 protein is located mainly in the brain and head kidney. The transcriptional levels of On-lect2 substantially increased in the head kidney, brain, liver and spleen after Streptococcus agalactiae infection. Knockdown On-lect2 led to higher mortality due to liver necrosis or haemorrhage and splenomegaly. In vitro analysis indicated that the recombinant protein of On-LECT2 improved phagocytic activity of head kidney-derived macrophages. In vivo challenge experiments revealed several functions of On-LECT2 in the immune response of Nile tilapia against bacterial infection, including promotion of inflammation, reduction of tissue damages and improvement of survival rate.

Low-visibility maritime image enhancement is essential for maritime surveillance in extreme weathers. However, traditional methods merely optimize contrast while ignoring image features and color recovery, which leads to subpar enhancement outcomes. The majority of learning-based methods attempt to improve low-visibility images by only using local features extracted from convolutional layers, which significantly improves performance but still falls short of fully resolving these issues. Furthermore, the computational complexity is always sacrificed for larger receptive fields and better enhancement in CNN-based methods. In this paper, we propose a multiple-feature fusion-guided low-visibility enhancement network (MFF-Net) for real-time maritime surveillance, which extracts global and local features simultaneously to guide the reconstruction of the low-visibility image. The quantitative and visual experiments on both standard and maritime-related datasets demonstrate that our MFF-Net provides superior enhancement with noise reduction and color restoration, and has a fast computational speed. Furthermore, the object detection experiment indicates practical benefits for maritime surveillance.

The contact between two rough surfaces is essentially the contact between micro-bulge of different shapes. In the process of interference fit, the distribution of contact area and contact stress at different positions of the two rough contact surfaces is uneven. In this paper, based on the test results of the morphology of machined surfaces with different surface roughness, a two-dimensional curve model of the contact surface is established according to the W-M fractal function and Matlab software. The contact area and contact load are analyzed with a two-dimensional finite element contact model of the double rough surface that established with Abaqus software. And the effect of surface roughness and surface displacement on the contact area and contact load is analyzed with the finite element contact model.

A statistics method is proposed to research the quantitative correlation between device performance and structure parameters fluctuation of avalanche photodiode (APD), through theoretical simulation and setting varied structure parameters. The characteristics of InGaAsP/InP APD and InGaAs/InP APD with the same primary structure parameters are discussed, and the quantitative correlation between excess bias fluctuation and structure parameters fluctuation of the two species APDs is concluded. It is revealed that the excess bias of APD is strongly determined by the doping of charge layer, the width of charge layer and multiplication layer, and it is slightly determined by the doping and the width of absorption layer. Moreover, the two species APDs have close response uniformity and technical stability at the same condition of material manufacture and device process.

The comorbidity rate of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) is high; nevertheless, the reasons behind this high rate remain unclear. Their similar genetic makeup probably contributes to this comorbidity. Based on data obtained from the genome-wide association study of IBD and RA, we first assessed an overall genetic association by performing the linkage disequilibrium score regression (LDSC) analysis. Further, a local correlation analysis was performed by estimating the heritability in summary statistics. Next, the causality between the two diseases was analyzed by two-sample Mendelian randomization (MR). A genetic overlap was analyzed by the conditional/conjoint false discovery rate (cond/conjFDR) method.LDSC with specific expression of gene analysis was performed to identify related tissues between the two diseases. Finally, GWAS multi-trait analysis (MTAG) was also carried out. IBD and RA are correlated at the genomic level, both overall and locally. The MR results suggested that IBD induced RA. We identified 20 shared loci between IBD and RA on the basis of a conjFDR of <0.01. Additionally, we identified two tissues, namely spleen and small intestine terminal ileum, which were commonly associated with both IBD and RA. Herein, we proved the presence of a polygenic overlap between the genetic makeup of IBD and RA and provided new insights into the genetic architecture and mechanisms underlying the high comorbidity between these two diseases.

Mutations in a tubulin gene caused infertility due to oocyte arrest in about a third of families tested. The investigators found that the mutant tubulins wreak havoc on microtubule assembly in the oocyte. Successful human reproduction starts when a metaphase II oocyte fuses with a sperm cell to form a fertilized egg. In human oocytes, the meiotic cell cycle begins in the neonatal ovary and pauses at prophase I of meiosis until puberty, when a surge of luteinizing hormone stimulates the resumption of meiosis and ovulation. This leads to progression of the oocyte from metaphase I to metaphase II. 1 – 3 Oocytes arrested in prophase I have an intact nucleus, termed the germinal vesicle, whereas oocytes that have resumed meiosis are characterized by the breakdown of the germinal vesicle. After germinal-vesicle breakdown, metaphase I . . .

