Harbin Normal University

Ultraviolet radiation (UVR) exposure increased in the past due to stratospheric ozone depletion, raising concerns about its long-lasting effects on freshwater ecosystems. While the ozone layer is gradually recovering, the effects of UVR on nutritional quality of periphyton as energy base for organisms in higher trophic levels in streams have not been understood. We conducted a manipulative experiment in mesocosm with four treatments (ambient, UVA, UVB, and combined UVA and UVB) to study the effects of UVR on nutritional quality of periphyton including oganic nutrient (long-chain polyunsaturated fatty acids, LC-PUFAs) and inorganic nutrient (P:C ratio) which both are nutritional quality biomarkers. UVR treatments significantly reduced periphyton nutritional quality represented by decreased LC-PUFAs i.e. eicosapentaenoic acid (EPA) under UVA, UVB, and UVAB treatments, while UVB and UVAB treatments resulted in the deficiency in phosphorus (P) in basal resources by a significant decrease in the P:C ratio. Specifically, LC-PUFAs decreased by approximately 40-50 % (from 5.20 % in the ambient to 2.61-3.20 %), and the P:C ratio decreased 2-3-fold (from 0.048 to 0.018-0.024) under UVR treatments. We found these the decrease of LC-PUFAs was linked to "shifts" of species in community, including a succession from Bacillariophyta to Chlorophytes and Cyanobacteria. It was revealed that UVR down regulated key enzymes in fatty acid biosynthesis and elongation, such as acetyl-CoA carboxylase (ACCase), 3-ketoacyl-CoA synthase (KCS), and omega-3 fatty acid desaturase (FAD3) associated with unsaturated fatty acid synthesis using transcriptomic analysis. These findings demonstrated that UVR exposure reduces the nutritional quality of periphyton as basal resources in stream food webs through community succession and down regulated genes encoding key enzymes.

Breast cancer remains the leading cause of cancer-related deaths because conventional therapies are constrained by systemic toxicity, insufficient specificity, and low patient adherence to patients. In this study, we developed a dissolvable microneedle (MN) platform integrating Bi/Bi₂SiO₅@SiO_2-x nanocomposites with gaseous prodrugs L-arginine (L-Arg) and ammonia borane (AB) for imaging-guided synergistic therapy. Bi-based nanocomposites exhibit strong near-infrared (NIR) absorption, efficient singlet oxygen (¹O₂) generation, and high X-ray attenuation, enabling effective tumor ablation and real-time computed tomography (CT) imaging. An appropriately designed SiO_2-x shell not only protects Bi from oxidation and prevents performance degradation but also efficiently captures the energy transferred from Bi, further facilitating ¹O₂ generation. The L-Arg and AB incorporated into the dissolvable MNs achieved a pH-responsive release of NO and H₂ following transdermal absorption, thereby enhancing photothermal, photodynamic, sonodynamic, and dual-gas synergistic therapies under NIR and ultrasound stimulation. In vitro and in vivo experiments confirmed its potent antitumor efficacy, outstanding biocompatibility, and minimal invasiveness. This study introduces a multifunctional therapeutic platform that addresses the key limitations of breast cancer therapy, offering a precise and non-invasive treatment strategy.

Immune checkpoint blockade (ICB) therapy has great potential in cancer therapy, but the patient response rate is low, mainly limited by hypoxia and insufficient infiltration of immunocompetent T cells in the immunosuppressive tumor microenvironment (TME), and Hypoxia-inducible factor-1α (HIF-1α) mediated high Programmed Cell Death-Ligand 1 (PD-L1) expression. In this study, hyaluronic acid (HA) modified hollow manganese dioxide (HMnO₂) nanocarriers (MCCMPH) were constructed via an innovative "in-situ synthesis-template etching" strategy to solve the above problems: this strategy physically locks copper-doped carbon dots (CuCDs) in the HMnO₂ cavity, addressing the issue of carbon dot detachment in traditional MnO₂@CDs materials. The nanocarrier is loaded with PDT photosensitizer methyl pyropheophorbide a (MPPa) and CuCDs with chemodynamic therapy (CDT)/photothermal therapy (PTT) functions. MCCMPH targets CD44 receptors on the surface of tumor cells through HA for precise delivery; HMnO₂ decomposes to produce oxygen in the tumor microenvironment, improves hypoxia, downregulates HIF-1α and PD-L1, and provides oxygen substrates for photodynamic therapy (PDT). The CDT and PTT of CuCDs synergistically interact with the PDT of MPPa, depleting glutathione (GSH) to cascade amplification of reactive oxygen species (ROS), significantly enhancing immunogenic death (ICD). In vitro and in vivo experiments have shown that MCCMPH can promote dendritic cell maturation, tumor-associated macrophage polarization from M2 to M1, and increase CD4⁺/CD8⁺T cell infiltration. In the dual-tumor model, it was combined with ICB to significantly inhibit the growth of primary and distant tumors, which proved to be effective in reversing the immunosuppressive TME and providing a new strategy for improving ICB response rate.