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In response to the global threat posed by bacterial pathogens, which are the second leading cause of death worldwide, vaccine development is challenged by the diversity of bacterial serotypes and the lack of immunoprotection across serotypes. To address this, we introduce BacScan, a novel genome-wide technology for the rapid discovery of conserved highly immunogenic proteins (HIPs) across serotypes. Using bacterial-specific serum, BacScan combines phage display, immunoprecipitation, and next-generation sequencing to comprehensively identify all the HIPs in a single assay, thereby paving the way for the development of universally protective vaccines. Our validation of this technique with Streptococcus suis, a major pathogenic threat, led to the identification of 19 HIPs, eight of which conferred 20-100% protection against S. suis challenge in animal models. Remarkably, HIP 8455 induced complete immunity, making it an exemplary vaccine target. BacScan’s adaptability to any bacterial pathogen positions it as a revolutionary tool that can expedite the development of vaccines with broad efficacy, thus playing a critical role in curbing bacterial transmission and slowing the march of antimicrobial resistance.

Parkinson’s disease (PD), ranking as the second most prevalent neurodegenerative disorder globally, presents a pressing need for innovative animal models to deepen our understanding of its pathophysiology and explore potential therapeutic interventions. The development of such animal models plays a pivotal role in unraveling the complexities of PD and investigating promising treatment avenues. In this study, we employed transcriptome sequencing on BmN cells treated with 1 μg/ml rotenone, aiming to elucidate the underlying toxicological mechanisms. The investigation brought to light a significant reduction in mitochondrial membrane potential induced by rotenone, subsequently triggering mitophagy. Notably, the PTEN induced putative kinase 1 (PINK1)/Parkin pathway emerged as a key player in the cascade leading to rotenone-induced mitophagy. Furthermore, our exploration extended to silkworms exposed to 50 μg/ml rotenone, revealing distinctive motor dysfunction as well as inhibition of Tyrosine hydroxylase (TH) gene expression. These observed effects not only contribute valuable insights into the impact and intricate mechanisms of rotenone exposure on mitophagy but also provide robust scientific evidence supporting the utilization of rotenone in establishing a PD model in the silkworm. This comprehensive investigation not only enriches our understanding of the toxicological pathways triggered by rotenone but also highlights the potential of silkworms as a valuable model organism for PD research.

BackgroundSingle-cell RNA sequencing (scRNA-Seq) provides new perspectives and ideas to investigate the interactions between different cell types and organisms. By integrating scRNA-seq with new computational frameworks or specific technologies, better Alzheimer’s disease (AD) treatments may be developed.MethodsThe single-cell sequencing dataset GSE158234 was obtained from the GEO database. Preprocessing, quality control, dimensionality-reducing clustering, and annotation to identify cell types were performed on it. RNA-seq profiling dataset GSE238013 was used to determine the components of specific cell subpopulations in diverse samples. A set of genes included in the OMIM, Genecards, CTD, and DisGeNET databases were selected as highly plausible AD-related genes. Then, ROC curves were created to predict the diagnostic value using the significantly expressed genes in the KO group as hub genes. The genes mentioned above were mapped to the Coremine Medical database to forecast prospective therapeutic Chinese medicines, and a “Chinese medicine-ingredient-target” network was constructed to screen for potential therapeutic targets. The last step was to undertake Mendelian randomization research to determine the causal link between the critical gene IL1B and AD in the genome-wide association study.ResultsUsing the scRNA-seq dataset, five unique cell clusters were discovered. These clusters were further subdivided into four distinct cell types using marker genes. The KO group showed a more substantial differential subgroup of macrophages than the WT group. By using the available datasets and PPI network analysis, 54 common genes were discovered. Four clusters were identified using the MCODE approach, and correlation analysis showed that seven genes in those four clusters had a significantly negative correlation with macrophages. Six genes in four sets had a significantly positive correlation. Five genes had different levels of expression in the WT and KO groups. The String database was used to identify the regulatory relationships between the four genes (IL10, CX3CR1, IL1B, and IL6) that were finally selected as AD hub genes. Screening identified potential traditional Chinese medicine to intervene in the transformation process of AD, including Radix Salviae, ginseng, Ganoderma, licorice, Coptidis Rhizoma, and Scutellariae Radix, in addition to promising therapeutic targets, such as PTGS1, PTGS2, and RXRA. Finally, it was shown that IL1B directly correlated with immune cell infiltration in AD. In inverse variance weighting, we found that IL1B was associated with a higher risk of AD, with an OR of 1.003 (95% CI = 1.001–1.006, p = 0.038).ConclusionOur research combined network pharmacology and the scRNA-seq computational framework to uncover pertinent hub genes and prospective traditional Chinese medicine potential therapeutic targets for AD. These discoveries may aid in understanding the molecular processes behind AD genes and the development of novel medications to treat the condition.

BackgroundEmerging infectious diseases pose a significant threat to both human and animal populations. Rapid de novo identification of protective antigens from a clinical isolate and development of an antigen-matched vaccine is a golden strategy to prevent the spread of emerging novel pathogens.MethodsHere, we focused on Actinobacillus pleuropneumoniae, which poses a serious threat to the pig industry, and developed a general workflow by integrating proteosurfaceomics, secretomics, and BacScan technologies for the rapid de novo identification of bacterial protective proteins from a clinical isolate.ResultsAs a proof of concept, we identified 3 novel protective proteins of A. pleuropneumoniae. Using the protective protein HBS1_14 and toxin proteins, we have developed a promising multivalent subunit vaccine against A. pleuropneumoniae.DiscussionWe believe that our strategy can be applied to any bacterial pathogen and has the potential to significantly accelerate the development of antigen-matched vaccines to prevent the spread of an emerging novel bacterial pathogen.

Cross-modal hashing methods have received wide attention in cross-modal retrieval owing to their advantages in computational efficiency and storage cost. However, most existing deep cross-modal hashing methods cannot employ both intra-modal and inter-modal similarities to guide the learning of hash codes and ignore the quantization loss of hash codes, simultaneously. To solve the above problems, we propose a fine-grained similarity semantic preserving deep hashing (FSSPDH) for cross-modal retrieval. Firstly, this proposed method learns different hash codes for different modalities to preserve the intrinsic property of each modality. Secondly, the fine-grained similarity matrix is constructed by using labels and data features, which not only maintains the similarity between and within modalities. In addition, quantization loss is used to learn hash codes and thus effectively reduce information loss caused during the quantization procedure. A large number of experiments on three public datasets demonstrate the advantage of the proposed FSSPDH method.