Iron-based autotrophic denitrification driven by sponge iron for nitrite removal in an anaerobic bioreactor: Effect of iron and carbon source.

The study investigated the denitrification effect of the iron autotrophic denitrification process for removing nitrite under anaerobic conditions, utilizing sponge iron as the electron donor. When the C/N ratio equaled 1, defined as the ratio of chemical oxygen demand to total nitrogen (TN), and the influent nitrite nitrogen (NO2--N) was at 80 mg/L, the average steady-state TN effluent concentration of this system was 41.94 mg/L during the 79-day experiment. The TN value exhibited a significant decrease compared to both the sponge iron system (68.69 mg/L) and the carbon source system (56.50 mg/L). Sponge iron is beneficial for providing an electron donor and ensuring an anaerobic system, fostering an environment that promotes microorganism growth while effectively inhibiting the conversion of nitrite to nitrate. In addition, carbon sources play a vital role in ensuring microorganism growth and reproduction, thereby aiding in TN removal. The optimal parameters based on the effectiveness of TN removal in the iron autotrophic denitrification system were determined to be s-Fe0 dosage of 30 g/L and C/N = 1.5. These results suggest that the iron autotrophic denitrification process, driven by sponge iron, can effectively remove nitrite under anaerobic conditions.

Pathogenesis-Guided Rational Engineering of Nanotherapies for the Targeted Treatment of Abdominal Aortic Aneurysm by Inhibiting Neutrophilic Inflammation.

Abdominal aortic aneurysm (AAA) remains a fatal disease in the elderly. Currently, no drugs can be clinically used for AAA therapy. Considering the pivotal role of neutrophils in the pathogenesis of AAA, herein we propose the targeted therapy of AAA by site-specifically regulating neutrophilic inflammation. Based on a luminol-conjugated α-cyclodextrin material (LaCD), intrinsically anti-inflammatory nanoparticles (NPs) were engineered by simple nanoprecipitation, which were examined as a nanotherapy (defined as LaCD NP). After efficient accumulation in the aneurysmal aorta and localization in pathologically relevant inflammatory cells in rats with CaCl2-induced AAA, LaCD NP significantly alleviated AAA progression, as implicated by the decreased aortic expansion, suppressed elastin degradation, inhibited calcification, and improved structural integrity of the abdominal aorta. By functionalizing LaCD NP with alendronate, a calcification-targeting moiety, the in vivo aneurysmal targeting capability of LaCD NP was considerably enhanced, thereby affording significantly potentiated therapeutic outcomes in AAA rats. Mechanistically, LaCD NP can effectively inhibit neutrophil-mediated inflammatory responses in the aneurysmal aorta. Particularly, LaCD NP potently attenuated the formation of neutrophil extracellular traps (NETs), thereby suppressing NETs-mediated pro-inflammatory events and NETosis-associated negative effects responsible for AAA progression. Consequently, we demonstrated the effectiveness and underlying mechanisms of anti-NETosis nanotherapies for the targeted treatment of AAA. Our findings provide promising insights into discovering precision therapies for AAA and other inflammatory vascular diseases.

Functions and mechanisms of sponge iron-mediated multiple metabolic processes in anaerobic ammonium oxidation.

Sponge iron (SI) is a promising material for nitrogen removal from wastewater. This study reveals the potential functions and mechanisms of SI-mediated multiple metabolic processes in the nitrogen removal of Anammox. The results showed that although the SI application prolonged the start-up time of the reactor, achieved efficient and stable nitrogen removal after a successful start-up. The total nitrogen removal efficiency of the SI-Anammox system (92.62%) was 13.30% higher than that of R0 without SI (79.32%). The increase in nitrogen removal performance was accompanied by an increase in SAA and EPS content. Further microbial analysis showed significant enrichment of functional microorganisms, such as Candidatus_Brocadia, Nitrosomonas, Ellin6067, and Nitrospira. Multi-omics evidence suggests that efficient nitrogen removal is ultimately attributable to the enhancement of the specific key Fe- and N-functional genes in Anammox.

Reactive Oxygen Species-Responsive Transformable and Triple-Targeting Butylphthalide Nanotherapy for Precision Treatment of Ischemic Stroke by Normalizing the Pathological Microenvironment.

