Search Results (57)

As a pivotal model organism in Lepidoptera research, the silkworm (Bombyx mori) holds significant importance in life science due to its economic value and biotechnological applications. Advancements in proteomics and bioinformatics have enabled substantial progress in characterizing the B. mori proteome. Systematic screening and identification of protein–protein interactions (PPIs) have progressively elucidated the molecular mechanisms governing key biological processes, including viral infection, immune regulation, and growth development. This review comprehensively summarizes traditional PPI detection techniques, such as yeast two-hybrid (Y2H) and immunoprecipitation (IP), alongside emerging methodologies such as mass spectrometry-based interactomics and artificial intelligence (AI)-driven PPI prediction. We critically analyze the strengths, limitations, and technological integration strategies for each approach, highlighting current field challenges. Furthermore, we elaborate on the molecular regulatory networks of Bombyx mori nucleopolyhedrovirus (BmNPV) from multiple perspectives: apoptosis and cell cycle regulation; viral protein invasion and trafficking; non-coding RNA-mediated modulation; metabolic reprogramming; and host immune evasion. These insights reveal the dynamic interplay between viral replication and host defense mechanisms. Collectively, this synthesis aims to provide a robust theoretical foundation and technical guidance for silkworm genetic improvement, infectious disease management, and the advancement of related biotechnological applications. Full article

The real estate sector is increasingly recognizing facility management (FM) as a key driver of asset value. Among emerging technologies, Building Information Modeling (BIM) and Building Management Systems (BMSs) stand out for their potential to enhance FM efficiency by integrating design data with building operations across the entire lifecycle, from construction to maintenance, performance monitoring, and renovation. While their technical applications have been widely studied, the financial impact of these tools on FM remains underexplored. This paper addresses that gap by estimating the economic value generated by implementing BIM and BMS in real estate facility management. Based on thirteen semi-structured interviews with professionals from the Italian real estate sector, we identified and quantified cost-saving factors and challenges related to digital adoption. These cost efficiencies, when recurring and quantifiable, can improve net operating income (NOI), thereby supporting higher asset valuations under income-based real estate appraisal methods. The results show that integrating BIM and BMS in facility management may generate average annual cost savings of 5.81% relative to asset value, with coordination improvements alone accounting for up to 3.28% per year. Based on a 30-year simulation, these savings correspond to a positive Net Present Value (NPV), supporting the financial viability of digital FM adoption in real estate. This study offers empirical evidence to support investment decisions in digital FM technologies and contributes to bridging the gap between innovation and financial evaluation in the real estate sector. Full article

A nuclear export signal (NES) is a cluster of hydrophobic amino acids that can maintain the dynamic shuttling of target proteins between the nucleus and cytoplasm. Bioinformatics analysis showed that the hydrophobic region of ⁹²PLLLHKFLLA in Bm65 is very likely to be an NES and may be involved in the production of infectious virions. In this study, we generated several mutations in ⁹²PLLLHKFLLA of Bm65, which were further used to generate recombinant viruses to study their roles in viral propagation. Subcellular analysis revealed that the ⁹²PLLLHKFLLA sequence was an NES involved in the dynamic transport of Bm65. Mutations in the hydrophobic region could block the formation and accumulation of Bm65 aggregates, resulting in a uniform distribution of Bm65 in BmN cells. The ribosomal protein L13 (RPL13) of silkworms was previously reported to interact with Bm65. Here, intracellular co-localization analysis showed that the interaction between Bm65 and RPL13 was regulated by the ⁹²PLLLHKFLLA of Bm65. In summary, the interaction between Bm65 and RPL13 is essential for the production and accumulation of Bm65 aggregates and may play an important role in the regulation of viral propagation. Full article

Solar ultraviolet radiation (UV) may cause DNA damage. We first report in this study that the large subunit ribosome protein RPL12, from Bomby mori (BmRPL12), participated in UV-induced DNA damage repair. BmRPL12 enhanced the resistance of Escherichia coli (E. coli) to UV radiation and facilitated faster repair of UV-induced DNA damage in silkworm cells. BmRPL12 mainly existed in the cytoplasm in the dimer forms, and the N-terminal nuclear export signal was crucial for the localization of BmRPL12. After UV radiation, BmRPL12 was unable to localize at the UV-induced DNA damage sites to participate in damage repair directly and might indirectly regulate UV-induced DNA damage repair. Our previous research found that BmNPV Bm65 was an important UV damage-induced endonuclease. Here, it was further found that in BmNPV-infected silkworm cells, BmRPL12 in monomeric forms interacted with the virus Bm65 protein only after UV radiation, and BmRPL12 specifically localized at the UV-induced DNA damage sites only in the presence of Bm65. We speculate that after viral infection in cells subjected to UV-induced DNA damage, viral protein Bm65 interacts with BmRPL12 and localizes BmRPL12 to sites of UV-damaged DNA. Full article

