Qiuxiang Pang

As an alternative to perfluorooctane sulfonate (PFOS), 6:2 fluorotelomer sulfonic acid (6:2 FTSA) has been increasingly produced and detected in aquatic environments, yet its toxicological effects in fish remain incompletely characterized. In this study, adult female zebrafish were exposed for 30 days to solvent control (CK), 50 μg/L PFOS (P50), 50 μg/L 6:2 FTSA (F50), and 500 μg/L 6:2 FTSA (F500), respectively. Histopathological analysis revealed that both compounds induced hepatic injury, with the most severe damage observed in the F500 group. Hepatic transcriptomic analysis identified 645, 191, and 85 differentially expressed genes (DEGs) in the P50, F50, and F500 groups versus CK, respectively. Functional enrichment analysis further demonstrated distinct toxic profiles: PFOS at 50 μg/L primarily disrupted pathways related to the cell cycle, DNA replication, and reproduction. In contrast, 50 μg/L 6:2 FTSA predominantly activated PPAR-mediated lipid metabolism pathways, consistent with a “metabolic toxicity” phenotype. Notably, at 500 μg/L, 6:2 FTSA induced the most severe injury accompanied by a distinct transcriptomic signature—characterized by fewer DEGs but a pronounced enrichment of endoplasmic reticulum stress pathways—suggestive of a shift from metabolic perturbation to overwhelming cellular stress. Biochemical analysis confirmed a significant increase in malondialdehyde (MDA) only in the F50 group, supporting oxidative stress-mediated metabolic toxicity. Collectively, these findings demonstrate that 6:2 FTSA is not a safe alternative to PFOS but exhibits a dose-dependent and multifaceted toxicological profile, with high-dose effects indicative of acute cellular stress. This study underscores the need for case-specific, dose-range inclusive risk assessment of emerging PFAS alternatives.

Potassium sorbate (PS) is a widely used antimicrobial additive employed as a preservative in food, cosmetics, and animal feed. Early childhood represents a critical developmental window characterized by rapid growth, immune system maturation, gut microbiota establishment, and physiological homeostasis development, which may be particularly vulnerable to chemical exposures (during which chemical exposures may exert heightened impacts). Nevertheless, the effects of PS on childhood development and gut microbiota remain poorly understood, and its potential trans-generational effects have yet to be elucidated. In this study, we employed Drosophila melanogaster , an established model for studying evolutionarily conserved aspects of development, metabolism, and host–microbiota interactions, to systematically evaluate PS toxicity across multiple parameters: developmental dynamics, gut microbiota composition, gene regulation in adulthood, and trans-generational effects. Our findings demonstrate a dose-dependent biphasic response: while low-dose PS exposure (25 mg/L) accelerated larval pupation and adult emergence, suggesting a potential growth-promoting effect, high-dose exposure (≥ 500 mg/L) significantly delayed development and reduced adult lifespan (observed in females at 1,000 and males at 500–1,000 mg/L). Notably, trans-generational analysis revealed persistent developmental delays in the F1 generation, with offspring of 1,000 mg/L-exposed parents showing prolonged larval pupation time despite normal adult emergence timelines, indicative of partial developmental recovery. Mechanistically, high-dose PS disrupted endocrine signaling and altered expression of key developmental pathway regulators ( EcR , InR , TOR , and E74B ). These transcriptional changes were largely reversible in offspring, further supporting a similar gradually wash out recovery. While gut microbiota remained stable in exposed parents, offspring of 1,000 mg/L-exposed flies had significant microbiome alterations, highlighting clear trans-generational dysbiosis. This study provides new evidence that PS exposure during a sensitive developmental period in D. melanogaster can perturb development and gut microbial homeostasis across generations, offering insights relevant to understanding how early-life chemical exposures might influence conserved biological processes in higher organisms.

α2-Macroglobulin (A2M), a large tetrameric glycoprotein with a molecular weight of approximately 720 kDa, is a key member of the α-macroglobulin superfamily. Its origin dates back 600–700 million years, positioning A2M as an evolutionary link within the α-macroglobulin family and complement components C3, C4, and C5. Structural predictions of A2M across different species reveal a remarkably high degree of conservation between invertebrates and vertebrates. A2M is abundantly present in the body fluids of both vertebrates and invertebrates, and its diverse biological functions are governed by five key functional domains within its molecular structure. The most well-established role of A2M is the entrapment and inhibition of proteases. Beyond that, it interacts with cytokines, growth factors, and membrane receptors, thereby playing a broad role in immune and inflammatory responses, hemostasis and coagulation, as well as in disease mechanisms and therapeutic processes. This review summarizes the origin and evolution of A2M, its molecular structure and functional domains, principal mechanisms of action, and research progress regarding its functions in both invertebrates and vertebrates. Our goal is to provide new insights and directions for further exploring the functional potential of A2M and its future applications in the treatment of clinical diseases.