High potency and safe therapies are still required for ischemic stroke, which is a leading cause of global death and disability. Herein, a reactive oxygen species (ROS)-responsive, transformable, and triple-targeting dl-3-n-butylphthalide (NBP) nanotherapy was developed for ischemic stroke. To this end, a ROS-responsive nanovehicle (OCN) was first constructed using a cyclodextrin-derived material, which showed considerably enhanced cellular uptake in brain endothelial cells due to notably reduced particle size, morphological transformation, and surface chemistry switching upon triggering via pathological signals. Compared to a nonresponsive nanovehicle, this ROS-responsive and transformable nanoplatform OCN exhibited a significantly higher brain accumulation in a mouse model of ischemic stroke, thereby affording notably potentiated therapeutic effects for the nanotherapy derived from NBP-containing OCN. For OCN decorated with a stroke-homing peptide (SHp), we found significantly increased transferrin receptor-mediated endocytosis, in addition to the previously recognized targeting capability to activated neurons. Consistently, the engineered transformable and triple-targeting nanoplatform, i.e., SHp-decorated OCN (SON), displayed a more efficient distribution in the injured brain in mice with ischemic stroke, showing considerable localization in endothelial cells and neurons. Furthermore, the finally formulated ROS-responsive transformable and triple-targeting nanotherapy (NBP-loaded SON) demonstrated highly potent neuroprotective activity in mice, which outperformed the SHp-deficient nanotherapy at a 5-fold higher dose. Mechanistically, our bioresponsive, transformable, and triple-targeting nanotherapy attenuated the ischemia/reperfusion-induced endothelial permeability and improved dendritic remodeling and synaptic plasticity of neurons in the injured brain tissue, thereby promoting much better functional recovery, which were achieved by efficiently enhancing NBP delivery to the ischemic brain tissue, targeting injured endothelial cells and activated neurons/microglial cells, and normalizing the pathological microenvironment. Moreover, preliminary studies indicated that the ROS-responsive NBP nanotherapy displayed a good safety profile. Consequently, the developed triple-targeting NBP nanotherapy with desirable targeting efficiency, spatiotemporally controlled drug release performance, and high translational potential holds great promise for precision therapy of ischemic stroke and other brain diseases.

Effects of sponge iron dosage on nitrogen removal performance and microbial community structure in sequencing batch reactors.

The application of sponge iron (SI) carriers can improve the biochemical treatment performance of sequencing batch reactors (SBR) during wastewater treatment. This study used SBR reactors to explore the effects of SI dosage on the nitrogen removal performance and reactor stability and microbial community structure under low temperature and ultra-low load. In contrast to conventional SBR, the average removal rate of total nitrogen (TN) in the biological sponge iron system (BSIS) was increased by 5.38 % for 45 g/L, 18.93 % for 90 g/L, and 13.52 % for 135 g/L, respectively. The nitrogen removal performance and reactor stability showed the best performance under the SI dosage of 90 g/L. The addition of SI formed the anaerobic-anoxic-aerobic microenvironments, which facilitate the propagation of denitrifying bacteria (Saccharimonadales, Hydrogenophaga) and iron bacteria (Rhodoferax and Acinetobacter) in the BSIS. This study provides a new insight on the application of SI in the wastewater treatment.

Autotrophic denitrification using Fe(II) as an electron donor: A novel prospective denitrification process.

As a newly identified nitrogen loss pathway, the nitrate-dependent ferrous oxidation (NDFO) process is emerging as a research hotspot in the field of low carbon to nitrogen ratio (C/N) wastewater treatment. This review article provides an overview of the NDFO process and summarizes the functional microorganisms associated with NDFO from different perspectives. The potential mechanisms by which external factors such as influent pH, influent Fe(II)/N (mol), organic carbon, and chelating agents affect NDFO performance are also thoroughly discussed. As the electron-transfer mechanism of the NDFO process is still largely unknown, the extensive chemical Fe(II)-oxidizing nitrite-reducing pathway (NDFOchem) of the NDFO process is described here, and the potential enzymatic electron transfer mechanisms involved are summarized. On this basis, a three-stage electron transfer pathway applicable to low C/N wastewater is proposed. Furthermore, the impact of Fe(III) mineral products on the NDFO process is revisited, and existing crusting prevention strategies are summarized. Finally, future challenges facing the NDFO process and new research directions are discussed, with the aim of further promoting the development and application of the NDFO process in the field of nitrogen removal.

A Multi-Bioactive Nanomicelle-Based "One Stone for Multiple Birds" Strategy for Precision Therapy of Abdominal Aortic Aneurysms.

Abdominal aortic aneurysm (AAA) remains a lethal aortic disease in the elderly. Currently, no effective drugs can be clinically applied to prevent the development of AAA. Herein, a "one stone for multiple birds" strategy for AAA therapy is reported. As a proof of concept, three bioactive conjugates are designed and synthesized, which can assemble into nanomicelles. Cellularly, these nanomicelles significantly inhibit migration and activation of inflammatory cells as well as protect vascular smooth muscle cells (VSMCs) from induced oxidative stress, calcification and apoptosis, with the best effect for nanomicelles (TPTN) derived from a conjugate defined as TPT. After intravenous delivery, TPTN efficiently accumulates in the aneurysmal tissue of AAA rats, showing notable distribution in neutrophils, macrophages and VSMCs, all relevant to AAA pathogenesis. Whereas three examined nanomicelles effectively delay expansion of AAA in rats, TPTN most potently prevents AAA growth by simultaneously normalizing the pro-inflammatory microenvironment and regulating multiple pathological cells. TPTN is effective even at 0.2 mg kg-1 . Besides, TPTN can function as a bioactive nanoplatform for site-specifically delivering and triggerably releasing anti-aneurysmal drugs, affording synergistic therapeutic effects. Consequently, TPTN is a promising multi-bioactive nanotherapy and bioresponsive targeting delivery nanocarrier for effective therapy of AAA and other inflammatory vascular diseases.

