Zhanqi Dong

The cell cycle is a fundamental biological process indispensable for life, and its orderly progression is governed by a complex signaling network. Although the p38 MAPK pathway plays important roles in regulating cell proliferation across metazoans, its mechanistic role in insect cell cycle progression remains poorly characterized, particularly in species with endoreplication systems. Here, we investigated the function and mechanism of Bombyx mori p38 MAPK (Bmp38 MAPK) in cell cycle regulation using the silkworm silk gland as a specialized endoreplication model. We found that the p38 MAPK is evolutionarily conserved from insects to mammals and exhibits both cytoplasmic and nuclear localization, with its expression peaking during the G1 phase. Overexpression of Bmp38 MAPK induced cell cycle arrest at both G1/S and G2/M phases and suppressed cell proliferation, whereas Bmp38 MAPK knockdown alleviated G1/S arrest and enhanced proliferation. Mechanistically, Bmp38 MAPK increased BmCyclin B expression while reducing the expression of BmCyclin E, BmCDK2 and BmCDK1. Protein interaction assays further confirmed interactions between Bmp38 MAPK and BmCDK2, BmCyclin E and BmCyclin B. Notably, Bmp38 MAPK significantly inhibited DNA synthesis in silk gland cells, suggesting that Bmp38 MAPK contributes to the regulation of endoreplication. These findings reveal a possible role for p38 MAPK in insect cell cycle control and provide potential mechanistic insights into the regulation of endoreplication in the silkworm silk gland.

• 30 novel lncRNAs and 12 novel milRNAs were identified in N. bombycis. • A ceRNA network of N. bombycis lncRNAs, milRNA, and host miRNAs was constructed. • NbLNC2914 as a bmo-miR-2808a-3p sponge to regulate parasite proliferation. • The bmo-miR-2808a-3p suppressed the expression of NBO_58g0005 gene.

Microsporidia are unicellular eukaryotic obligate intracellular parasites that primarily infect vertebrates, invertebrates, and some protists. However, our understanding of microsporidian–host interaction mechanisms remains insufficient, especially the mechanisms underlying the noncoding RNA response to microsporidian infection. To systematically explore the characteristics of the host noncoding RNA response to microsporidian infection, we used whole‐transcriptome sequencing technology to identify noncoding RNAs in the Bombyx mori midgut at different time points after Nosema bombycis ( N. bombycis ) infection. We identified 51 novel microRNAs (miRNAs) and 269 novel circular RNAs (circRNAs) in the Bombyx mori midgut and constructed a differentially expressed (DE)‐circRNA–miRNA regulatory interaction network. Furthermore, our qRT‐PCR screening revealed that bmo_circ_0000157 (circ_0000157) facilitates N. bombycis proliferation. Ultimately, dual‐luciferase reporter and cell‐level rescue assays confirmed that circ_0000157 functions as a molecular sponge for bmo‐miR‐281‐5p (miR‐281‐5p), thereby regulating N. bombycis proliferation. Overall, our results indicate that the novel regulatory target circ_0000157 facilitates N. bombycis proliferation by modulating miR‐281‐5p expression, thereby altering its effects on downstream target genes. This study expands our understanding of circRNA biological functions and provides an important foundation for elucidating N. bombycis infection mechanisms.

Lissencephaly‐1 (Lis1) is a highly conserved cytoplasmic dynein regulator found in eukaryotes. It is involved in regulating processes such as cell proliferation, spindle orientation, nuclear migration, and microtubule‐dependent transport. Baculovirus frequently hijacks these cellular processes to facilitate infection and replication, whether Lis1 has a role during Baculovirus infection remains unexplored. This study found that Bombyx mori nucleopolyhedrovirus (BmNPV) infection downregulates Bombyx mori Lis1 (BmLis1) expression, suggesting its involvement in regulating viral replication. To investigate the function of BmLis1 during BmNPV infection, we performed flow cytometry, Western blotting, and qRT‐PCR analyses following BmLis1 overexpression and knockout. All results demonstrated that BmLis1 significantly suppresses BmNPV replication, as evidenced by changes in the expression levels of EGFP‐positive cells, VP39 protein, and key viral genes. Meanwhile, we demonstrated that BmLis1 significantly improves survival and inhibits viral proliferation in the BmLis1 ‐OE transgenic line. Moreover, we proved that BmLis1 inhibits viral replication by upregulating BmCyclin B expression, thereby reducing the proportion of cells in the G2/M phase of the cell cycle. More importantly, we found that BmNude1, an interacting protein of BmLis1, acts synergistically with BmLis1 to influence BmNPV proliferation by modulating BmCyclin B expression and G2/M phase progression. Collectively, these findings provide the first evidence that BmLis1 is a crucial host restriction factor against BmNPV infection that involves regulating cell cycle progression. These findings provide novel insights into the molecular mechanisms by which host factors combat baculovirus infection through modulation of the cell cycle.

