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Stroke remains one of the leading causes of adult disability worldwide, with neovascularization is crucial for brain repair after stroke. However, neutrophil infiltration hinders effective neovascularization, necessitating timely clearance by microglia through phagocytosis. Unfortunately, microglial phagocytic function is often impaired by metabolic defects, hindering post-stroke recovery. Ginsenoside Rg1, derived from Panax ginseng, exhibits neuroprotective properties and regulates cellular metabolism in vitro but its therapeutic application is limited by poor brain penetration. Here, we present a targeted delivery system utilizing neutrophil-like cell membrane vesicles (NCM), prepared via nitrogen cavitation, to enhance Rg1 delivery to the brain. These biomimetic vesicles exploit the inherent targeting ability of neutrophil membranes to reach brain injury sites and are subsequently taken up by microglia. Our findings demonstrate that Rg1-loaded vesicles enhance microglial clearance of neutrophils, reduce neutrophil extracellular traps release, and mitigate tissue damage. These effects improve the post-stroke microenvironment, promote vascular remodeling, and ultimately contribute to functional recovery. This strategy highlights the potential of targeted reprogramming microglial cells to enhance their endogenous repair capabilities, offering a promising therapeutic avenue for ischemic stroke management.

Abstract [Objective] The study aims to investigate the differential efficacy of anti-leaf spot in barley (Hordeum vulgare L.) of various concentrations of exogenous methyl jasmonate (MeJA) and understand the underlying mechanisms, thereby providing a foundation for the application of MeJA in controlling barley leaf spot. [Methods] We used ‘Mengpimai 3’ (MP3) seedlings as materials and conducted three different treatments: Inoculating the barley leaves with sterile water without any Bipolaris sorokiniana (the causal agent of the disease), inoculating the barley leaves with sterile water after treatment, and treating the barley leaves with different concentrations (0.5, 1.0, 1.5, 2.0, 2.5 mmol/L) of methyl jasmonate (MeJA) before inoculation with the pathogen. The disease incidence was investigated at the three-leaf stage based on disease index to determine the optimal MeJA concentration. We measured antioxidant enzyme activities, anti-disease-related enzyme activities, malondialdehyde, proline, soluble sugar, and soluble protein contents, and the expression levels of related genes under no inoculating treatment, inoculation treatment, and inoculating + optimal MeJA concentration treatment. [Results] (1) Exogenous application of MeJA enhanced MP3 resistance against spot blotch, particularly at 1.5 mmol/L where there was a significant reduction of 19.03% (P

The utilization of deep learning algorithms for side-scan sonar target detection is impeded by the restricted quantity and representativeness of side-scan sonar (SSS) samples. To address this issue, this paper proposes a method for image augmentation using a CC-WGAN network. First, the generator incorporates the Convolutional Block Attention Module (CBAM) to enhance the assimilation of global information and local features in the input images. This integration also improves stability and avoids mode collapse problems associated with the original Generative Adversarial Network. Subsequently, the CBAM is incorporated into the discriminator to facilitate a better understanding of the relevance and significance of input data, thereby enhancing the model’s generalization ability. Finally, based on this model, existing few-sample SSS images are augmented, and we utilize the augmented images for discrimination and detection with YOLOv5. The experimental results show that following training with the SSS dataset that is augmented by this network, the accuracy of target detection increased by 7.6%, validating the feasibility of our proposed method. This method presents a novel solution to the problem of low model accuracy in underwater target detection with side-scan sonar due to limited samples.

Abstract The role of gut microbiota in modulating the durability of COVID-19 vaccine immunity is yet to be characterised. In this cohort study, we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline, 1 month, and 6 months post vaccination (p.v.). Neutralisation antibody, plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition. A significantly higher level of neutralising antibody (at 6 months p.v.) was found in BNT162b2 vaccinees who had higher relative abundances of Bifidobacterium adolescentis, Bifidobacterium bifidum, and Roseburia faecis as well as higher concentrations of nicotinic acid (Vitamin B) and γ-Aminobutyric acid (P

