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Cancer nanomedicine combined with immunotherapy has emerged as a promising strategy for the treatment of cancer. However, precise regulation of the activation of antitumor immunity in targeting tissues for safe and effective cancer immunotherapy remains challenging. Herein, we report a tumor acidic microenvironment-responsive promodulator iron oxide nanoparticle (termed as FGR) with pH-activated action for photothermal-enhanced chemodynamic immunotherapy of cancer. FGR is formed via surface-modifying iron oxide nanoparticles with a dextran-conjugated Toll-like receptor agonist (R848) containing an acid-labile bond. In an acidic tumor microenvironment, the acid-responsive bonds are hydrolyzed to trigger the specific release of R848 to promote the maturation of dendritic cells. In addition, iron oxide nanoparticles within FGR exert photothermal and chemodynamic effects under near-infrared laser irradiation to directly kill tumor cells and induce immunogenic cell death. The synergistic effect of the released immunogenic factors and the acid-activated TLR7/8 pathway stimulates the formation of strong antitumor immunity, resulting in increased infiltration of cytotoxic CD8

Immunotherapy has been used for cancer treatment, while it faces the common dilemmas of low therapeutic efficacy and serious immunotoxicity. In this study, we report the construction of a tumor microenvironment and near-infrared (NIR) light dual-responsive prodrug hydrogel for cancer synergistic immunotherapy in a more effective and safe manner. Such prodrug hydrogels were in-situ formed via calcium-induced gelation of alginate solution containing protoporphyrin IX (PpIX)-modified iron oxide (Fesub3/subOsub4/sub) nanoparticles and programmed death ligand 1 antibody (aPD-L1) prodrug nanoparticles crosslinked by reactive oxygen species (ROS)-responsive linkers. PpIX served as a photosensitizer to produce singlet oxygen (sup1/supOsub2/sub) under NIR laser irradiation for photodynamic therapy (PDT), and Fesub3/subOsub4/subnanoparticles mediated chemodynamic therapy (CDT) to generate hydroxyl radical (·OH) via Fenton reaction in the tumor microenvironment. In view of the cumulative actions of PDT and CDT, amplified ROS was generated to not only induce immunogenic cell death (ICD), but also destroy ROS-responsive linkers to achieve on-demand release of aPD-L1 from prodrug nanoparticles. Boosted antitumor immunity was elicited in tumor-bearing mice due to the aPD-L1-mediated immune checkpoint blocking. As a result, the prodrug hydrogel-based synergistic immunotherapy could almost treat bilateral tumors and prevent lung and liver metastasis using 4T1 tumor mouse models. This study thus offers a dual-responsive prodrug hydrogel platform for precision cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Via calcium-induced gelation of alginate, we constructed a prodrug hydrogel with tumor microenvironment and near-infrared light dual-responsive action for synergistic cancer immunotherapy. Such hydrogels can achieve on-demand release of aPD-L1 upon photoactivation in the tumor microenvironment. Through mediating photodynamic and chemodynamic therapy, the prodrug hydrogels can induce enhanced immunogenic cell death and synergistically improve the efficacy of aPD-L1-mediated immune checkpoint blocking. The prodrug hydrogel-based synergistic therapy almost deracinates the primary and distant tumors, and prevents lung and liver metastasis in tumor mouse models.

The surface structure and topography of biomaterials play a crucial role in directing cell behaviors and fates. Meanwhile, asymmetric dressings that mimic the natural skin structure have been identified as an effective strategy for enhancing wound healing. Inspired by the skin structure and the superhydrophobic structure of the lotus leaf, an asymmetric composite dressing was obtained by constructing an asymmetric structure and wettability surface modification on both sides of the sponge based on electrospinning. Among them, the collagen and quaternized chitosan sponge was fabricated by freeze-drying, followed by an aligned poly(ε-caprolactone) (PCL)/gelatin nanofiber hydrophilic inner layer and hierarchical micronanostructure PCL/polystyrene microsphere highly hydrophobic outer layer constructed on each side of the sponge. The proposed asymmetric composite dressing combines topological morphology with the material's properties to effectively prevent bacterial colonization/infection and promote wound healing by directing cellular behavior.