Background Gene knock‐in (KI) in animal cells via homology‐directed repair (HDR) is an inefficient process, requiring a laborious work for screening from few modified cells. HDR tends to occur in the S and G2/M phases of cell cycle; therefore, strategies that enhance the proportion of cells in these specific phases could improve HDR efficiency. Results We used various types of cell cycle inhibitors to synchronize the cell cycle in S and G2/M phases in order to investigate their effect on regulating CRISPR/Cas9-mediated HDR. Our results indicated that the four small molecules—docetaxel, irinotecan, nocodazole and mitomycin C—promoted CRISPR/Cas9-mediated KI with different homologous donor types in various animal cells. Moreover, the small molecule inhibitors enhanced KI in animal embryos. Molecular analysis identified common signal pathways activated during crosstalk between cell cycle and DNA repair. Synchronization of the cell cycle in the S and G2/M phases results in CDK1/CCNB1 protein accumulation, which can initiate the HDR process by activating HDR factors to facilitate effective end resection of CRISPR-cleaved double-strand breaks. We have demonstrated that augmenting protein levels of factors associated with the cell cycle via overexpression can facilitate KI in animal cells, consistent with the effect of small molecules. Conclusion Small molecules that induce cell cycle synchronization in S and G2/M phases promote CRISPR/Cas9-mediated HDR efficiency in animal cells and embryos. Our research reveals the common molecular mechanisms that bridge cell cycle progression and HDR activity, which will inform further work to use HDR as an effective tool for preparing genetically modified animals or for gene therapy.

Urban green space accessibility is an essential consideration in determining environmental liveability and the well-being of individuals, and the spatial inequity of urban green space supply and demand has become a research focus. However, few studies have conducted a multidimensional and comprehensive assessment of the influences on accessibility from the different perspectives of supply and demand. To address this, our study centred on the mountainous Chongqing region and established a comprehensive research framework examining the spatial pattern of accessibility of urban green spaces and its correlation with physical geographical elements and socioeconomic factors. We reveal the spatial distribution characteristics of urban green space accessibility by using Gaussian-based two-step floating catchment area and network analysis methods and further observe the spatial clustering features utilising hotspot analysis. The ordinary least squares (OLS) model and the spatial lag model were used to evaluate the physical geographical and socioeconomic disparities. Our findings reveal explicit blind spots in urban green space accessibility, primarily within the 30 min travel threshold in the city’s marginal area. A discernible supply–demand imbalance existed in the urban core, constituted by implicit blind spots. Furthermore, we identified that the relationship between urban green space accessibility and elevation under different methods is not always consistently significant over space because spatial heterogeneity may exist. Most concerningly, the study found inequities in urban green space accessibility, particularly impacting vulnerable demographics such as the elderly and lower-income groups. These results can inform urban planners and policymakers about the blind spots of urban green space accessibility and sufficiently consider the physical and socioeconomic heterogeneity of the space to determine where and how to implement inclusive urban greening policies or planning schemes. It is also of great significance in increasing awareness of vulnerable groups and preventing environmental inequality.

The engineered TadA variants used in cytosine base editors (CBEs) present distinctive advantages, including a smaller size and fewer off-target effects compared to cytosine base editors that rely on natural deaminases. However, the current TadA variants demonstrate a preference for base editing in DNA with specific motif sequences and possess dual deaminase activity, acting on both cytosine and adenosine in adjacent positions, limiting their application scope. To address these issues, we employ TadA orthologs screening and multi sequence alignment (MSA)-guided protein engineering techniques to create a highly effective cytosine base editor (aTdCBE) without motif and adenosine deaminase activity limitations. Notably, the delivery of aTdCBE to a humanized mouse model of Duchenne muscular dystrophy (DMD) mice achieves robust exon 55 skipping and restoration of dystrophin expression. Our advancement in engineering TadA ortholog for cytosine editing enriches the base editing toolkits for gene-editing therapy and other potential applications. Engineered TadA variants in cytosine base editors (CBEs) offer advantages like smaller size and reduced off-target effects. Here, authors develop an advanced CBE (aTdCBE) through ortholog screening and protein engineering, successfully enabling exon skipping in Duchenne muscular dystrophy model.