Targeted Treatment of Ischemic Stroke by Bioactive Nanoparticle-Derived Reactive Oxygen Species Responsive and Inflammation-Resolving Nanotherapies.

Stroke is a primary cause of death and disability worldwide, while effective and safe drugs remain to be developed for its clinical treatment. Herein, we report bioactive nanoparticle-derived multifunctional nanotherapies for ischemic stroke, which are engineered from a pharmacologically active oligosaccharide material (termed as TPCD) prepared by covalently conjugating a radical-scavenging compound (Tempol) and a hydrogen-peroxide-eliminating moiety of phenylboronic acid pinacol ester (PBAP) on ß-cyclodextrin. Of note, combined functional moieties of Tempol and PBAP on ß-cyclodextrin contribute to antioxidative and anti-inflammatory activities of TPCD. Cellularly, TPCD nanoparticles (i.e., TPCD NPs) reduced oxygen-glucose deprivation-induced overproduction of oxidative mediators, increased antioxidant enzyme expression, and suppressed microglial-mediated inflammation, thereby inhibiting neuronal apoptosis. After intravenous (i.v.) delivery, TPCD NPs could efficiently accumulate at the cerebral ischemic injury site of mice with middle cerebral artery occlusion (MCAO), showing considerable distribution in cells relevant to the pathogenesis of stroke. Therapeutically, TPCD NPs significantly decreased infarct volume and accelerated recovery of neurological function in MCAO mice. Mechanistically, efficacy of TPCD NPs is achieved by its antioxidative, anti-inflammatory, and antiapoptotic effects. Furthermore, TPCD NPs can function as a reactive oxygen species labile nanovehicle to efficiently load and triggerably release an inflammation-resolving peptide Ac2-26, giving rise to an inflammation-resolving nanotherapy (i.e., ATPCD NP). Compared to TPCD NP, ATPCD NP demonstrated notably enhanced in vivo efficacies, largely resulting from its additional inflammation-resolving activity. Consequently, TPCD NP-derived nanomedicines can be further developed as promising targeted therapies for stroke and other inflammation-associated cerebrovascular diseases.

Pulmonary circulation-mediated heart targeting for the prevention of heart failure by inhalation of intrinsically bioactive nanoparticles.

Heart failure is a serious clinical and public health problem. Currently there is an unmet demand for effective therapies for heart failure. Herein we reported noninvasive inhalation delivery of nanotherapies to prevent heart failure. Methods: A reactive oxygen species (ROS)-scavenging material (TPCD) was synthesized, which was processed into antioxidative and anti-inflammatory nanoparticles (i.e., TPCD NP). By decoration with a mitochondrial-targeting moiety, a multilevel targeting nanotherapy TTPCD NP was engineered. Pulmonary accumulation of inhaled TPCD NP and underlying mechanisms were examined in mice. In vivo efficacies of nanotherapies were evaluated in mice with doxorubicin (DOX)-induced cardiomyopathy. Further, an antioxidative, anti-inflammatory, and pro-resolving nanotherapy (i.e., ATTPCD NP) was developed, by packaging a peptide Ac2-26. In vitro and in vivo efficacies of ATTPCD NP were also evaluated. Results: TPCD NP alleviated DOX-induced oxidative stress and cell injury by internalization in cardiomyocytes and scavenging overproduced ROS. Inhaled TPCD NP can accumulate in the heart of mice by transport across the lung epithelial and endothelial barriers. Correspondingly, inhaled TPCD NP effectively inhibited DOX-induced heart failure in mice. TTPCD NP showed considerably enhanced heart targeting capability, cellular uptake efficiency, and mitochondrial localization capacity, thereby potentiating therapeutic effects. Notably, TPCD NP can serve as bioactive and ROS-responsive nanovehicles to achieve combination therapy with Ac2-26, affording further enhanced efficacies. Importantly, inhaled TPCD NP displayed good safety at a dose 5-fold higher than the efficacious dose. Conclusions: Inhalation delivery of nanoparticles is an effective, safe, and noninvasive strategy for targeted treatment of heart diseases. TPCD NP-based nanotherapies are promising drugs for heart failure and other acute/chronic heart diseases associated with oxidative stress.