Spermatogenesis is regulated by genetic and epigenetic factors. However, the genes and signaling pathways mediating human spermatogenesis remain largely unknown. Here, we have for the first time explored the expression, function, and mechanism of glutathione peroxidase 3 (GPx3) in controlling the proliferation and apoptosis of human spermatogonial stem cells (SSCs). We found that GPx3 was expressed in human SSCs. Notably, we revealed that GPx3 knockdown resulted in the decrease in the proliferation, DNA synthesis, and cyclin B1 level in human SSC lines, which possessed the phenotypic features of human primary SSCs. Flow cytometry and TUNEL assays showed that GPx3 silencing led to enhancement of early apoptosis of human SSC line. RNA sequencing was utilized to identify CXCL10 as a target of GPx3 in human SSCs, and notably, both double immunostaining and co-immunoprecipitation (co-IP) demonstrated that there was an association between GPx3 and CXCL10 in these cells. CXCL10-shRNA resulted in the reduction in the proliferation and DNA synthesis of human SSC line and an increase in apoptosis of these cells. Taken together, these results implicate that GPx3 regulates the proliferation, DNA synthesis, and early apoptosis of human SSC line via mediating CXCL10 and cyclin B1. This study, thus, offers a novel insight into the molecular mechanism regulating the fate determinations of human SSCs and human spermatogenesis.

Low back pain is one of the most serious public health problems worldwide and the major clinical manifestation of intervertebral disc degeneration (IVDD). The key pathological change during IVDD is dysfunction of the annulus fibrosus (AF). However, due to the lack of an in-depth understanding of AF biology, the methods to reconstruct the AF are very limited. In this study, the mice AF cell atlas were decoded by single-cell RNA sequencing to provide a guide for AF reconstruction. The results first identify a new population of AF cells, fibrochondrocyte-like AF cells, which synthesize both collagen I and collagen II and are potential functional cells for AF reconstruction. According to the dual features of the AF extracellular matrix, a composite hydrogel based on the acylation of methacrylated silk fibroin with methacrylated hyaluronic acid was produced. To obtain the ability to stimulate differentiation, the composite hydrogels were combined with a fibrochondrocyte-inducing supplement. Finally, reconstruction of the AF defects, by the novel AF stem cell-loaded composite hydrogel, could be observed, its amount of chondroid matrices recovered to 31.7% of AF aera which is significantly higher than that in other control groups. In summary, this study decodes the AF cell atlas, based on which a novel strategy for AF reconstruction is proposed.

The Wuyi Mountains in China are one of the largest and most complete subtropical forest ecosystems at the same latitude in the world. However, our limited understanding of the function of this distinctive ecosystem means that the interrelationship between species diversity and ecosystem functioning needs to be investigated if evergreen broadleaf forests (EBLFs) are to be protected. Here, we calculated species richness, the Shannon–Wiener index, and the Pielou index in large-, medium-, and small-scale (20 m × 20 m, 10 m × 10 m, and 5 m × 5 m) forest dynamics plots (FDPs). We also investigated the interrelationships between species diversity and aboveground biomass (AGB)/productivity in FDPs at the different scales using the generalized linear regression model. The results showed that species diversity and AGB positively interrelated with each other, whereas there was no species diversity-productivity interrelationship in the subtropical BLF on the Wuyi Mountains. The structural equation model (SEM) showed that elevation was a key factor directly affecting AGB. These findings lead to the conclusion that productivity is not solely correlated with species diversity and that abiotic factors probably mediate the positive interrelationship between species diversity and ecosystem functioning. This study provides theoretical basis that can be used to protect EBLFs in subtropical areas and the results can be used to improve the construction of artificial forest communities and vegetation restoration at the same latitude.

The gut microbiome is hypothesized to play a crucial role in the development of obesity and insulin resistance (IR); the pathways linking the microbiome to IR in pediatrics have yet to be precisely characterized. We aimed to determine the relationship between the gut microbiome composition and metabolic functions and IR in children with obesity. In a cross-sectional study, fecal samples from children with obesity (10–16 years old) were collected for taxonomical and functional analysis of the fecal microbiome using shotgun metagenomics. The homeostatic model assessment for insulin resistance (HOMA-IR) was determined using fasting glucose and insulin. Associations between HOMA-IR and α-diversity measures as well as metabolic pathways were evaluated using Spearman correlations; relationships between HOMA-IR and β-diversity were assessed by permutational multivariate analysis of variance. Twenty-one children (nine males; median: age = 12.0 years; BMI z-score = 2.9; HOMA-IR = 3.6) completed the study. HOMA-IR was significantly associated with measures of α-diversity but not with β-diversity. Children with higher HOMA-IR exhibited lower overall species richness, Firmicutes species richness, and overall Proteobacteria species Shannon diversity. Furthermore, HOMA-IR was inversely correlated with the abundance of pathways related to the biosynthesis of lipopolysaccharides, amino acids, and short-chain fatty acids, whereas positive correlations between HOMA-IR and the peptidoglycan biosynthesis pathways were observed. In conclusion, insulin resistance was associated with decreased microbial α-diversity measures and abundance of genes related to the metabolic pathways. Our study provides a framework for understanding the microbial alterations in pediatric obesity.