The isolation of intact, high-molecular-weight genomic DNA (HMW gDNA) is essential for achieving complete genome assemblies. However, extracting HMW gDNA from a single individual of Dugesia japonica remains a technical challenge using the standard protocol, probably due to the presence of abundant polysaccharides and nucleases. In this study, we have developed a more robust protocol for preparing HMM gDNA, with high yields and quality, from a single D. japonica. The key step in our protocol involves the use of a Mg2+-dependent lysis buffer, rather than using metal cation chelation to block the activities of DNase I as in the standard protocol. Using this approach were able to achieve a yield of about 10–15 µg of HWM gDNA per worm. Our method showed species- and region-specific effectiveness, with optimal results observed at 20 mM Mg2+ for our local D. japonica specimens. The extracted HMW gDNA is fully compatible with advanced long-read sequencing platforms such as PacBio HiFi and Oxford Nanopore. However, when applied to Schmidtea mediterranea and D. japonica specimens from Beijing, the method was ineffective and led to progressive gDNA degradation. This protocol offers a simple and high-yield solution for isolating HMW gDNA from D. japonica. It also provides an alternative for organisms whose gDNA consistently exhibits unexplained degradation using established protocols.

The carboxy-terminal postsynaptic density protein 95/discs large protein/zonula occludens 1 (PDZ) ligand of neuronal nitric oxide synthase (nNOS), known as CAPON, can interact with nNOS to influence neuropathological processes. However, the precise mechanism by which CAPON regulates neuronal regeneration remains poorly understood. In this study, we utilized the planarian Dugesia japonica, a model organism renowned for its remarkable regenerative abilities, to investigate this mechanism. First, we cloned the DjCapon gene and performed RNA interference (RNAi) to knock down DjCapon expression in planarians. Our results revealed that DjCapon knockdown impaired neural regeneration, particularly affecting the regeneration of GABAergic neurons. This impairment led to a reduced sensitivity to light in planarians. Furthermore, DjCapon knockdown decreased the activity of nitric oxide synthase (NOS) and reduced the levels of nitric oxide (NO) in planarians. During neural regeneration, the expression of genes associated with the Wnt/Ca²⁺ signaling pathway, including DjWnt5a, calcineurin (DjCaln), and calcium/calmodulin-dependent protein kinase II (DjCamKII), was upregulated following DjCapon knockdown. In summary, our findings demonstrate that DjCapon plays a critical role in regulating neural regeneration. DjCapon may modulate the Wnt/Ca²⁺ signaling pathway by influencing NOS activity and NO levels. Additionally, the Wnt/Ca²⁺ pathway appears to regulate the regeneration of GABAergic neurons and light sensitivity in planarians. These results provide new insights into the mechanism by which CAPON influences neural regeneration and its potential implications for related diseases.

Stem cells and regenerative medicine have recently become important research topics. However, the complex stem cell regulatory networks involved in various microRNA (miRNA)-mediated mechanisms have not yet been fully elucidated. Planarians are ideal animal models for studying stem cells owing to their rich stem cell populations (neoblasts) and extremely strong regeneration capacity. The roles of planarian miRNAs in stem cells and regeneration have long attracted attention. However, previous studies have generally provided simple datasets lacking integrative analysis. Here, we have summarized the miRNA family reported in planarians and highlighted conservation in both sequence and function. Furthermore, we summarized miRNA data related to planarian stem cells and regeneration and screened potential involved candidates. Nevertheless, the roles of these miRNAs in planarian regeneration and stem cells remain unclear. The identification of potential stem cell-related miRNAs offers more precise suggestions and references for future investigations of miRNAs in planarians. Furthermore, it provides potential research avenues for understanding the mechanisms of stem cell regulatory networks. Finally, we compiled a summary of the experimental methods employed for studying planarian miRNAs, with the aim of highlighting special considerations in certain procedures and providing more convenient technical support for future research endeavors.

The highly conserved Notch signaling pathway affects embryonic development, neurogenesis, homeostasis, tissue repair, immunity, and numerous other essential processes. Although previous studies have demonstrated the location and function of the core components of Notch signaling in various animal phyla, a more comprehensive summary of the Notch core components in lower organisms is still required. In this review, we objectively summarize the molecular features of the Notch signaling pathway constituents, their current expression profiles, and their functions in invertebrates, with emphasis on their effects on neurogenesis and regeneration. We also analyze the evolution and other facets of Notch signaling and hope that the contents of this review will be useful to interested researchers.