Pathogenic infections of silkworms constitute the greatest threat to sericulture. An attractive approach to the improvement in silkworm health and performance comprises the use of probiotics, i.e., microorganisms that confer beneficial properties such as an increased growth rate and resistance against pathogens. While this method has already resulted in promising results, generally, there is a lack of a rational basis for guidance on the selection of probiotics. This review attempts to organize useful information that needs to be considered for the successful application of probiotics: the constitution of the microbiota in silkworms and its origins; the interaction of the major silkworm pathogens with the microbiota; and the microorganisms that have been used so far as silkworm probiotics. Our analysis points to two major issues that seem of vital importance: (1) the absence of a “core microbiota” in silkworms which necessitates continuous supply of beneficial microorganisms according to environmental conditions and (2) the apparent negative impact that some other microorganisms can have on resistance against baculovirus infections. Recent findings have reported the beneficial effects of lactic acid bacteria (Lactobacillus sp.) when applied as probiotics in improving silkworm health and performance. Full article

Baculoviruses, the largest studied insect viruses, are highly pathogenic to host insects. Bombyx mori nucleopolyhedrovirus (BmNPV) is the main cause of nuclear polyhedrosis of silkworm, a viral disease that causes significant economic losses to the sericulture industry. The anti-BmNPV mechanism of the silkworm has not yet been characterized. Carboxypeptidase is an enzyme that is involved in virtually all life activities of animals and plants. Studies have shown that the carboxypeptidase family is related to insect immunity. There are few reports on the role of carboxypeptidase in the defense of silkworms against pathogen invasion. In this study, we identified the homologous gene Bombyx mori metal carboxypeptidases12 (BmMCP12) related to mammalian carboxypeptidase A2 (CPA2) and found that BmMCP12 had a Zn-pept domain. The BmMCP12 gene was primarily located in the cytoplasm and was highly expressed in the midgut of silkworms, and the expression level in BmN-SWU1 cells was upregulated after infection with BmNPV. After overexpression of the BmMCP12 gene, quantitative real-time (qRT)-PCR and Western blots showed that BmMCP12 could inhibit BmNPV replication, whereas knockout of the gene had the opposite effect. In addition, we constructed transgenic silkworm strains with a knockout of BmMCP12, and the transgenic strains had reduced resistance to BmNPV. These findings deepen the functional study of silkworm carboxypeptidase and provide a new target for BmNPV disease prevention in silkworms. Full article

The resistance of silkworms to Bombyx mori nuclear polyhedrosis virus (BmNPV) is controlled by a major dominant gene and multiple modifying genes. Given the presence of modified genes, it is difficult to determine the main gene by positional cloning. In this study, the main anti-BmNPV gene of BmNPV-resistant silkworm variety N was introduced into the susceptible variety Su to breed the near-isogenic line SuN with BmNPV resistance. The infection process of BmNPV in the hemolymph of Su and SuN was analyzed using the cell analysis system TissueFAXS PLUS. According to the law of infection and proliferation, hemolymph was extracted every 6 h for two-dimensional electrophoresis (2-DE) analysis and quantitative real-time polymerase chain reaction (qRT-PCR). Seven DEPs were found in comparisons between Su and SuN by 2-DE analysis. Among them, acid phosphatase, storage protein, and phenoloxidase can prevent pathogen invasion, which may play a role against BmNPV. Polyamine oxidase plays an important role in energy metabolism, which may be indirectly involved in the process of resisting BmNPV. Most of the transcriptional expression profiles of the seven DEPs were consistent with the 2-DE results. This study can provide a reference for the identification of anti-BmNPV genes and the breeding of BmNPV-resistant silkworm varieties. Full article

