Performance, microbial growth and community interactions of iron-dependent denitrification in freshwaters

Iron-dependent denitrification is a safe and promising technology for nitrogen removal in freshwaters. However, the understanding of microbial physiology and interactions during the process was limited. Denitrifying systems inoculated with freshwater samples were operated with and without iron(II) at a low C/N ratio for 54 days. Iron addition improved nitrogen removal. Batch experiments confirmed that microbially mediated reaction rather than abiotic reaction dominated during the process. Metagenomics recovered genomes of the five most abundant microorganisms, which accounted for over 99% of the community in every triplicate of the iron-based system. Based on codon usage bias, all of them were fast-growing organisms. The total abundance of fast-growing organisms was 38% higher in the system with iron than in the system without iron. Notably, the most abundant organism Diaphorobacter did not have enzymes for asparagine and aspartate biosynthesis, whereas Rhodanobacter could not produce serine and cobalamin. Algoriphagus and Areminomonas lost synthesis enzymes for more amino acids and vitamins. However, they could always obtain these growth-required substances from another microorganism in the community. The two-partner relationship minimized the limitation on microbial reproduction and increased community stability. Our results indicated that iron addition improved nitrogen removal by supplying electron donors, promoting microbial growth, and building up syntrophic interactions among microorganisms with timely communications. The findings provided new insights into the process, with implications for freshwater remediation

A high precision, fast response, and low power consumption in situ optical fiber chemical pCO(2) sensor

A sensor system suitable for monitoring changes in partial pressure of carbon dioxide (pCO(2)) in surface seawater or in the atmosphere has been developed. Surface seawater samples are pumped into a PVC tube enclosing an inner Teflon AF tube, which served as a long pathlength gas-permeable liquid-core waveguide for spectrophotometry. The Teflon cell contains a pH-sensitive indicator-buffer solution consisting of bromothymol blue (BTB) and sodium carbonate. Carbon dioxide in the sample diffuses into the indicator-buffer solution to reach equilibrium, resulting in pH changes, which are detected by changes in the absorbance of BTB at wavelengths of 620 and 434 nm. The pCO(2) in the sample is then derived from the pH change. The sensor has a response time of 2 min at the 95% equilibrium value and a measurement precision of 0.26-0.37% in the range 200-800 mu atm pCO(2). This chemical sensor takes advantage of a combination of long pathlength, multiple wavelength detection, indicator solution renewal, and in situ automatic control technology, and has the feature of low power consumption (the average being similar to 4W with a peak of similar to 8 W). (C) 2008 Elsevier B.V. All rights reserved

Targeting TANK-binding kinase 1 attenuates painful diabetic neuropathy via inhibiting microglia pyroptosis

Abstract Background Painful diabetic neuropathy (PDN) is closely linked to inflammation, which has been demonstrated to be associated with pyroptosis. Emerging evidence has implicated TANK-binding kinase 1 (TBK1) in various inflammatory diseases. However, it remains unknown whether activated TBK1 causes hyperalgesia via pyroptosis. Methods PDN mice model of type 1 or type 2 diabetic was induced by C57BL/6J or BKS-DB mice with Lepr gene mutation. For type 2 diabetes PDN model, TBK1-siRNA, Caspase-1 inhibitor Ac-YVAD-cmk or TBK1 inhibitor amlexanox (AMX) were delivered by intrathecal injection or intragastric administration. The pain threshold and plantar skin blood perfusion were evaluated through animal experiments. The assessments of spinal cord, dorsal root ganglion, sciatic nerve, plantar skin and serum included western blotting, immunofluorescence, ELISA, and transmission electron microscopy. Results In the PDN mouse model, we found that TBK1 was significantly activated in the spinal dorsal horn (SDH) and mainly located in microglia, and intrathecal injection of chemically modified TBK1-siRNA could improve hyperalgesia. Herein, we described the mechanism that TBK1 could activate the noncanonical nuclear factor κB (NF-κB) pathway, mediate the activation of NLRP3 inflammasome, trigger microglia pyroptosis, and ultimately induce PDN, which could be reversed following TBK1-siRNA injection. We also found that systemic administration of AMX, a TBK1 inhibitor, could effectively improve peripheral nerve injury. These results revealed the key role of TBK1 in PDN and that TBK1 inhibitor AMX could be a potential strategy for treating PDN. Conclusions Our findings revealed a novel causal role of TBK1 in pathogenesis of PDN, which raises the possibility of applying amlexanox to selectively target TBK1 as a potential therapeutic strategy for PDN

Targeting the MCP‐GPX4/HMGB1 Axis for Effectively Triggering Immunogenic Ferroptosis in Pancreatic Ductal Adenocarcinoma

Abstract Induction of ferroptosis can inhibit cancer cells in vitro, however, the role of ferroptosis in treatment in vivo is controversial. The immunosuppressive cells activated by the ferroptotic tumor cells can promote the growth of residual tumor cells, hindering the application of ferroptosis stimulation in tumor treatment. In this study, a new strategy is aimed to be identified for effectively triggering immunogenic ferroptosis in pancreatic ductal adenocarcinoma (PDAC) and simultaneously stimulating antitumor immune responses. Toward this, several molecular and biochemical experiments are performed using patient‐derived organoid models and a KPC mouse model (LSL‐KrasG12D/+, LSL‐Trp53R172H/+, Pdx‐1‐Cre). It is observed that the inhibition of macrophage‐capping protein (MCP) suppressed the ubiquitin fold modifier (UFM)ylation of pirin (PIR), a newly identified substrate of UFM1, thereby decreasing the transcription of GPX4, a marker of ferroptosis, and promoting the cytoplasmic transportation of HMGB1, a damage‐associated molecular pattern. GPX4 deficiency triggered ferroptosis, and the pre‐accumulated cytosolic HMGB1 is released rapidly. This altered release pattern of HMGB1 facilitated the pro‐inflammatory M1‐like polarization of macrophages. Thus, therapeutic inhibition of MCP yielded dual antitumor effects by stimulating ferroptosis and activating antitumor pro‐inflammatory M1‐like macrophages. The nanosystem developed for specifically silencing MCP is a promising tool for treating PDAC