Suitable treatment of toilet sewage is a worldwide challenge. The anaerobic baffled reactor (ABR)-microbial fuel cell (MFC)-microbial electrolysis cell (MEC) (AMM) coupling treatment system has been constructed achieving effective removal of carbon, nitrogen, and phosphorus from toilet sewage and resource recovery; however, ammonium (NH4 + -N) and total phosphorus (TP) accumulation in tail water is a found problem of the system. In this study, acid-modified and alkali-heat modified palygorskite-bentonite (Pal-Ben) were used to recover NH4 + -N and TP from the AMM toilet tail water simultaneously. The higher adsorption capacity of the modified clay is attributed to the changes of surface structure of the material. The modified clay Pal-Ben (mass ratio 1:3) activated with alkali performed the highest NH4 + -N and TP recovery rates of 83.6% and 85.5%, respectively. The adsorption of NH4 + -N was more in line with the pseudo-second-order kinetic model and confirmed to be a chemical adsorption process, while the adsorption of TP was more in line with the pseudo-first-order kinetics and a physical adsorption process; the adsorption capacity of NH4 + -N accelerated with decrease of TP removal when pH increased. This study developed a low cost and high capacity of alkaline thermally modified clay removing/recovering NH4 + -N and TP from toilet tail water simultaneously. PRACTITIONER POINTS: A cheap composite clay was developed to recover nitrogen and phosphorus from toilet tail water simultaneously. The low costs and high capacity of alkaline thermally modified clay make it stand out in NH4 + -N and TP removal of toilet tail water. The process mechanism of simultaneous nitrogen and phosphorus recovery was clarified with characterization and kinetic model fitting. The used clay loaded with nutrients could be applied as a slow-release compound fertilizer for soil improvement.

The discovery of noncoding RNAs (ncRNAs) including short microRNAs, long ncRNAs and circular RNAs has broaden our knowledge about mammalian genomes and transcriptomes. A growing number of evidence on aberrantly regulated ncRNAs in cardiovascular diseases has indicated that ncRNAs are critical contributors to cardiovascular pathophysiology. Moreover, multiple recent studies have reported that ncRNAs can be detected in the bloodstream that differs between health subjects and diseased patients and some of them are remarkably stable. Although our knowledge about the origin and function of the circulating ncRNAs is still limited, these molecules have been regarded as promising noninvasive biomarker for risk stratification, diagnosis and prognosis of various cardiovascular diseases. In this chapter, we have described biological characteristics of circulating ncRNAs and discussed current trends and future prospects for the usage of circulating ncRNAs as biomarkers for common cardiovascular diseases.

The discovery of noncoding RNAs (ncRNAs) including short microRNAs, long ncRNAs and circular RNAs has broaden our knowledge about mammalian genomes and transcriptomes. A growing number of evidence on aberrantly regulated ncRNAs in cardiovascular diseases has indicated that ncRNAs are critical contributors to cardiovascular pathophysiology. Moreover, multiple recent studies have reported that ncRNAs can be detected in the bloodstream that differs between health subjects and diseased patients and some of them are remarkably stable. Although our knowledge about the origin and function of the circulating ncRNAs is still limited, these molecules have been regarded as promising noninvasive biomarker for risk stratification, diagnosis and prognosis of various cardiovascular diseases. In this chapter, we have described biological characteristics of circulating ncRNAs and discussed current trends and future prospects for the usage of circulating ncRNAs as biomarkers for common cardiovascular diseases.

Most of the developing countries are in need of sanitary toilets due to insufficient supporting facilities and proven technology mainly on disposal of fecal sewage. A microbial fuel cell (MFC)-microbial electrolytic cell (MEC) coupling with an anaerobic baffle reactor (ABR) was used to realize simultaneous removal of nitrogen and carbon in fecal sewage and complete energy recycling. Configuration and rapid start-up of the ABR-MFC-MEC process treating fecal sewage was systematically studied. Results showed that the application of an external voltage of 0.5 V can shorten the start-up time and improve hydrogen production rate to 3.42 × 10−3 m3-H2/m3/d in the MEC unit, where the double-chamber MFC can drive MEC completing the synchronous coupling start-up. In the single and double chamber systems, bio-electrochemical processes both enhanced shock resistance capacity of the whole ABR-MFC-MEC process during coupled operation, with chemical oxygen demand (COD) removal rates of 99.2% and 98.9% for the single and double chamber systems respectively. Based on results of biological analysis, the coupled system has a distinct selective effect on microbial population and each unit has high microbial diversity to enhance the stability and resistance of the whole system for treatment of feces and urine., Graphical abstract Unlabelled Image, Highlights • A novel coupled bio-electrochemical process was developed to treat fecal sewage. • Optimal configuration and start-up mode of the coupled process were determined. • 0.5 V was determined as the threshold voltage shortening start-up time. • The coupling mechanism of the combined process were investigated.