Trehalose is a non-reducing disaccharide and participates in physiological activities such as organ formation, energy metabolism, and stress resistance in insects. The Bmtret1 gene family is mainly involved in in the sugar metabolism of silkworm. In the present study, phylogenetic analysis divided 21 Bmtret1 orthologs into three clades. These genes are equally distributed on the nine chromosomes. The cis-elements in the promoter regions of Bmtret1s indicated the possible function of Bmtret1s in response to hormones and environmental stimulus. The qPCR analysis showed the significantly different expression levels of Bmtret1s in different tissues and organs, indicating possible functional divergence. In addition, most Bmtret1s showed disturbed expression levels in response to silkworm nuclear polyhedrosis virus (BmNPV) stresses. Our results provide a clue for further functional dissection of the Tret1s in Bombyx mori and implicate them as potential regulators of antiviral responses. Full article

Bombyx mori nucleopolyhedrovirus (BmNPV) is a specific pathogen of Bombyx mori that can significantly impede agricultural development. Accumulating evidence indicates that the viral proliferation in the host requires an ample supply of energy. However, the correlative reports of baculovirus are deficient, especially on the acetylation modification of tricarboxylic acid cycle (TCA cycle) metabolic enzymes. Our recent quantitative analysis of protein acetylome revealed that mitochondrial aconitase (ACO2) could be modified by (de)acetylation at lysine 56 (K56) during the BmNPV infection; however, the underlying mechanism is yet unknown. In order to understand this regulatory mechanism, the modification site K56 was mutated to arginine (Lys56Arg; K56R) to mimic deacetylated lysine. The results showed that mimic deacetylated mitochondrial ACO2 restricted enzymatic activity. Although the ATP production was enhanced after viral infection, K56 deacetylation of ACO2 suppressed BmN cellular ATP levels and mitochondrial membrane potential by affecting citrate synthase and isocitrate dehydrogenase activities compared with wild-type ACO2. Furthermore, the deacetylation of exogenous ACO2 lowered BmNPV replication and generation of progeny viruses. In summary, our study on ACO2 revealed the potential mechanism underlying WT ACO2 promotes the proliferation of BmNPV and K56 deacetylation of ACO2 eliminates this promotional effect, which might provide novel insights for developing antiviral strategies. Full article

Nuclease is a type of protein that degrades nucleic acids, which plays an important role in biological processes, including RNA interference efficiency and antiviral immunity. However, no evidence of a link between nuclease and Bombyx mori nucleopolyhedrovirus (BmNPV) infection in silkworm B. mori has been found. In this study, a protein asteroid (BmAst) containing the PIN domain and XPG domain was identified in silkworm B. mori. BmAst gene was highest expressed in hemocytes and fat body of the 5th instar larvae, and high expression in the pupa stage. The transcriptional levels of the BmAst gene in 5th instar larvae were significantly induced by BmNPV or dsRNA. After knocking down BmAst gene expression by specific dsRNA, the proliferation of BmNPV in B. mori was increased significantly, whereas the survival rate of larvae was significantly lower when compared with the control. Our findings indicate that BmAst is involved in silkworm resistance to BmNPV infection. Full article

Purpose: To identify clinical risk factors, including gross tumor volume (GTV) and radiomics features, for developing brain metastases (BM) in patients with radically treated stage III non-small cell lung cancer (NSCLC). Methods: Clinical data and planning CT scans for thoracic radiotherapy were retrieved from patients with radically treated stage III NSCLC. Radiomics features were extracted from the GTV, primary lung tumor (GTVp), and involved lymph nodes (GTVn), separately. Competing risk analysis was used to develop models (clinical, radiomics, and combined model). LASSO regression was performed to select radiomics features and train models. Area under the receiver operating characteristic curves (AUC-ROC) and calibration were performed to assess the models’ performance. Results: Three-hundred-ten patients were eligible and 52 (16.8%) developed BM. Three clinical variables (age, NSCLC subtype, and GTVn) and five radiomics features from each radiomics model were significantly associated with BM. Radiomic features measuring tumor heterogeneity were the most relevant. The AUCs and calibration curves of the models showed that the GTVn radiomics model had the best performance (AUC: 0.74; 95% CI: 0.71–0.86; sensitivity: 84%; specificity: 61%; positive predictive value [PPV]: 29%; negative predictive value [NPV]: 95%; accuracy: 65%). Conclusion: Age, NSCLC subtype, and GTVn were significant risk factors for BM. GTVn radiomics features provided higher predictive value than GTVp and GTV for BM development. GTVp and GTVn should be separated in clinical and research practice. Full article

