The mud snail Cipangopaludina cathayensis is a widely distributed species in China. Particularly in Guangxi province, mud snail farming contributes significantly to the economic development. However, global warming in recent decades poses a serious threat to global aquaculture production. The rising water temperature is harmful to aquatic animals. The present study explored the effects of high temperature on the intestinal microbiota of C. cathayensis. Snail intestinal samples were collected from the control and high-temperature groups on days 3 and 7 to determine the gut microbiota composition and diversity. Gut bacterial community composition was investigated using high-throughput sequencing of the V3–V4 region of bacterial 16S rRNA genes. Our results suggested that thermal stress altered the gut microbiome structure of C. cathayensis. At the phylum level, Proteobacteria, Bacteroidetes, and Firmicutes were dominant in C. cathayensis gut microbiota. The T2 treatment (32 ± 1 °C, day 7) significantly decreased the relative abundance of Firmicutes, Actinobacteria, and Deinococcus-Thermus. In T2, the abundance of several genera of putatively beneficial bacteria (Pseudomonas, Aeromonas, Rhodobacter, and Bacteroides) decreased, whereas the abundance of Halomonas—a pathogenic bacterial genus—increased. The functional prediction results indicated that T2 treatment inhibited some carbohydrate metabolism pathways and induced certain disease-related pathways (e.g., those related to systemic lupus erythematosus, Vibrio cholerae infection, hypertrophic cardiomyopathy, and shigellosis). Thus, high temperature profoundly affected the community structure and function of C. cathayensis gut microbiota. The results provide insights into the mechanisms associated with response of C. cathayensis intestinal microbiota to global warming.

Hepatocellular carcinoma (HCC) is a highly heterogeneous and immunosuppressive malignancy that frequently exhibits poor responses to immunotherapy, primarily due to immune evasion mediated by myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. Despite increasing interest in MDSC-targeted strategies, effective approaches to selectively modulate MDSC function and enhance immunotherapeutic efficacy remain limited. Recent advances in nanotechnology have led to the development of nanodrug delivery systems, particularly for small interfering RNA (siRNA), offering advantages such as protection from degradation and improved delivery specificity. However, traditional liposomal carriers often suffer from low selectivity and widespread biodistribution, increasing the risk of off-target effects. In this study, we designed a pH-responsive lipid nanoparticle (Lip@si-YTHDF2) for the targeted delivery of siRNA against YTHDF2. This approach aimed to suppress MDSC function, inhibit CSC-mediated immune escape, and enhance immunotherapy in HCC. Bioinformatic analyses of GEO and TCGA-LIHC datasets revealed elevated YTHDF2 expression in HCC and its association with poor prognosis. Functional studies in a conditional YTHDF2-knockout mouse model demonstrated that YTHDF2 regulates MDSC activity and promotes tumor progression by stabilizing MYC mRNA through N6-methyladenosine (m6A) modification. Our findings demonstrated that Lip@si-YTHDF2 effectively downregulated MYC expression, diminished the immunosuppressive phenotype of MDSCs, restored T cell-mediated anti-tumor immunity, and significantly inhibited tumor growth in combination with PD-1 checkpoint blockade. This study not only elucidates a novel YTHDF2/m6A/MYC axis in immune evasion but also provides a clinically relevant siRNA delivery platform with promising therapeutic implications for improving HCC immunotherapy.

Ocean acidification and warming are two of the most important threats to the existence of marine organisms and are predicted to co-occur in oceans. The present work evaluated the effects of acidification (AC: 24 ± 0.1 °C and 900 μatm CO₂), warming (WC: 30 ± 0.1 °C and 450 μatm CO₂), and their combination (CC: 30 ± 0.1 °C and 900 μatm CO₂) on the sea anemone, Heteractis crispa, from the aspects of photosynthetic apparatus (maximum quantum yield of photosystem II (PS II), chlorophyll level, and Symbiodiniaceae density) and sterol metabolism (cholesterol content and total sterol content). In a 15-day experiment, acidification alone had no apparent effect on the photosynthetic apparatus, but did affect sterol levels. Upregulation of their chlorophyll level is an important strategy for symbionts to adapt to high partial pressure of CO₂ (pCO₂)_. However, after warming stress, the benefits of high pCO₂ had little effect on stress tolerance in H. crispa. Indeed, thermal stress was the dominant driver of the deteriorating health of H. crispa. Cholesterol and total sterol contents were significantly affected by all three stress conditions, although there was no significant change in the AC group on day 3. Thus, cholesterol or sterol levels could be used as important indicators to evaluate the impact of climate change on cnidarians. Our findings suggest that H. crispa might be relatively insensitive to the impact of ocean acidification, whereas increased temperature in the future ocean might impair viability of H. crispa.