Climate change-induced heat stress represents an increasing threat to biodiversity, engendering the need to understand evolutionary adaptations to thermal extremes. Using Bombyx mori as an economically important insect and research model, we employed genome-wide CRISPR/Cas9 screening integrated with high-throughput sequencing to systematically identify adaptations for heat resistance. The analysis identified the Bombyx mori membrane-bound alkaline phosphatase-like gene (BmM-ALP) as a vital thermoregulator. BmM-ALP triggered a pleiotropic protective cascade by significantly decreasing reactive oxygen species (ROS), suppressing apoptosis, and reprogramming mitochondrial metabolism via the phosphorylation of Vitamin B1 (VB1), suggesting a potential role in sustaining oxidative phosphorylation and enhancing energy metabolism under stress. Transgenic validation experiments confirmed the consistency of this strategy, and the BmM-ALP-OE strain displayed significantly enhanced thermal tolerance and prolonged survival under high-temperature stress. Beyond establishing BmM-ALP as a key gene of heat resistance in silkworms, this study uncovered a regulatory axis linking BmM-ALP to Vitamin B1 metabolism, illustrating a novel connection between energy homeostasis and thermal adaptation. The findings provide new insights that can be applied to breeding resistant strains in agriculture and biodiversity conservation in the context of global warming.

Baculoviruses, large double‐stranded DNA viruses, are widely used in biological control and biotechnology; however, their success depends on complex interactions with host factors. Members of the AAA ATPase family are emerging as key regulators in these processes. Previous studies identified Bombyx mori ATAD3A (BmATAD3A) as a host factor hijacked by the viral protein LEF‐11 to facilitate Bombyx mori nucleopolyhedrovirus (BmNPV) replication. However, the underlying mechanisms remain poorly understood. We generated transgenic silkworms overexpressing BmATAD3A and demonstrated that its overexpression enhances viral proliferation in vivo . Co‐immunoprecipitation (Co‐IP) combined with mass spectrometry analysis identified BmIGF2BP1 as an interacting protein of BmATAD3A. Further analysis showed that BmATAD3A negatively regulated the expression of BmIGF2BP1 . Additionally, our results showed that BmIGF2BP1 suppresses BmNPV replication, while BmATAD3A ‐mediated downregulation of BmIGF2BP1 further promotes viral proliferation. This study solidifies the critical role of ATAD3A in BmNPV replication, identifies its interacting proteins, and elucidates the functional interplay between BmIGF2BP1 and BmATAD3A in viral propagation. These findings advance our understanding of the mechanisms by which AAA ATPase family members regulate viral replication, thereby enriching the baculovirus–host interaction network.

Sericin, a natural macromolecular protein and the main component of silkworm cocoons, exhibits biocompatibility, excellent mechanical properties, and biodegradability. Previous research has confirmed that the sericin protein possesses anticancer properties. Gastric cancer (GC) poses a serious hazard to human health, with a low rate of early diagnosis and a poor prognosis. Investigating the safety and effectiveness of drugs for their used in treatment is imperative. In this study, we confirmed that Antherea pernyi sericin (APS) inhibited the proliferation, migration, and clonal formation of GC cells and caused apoptosis in the cells by regulating the expression of Bcl2 and Bax. Moreover, our data show that APS did not exhibit significant toxicity in normal gastric mucosal cells and mice. Furthermore, the results show that APS suppressed the proliferation of cisplatin-resistant GC cells and promoted cellular apoptosis; however, it had no synergistic effects with cisplatin. All the results indicated that APS exhibits antitumor activity against GC and is a prospective medicinal agent for the clinical treatment of GC, with minimal toxicity and adverse side effects. This research can provide a theoretical basis for sericin in the field of tumor treatment, especially for the application of natural macromolecular polypeptide drugs.