Bombyx mori nucleopolyhedrovirus (BmNPV) is a serious threat to sericulture. Nevertheless, no effective control strategy is currently available. The innate immunity of silkworm is critical in the antiviral process. Exploring its molecular mechanism provides theoretical support for the prevention and treatment of BmNPV. Insect hormone receptors play an essential role in regulating host immunity. We found a correlation between Bombyx mori ecdysone receptor B1 (BmEcR-B1) and BmNPV infection, whereas the underlying mechanism remains unclear. In this study, the expression patterns and sequence characteristics of BmEcR-B1 and its isoform, BmEcR-A, were initially analyzed. BmEcR-B1 was found to be more critical than BmEcR-A in silkworm development and responses to BmNPV. Moreover, RNAi and an overexpression in BmN cells showed BmEcR-B1 had antiviral effects in the presence of 20-hydroxyecdysone (20E); Otherwise, it had no antiviral activity. Furthermore, BmEcR-B1 was required for 20E-induced apoptosis, which significantly suppressed virus infection. Finally, feeding 20E had no significant negative impacts on larval growth and the cocoon shell, suggesting the regulation of this pathway has practical value in controlling BmNPV in sericulture. The findings of this study provide important theoretical support for understanding the mechanism of the silkworm innate immune system in response to BmNPV infection. Full article

Homologs of Autophagy-related (Atg) protein 4 are reported to cleave LC3 protein and facilitate autophagy occurrence differently in mammals, whereas their functions have not been investigated in insects. Three homologs, including BmAtg4a and its short form BmAtg4c as well as BmAtg4b, exist in Bombyx mori. Herein, the autophagic functions of BmAtg4a and BmAtg4b were investigated. qPCR detection found that BmAtg4a and BmAtg4b both peaked during larval-pupal metamorphosis when autophagy occurs robustly. Immunofluorescent staining showed that BmAtg4a was predominantly localized at the cytoplasm, while BmAtg4b had notable nuclear localization. Overexpression of BmAtg4a and BmAtg4b both slightly promoted basal autophagy but inhibited the autophagy induced by the infection of B. mori nucleopolyhedrovirus (BmNPV) and, thereby, its proliferation. In comparison, knockout of BmAtg4a or BmAtg4b significantly upregulated BmNPV-induced autophagy and its replication in BmN cells. Results of Co-immunoprecipitation associated with mass spectrum showed that the cytoskeleton protein B. mori actin A2 (BmACT2) and B. mori actin A1 (BmACT1) bound with BmAtg4a and BmAtg4b especially. Knockout of BmACT1 and BmACT2 inhibited BmAtg4b- and BmAtg4a-induced autophagy, respectively; moreover, knockout of BmACT1 reduced the ratio of cells with nuclear BmAtg4b. Of note, BmAtg4a and BmAtg4b had physical interaction, and they had an inhibitory effect on mutual autophagic function. In this work, we provide new insights into the autophagy machinery in insects as well as its function in the proliferation of BmNPV. Full article

The glucose regulated protein (GRP78) is an important chaperone for various environmental and physiological stimulations. Despite the importance of GRP78 in cell survival and tumor progression, the information regarding GRP78 in silkworm Bombyx mori L. is poorly explored. We previously identified that GRP78 expression was significantly upregulated in the silkworm Nd mutation proteome database. Herein, we characterized the GRP78 protein from silkworm B. mori (hereafter, BmGRP78). The identified BmGRP78 protein encoded a 658 amino acid residues protein with a predicted molecular weight of approximately 73 kDa and comprised of two structural domains, a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). BmGRP78 was ubiquitously expressed in all examined tissues and developmental stages by quantitative RT-PCR and Western blotting analysis. The purified recombinant BmGRP78 (rBmGRP78) exhibited ATPase activity and could inhibit the aggregating thermolabile model substrates. Heat-induction or Pb/Hg-exposure strongly stimulated the upregulation expression at the translation levels of BmGRP78 in BmN cells, whereas no significant change resulting from BmNPV infection was found. Additionally, heat, Pb, Hg, and BmNPV exposure resulted in the translocation of BmGRP78 into the nucleus. These results lay a foundation for the future identification of the molecular mechanisms related to GRP78 in silkworms. Full article