Early intervention with fecal microbiota transplantation (FMT) improves the growth performance and intestinal barrier function of piglets. Accelerating intestinal oxygen concentration is beneficial for symbiotic bacterial colonization. Saccharomyces boulardii (SB) is an aerobic fungus, which may contribute to the colonization of anaerobic symbiotic bacteria by competing for oxygen. Clostridium butyricum (CB) improves intestinal barrier function and performance, via regulating the gut microbiota composition of piglets. The objective of this study was to investigate the effect of early intervention with FMT combining CB and SB on growth performance, diarrhea, and intestinal barrier function in piglets. A total of 77 litters of neonatal piglets assigned to one of six treatments, which treated with antibiotics (AB), placebo (CON), and FMT (FMT), FMT-added CB (FMT+C), FMT-added SB (FMT+S), and FMT-added CB and SB (FMT+C+S), respectively. FMT+C+S treated piglets had higher body weight (BW) and average daily gain (ADG) both in weaning and finial period, and it significantly increased the levels of fecal mucin-2 (MUC2), fecal short-chain fatty acids (SCFAs), and relative abundance of fecal Lactobacillus spp., and Bifidobacterium genus. Moreover, early intervention with FMT+C+S reduced the diarrhea rate during the experiment. FMT+C+S also decreased the level of plasma diamine oxidase (DAO) and D-lactate (D-LA), and relative abundance of fecal E. coli during the suckling period. In summary, early intervention with FMT combining CB and SB improved the growth performance, intestinal barrier function, fecal SCFAs concentration, and fecal Lactobacillus and Bifidobacterium of piglets.

Abstract Background Synthetic lethality experiments identify pairs of genes with complementary function. More direct functional associations (for example greater probability of membership in a single protein complex) may be inferred between genes that share synthetic lethal interaction partners than genes that are directly synthetic lethal. Probabilistic algorithms that identify gene modules based on motif discovery are highly appropriate for the analysis of synthetic lethal genetic interaction data and have great potential in integrative analysis of heterogeneous datasets. Results We have developed Genetic Interaction Motif Finding (GIMF), an algorithm for unsupervised motif discovery from synthetic lethal interaction data. Interaction motifs are characterized by position weight matrices and optimized through expectation maximization. Given a seed gene, GIMF performs a nonlinear transform on the input genetic interaction data and automatically assigns genes to the motif or non-motif category. We demonstrate the capacity to extract known and novel pathways for Saccharomyces cerevisiae (budding yeast). Annotations suggested for several uncharacterized genes are supported by recent experimental evidence. GIMF is efficient in computation, requires no training and automatically down-weights promiscuous genes with high degrees. Conclusion GIMF effectively identifies pathways from synthetic lethality data with several unique features. It is mostly suitable for building gene modules around seed genes. Optimal choice of one single model parameter allows construction of gene networks with different levels of confidence. The impact of hub genes the generic probabilistic framework of GIMF may be used to group other types of biological entities such as proteins based on stochastic motifs. Analysis of the strongest motifs discovered by the algorithm indicates that synthetic lethal interactions are depleted between genes within a motif, suggesting that synthetic lethality occurs between-pathway rather than within-pathway.

Abstract Background In a genetic interaction, the phenotype of a double mutant differs from the combined phenotypes of the underlying single mutants. When the single mutants have no growth defect, but the double mutant is lethal or exhibits slow growth, the interaction is termed synthetic lethality or synthetic fitness. These genetic interactions reveal gene redundancy and compensating pathways. Recently available large-scale data sets of genetic interactions and protein interactions in Saccharomyces cerevisiae provide a unique opportunity to elucidate the topological structure of biological pathways and how genes function in these pathways. Results We have defined congruent genes as pairs of genes with similar sets of genetic interaction partners and constructed a genetic congruence network by linking congruent genes. By comparing path lengths in three types of networks (genetic interaction, genetic congruence, and protein interaction), we discovered that high genetic congruence not only exhibits correlation with direct protein interaction linkage but also exhibits commensurate distance with the protein interaction network. However, consistent distances were not observed between genetic and protein interaction networks. We also demonstrated that congruence and protein networks are enriched with motifs that indicate network transitivity, while the genetic network has both transitive (triangle) and intransitive (square) types of motifs. These results suggest that robustness of yeast cells to gene deletions is due in part to two complementary pathways (square motif) or three complementary pathways, any two of which are required for viability (triangle motif). Conclusion Genetic congruence is superior to genetic interaction in prediction of protein interactions and function associations. Genetically interacting pairs usually belong to parallel compensatory pathways, which can generate transitive motifs (any two of three pathways needed) or intransitive motifs (either of two pathways needed).