Interferon-α stimulates DExH-box helicase 58 to prevent hepatocyte ferroptosis.

BACKGROUND: Liver ischemia/reperfusion (I/R) injury is usually caused by hepatic inflow occlusion during liver surgery, and is frequently observed during war wounds and trauma. Hepatocyte ferroptosis plays a critical role in liver I/R injury, however, it remains unclear whether this process is controlled or regulated by members of the DEAD/DExH-box helicase (DDX/DHX) family. METHODS: The expression of DDX/DHX family members during liver I/R injury was screened using transcriptome analysis. Hepatocyte-specific Dhx58 knockout mice were constructed, and a partial liver I/R operation was performed. Single-cell RNA sequencing (scRNA-seq) in the liver post I/R suggested enhanced ferroptosis by Dhx58hep-/-. The mRNAs and proteins associated with DExH-box helicase 58 (DHX58) were screened using RNA immunoprecipitation-sequencing (RIP-seq) and IP-mass spectrometry (IP-MS). RESULTS: Excessive production of reactive oxygen species (ROS) decreased the expression of the IFN-stimulated gene Dhx58 in hepatocytes and promoted hepatic ferroptosis, while treatment using IFN-α increased DHX58 expression and prevented ferroptosis during liver I/R injury. Mechanistically, DHX58 with RNA-binding activity constitutively associates with the mRNA of glutathione peroxidase 4 (GPX4), a central ferroptosis suppressor, and recruits the m6A reader YT521-B homology domain containing 2 (YTHDC2) to promote the translation of Gpx4 mRNA in an m6A-dependent manner, thus enhancing GPX4 protein levels and preventing hepatic ferroptosis. CONCLUSIONS: This study provides mechanistic evidence that IFN-α stimulates DHX58 to promote the translation of m6A-modified Gpx4 mRNA, suggesting the potential clinical application of IFN-α in the prevention of hepatic ferroptosis during liver I/R injury.

Anchoring Ultrafine ß-Mo2C Clusters Inside Porous Co-NC Using MOFs for Electric-Powered Coproduction of Valuable Chemicals.

Electroredox of organics provides a promising and green approach to producing value-added chemicals. However, it remains a grand challenge to achieve high selectivity of desired products simultaneously at two electrodes, especially for non-isoelectronic transfer reactions. Here a porous heterostructure of Mo2C@Co-NC is successfully fabricated, where subnanometre ß-Mo2C clusters (<1 nm, ≈10 wt%) are confined inside porous Co, N-doped carbon using metalorganic frameworks. It is found that Co species not only promote the formation of ß-Mo2C but also can prevent it from oxidation by constructing the heterojunctions. As noted, the heterostructure achieves >96% yield and 92% Faradaic efficiency (FE) for aldehydes in anodic alcohol oxidation, as well as >99.9% yield and 96% FE for amines in cathodal nitrocompounds reduction in 1.0 M KOH. Precise control of the reaction kinetics of two half-reactions by the electronic interaction between ß-Mo2C and Co is a crucial adjective. Density functional theory (DFT) gives in-depth mechanistic insight into the high aldehyde selectivity. The work guides authors to reveal the electrooxidation nature of Mo2C at a subnanometer level. It is anticipated that the strategy will provide new insights into the design of highly effective bifunctional electrocatalysts for the coproduction of more complex fine chemicals.

A pulmonary source of infection in patients with sepsis-associated acute kidney injury leads to a worse outcome and poor recovery of kidney function.

BACKGROUND: Hospital mortality rates are higher among patients with sepsis-associated acute kidney injury (SA-AKI) than among patients with sepsis. However, the pathogenesis underlying SA-AKI remains unclear. We hypothesized that the source of infection affects development of SA-AKI. We aim to explore the relationship between the anatomical source of infection and outcome in patients with SA-AKI. METHODS: Between January 2013 and January 2018, 113 patients with SA-AKI admitted to our Emergency Center were identified and divided into two groups: those with pulmonary infections and those with other sources of infection. For each patient, we collected data from admission until either discharge or death. We also recorded the clinical outcome after 90 days for the discharged patients. RESULTS: The most common source of infection was the lung (52/113 cases, 46%), followed by gastrointestinal (GI) (25/113 cases, 22.1%) and urinary (22/113, 19.5%) sources. Our analysis showed that patients with SA-AKI had a significantly worse outcome (30/52 cases, P<0.001) and poorer kidney recovery (P=0.015) with pulmonary sources of infection than those infected by another source. Data also showed that patients not infected by a pulmonary source more likely experienced shock (28/61 cases, P=0.037). CONCLUSION: This study demonstrated that the source of infection influenced the outcome of SA-AKI patients in an independent manner. Lung injury may influence renal function in an as-yet undetermined manner as the recovery of kidney function was poorer in SA-AKI patients with a pulmonary source of infection.

[Characteristic of Benzo[a]pyrene Anaerobic Degradation by Phenol Co-substrate and Microbial Communities from Two Types of Sludge].

Benzo[a]pyrene (BaP) is a typical representative of PAHs in coking wastewater and priority-controlled pollutants in the coking industry; its response characteristics with microorganisms and the methods to promote its degradation are worth studying. On the other hand, because the inoculated sludge for the adjustment and operation of newly-constructed coking wastewater treatment plants comes from municipal sludge or other coking plants, currently, the study of the microbial properties of different sludges', sludge availability, and the conditions that influence these properties are lacking. On account of the above perspectives, an experiment to study and compare the durability of municipal sludge and coking sludge, and their ability to degrade BaP was carried out. An anaerobic reactor was selected for the experiment and anaerobic-activated sludges were collected from a coking wastewater processing unit and a municipal wastewater plant. Then, 10 mg·L-1 of BaP alone and BaP with phenol as a co-metabolic carbon source was added to the coking and municipal sludge samples, respectively, for comparison experiments to study the microbial degradation of BaP and its dynamics. Moreover, high-throughput sequencing technology was also used to analyze the changes in the microbial community structure before and after the degradation experiment. The results showed that:① Both sludges were capable of degrading BaP, but municipal sludge showed a higher degradation efficiency than coking sludge; ② Adding phenol as co-substrate promoted the biodegradation of BaP in both sludges. When BaP was the sole carbon source, the half-life of BaP in the two sludges was 155.41 d and 116.3 d respectively. After the addition of phenol, the half-life was reduced to 81.25 d and 38.44 d, respectively; ③ According to the analysis of the microbial community structure, the community composition in both sludges changed markedly. Moreover, the microbial community in the municipal sludge showed a more evident change than that of the coking sludge. In the coking sludge, the dominant bacteria community changed a little after acclimation, most of the observed bacteria were previously reported common PAH-degrading strains. In contrast, the dominant bacteria community in the municipal sludge varied greatly after acclimation, and the most abundant bacteria were not common PAH-degrading strains. In addition, some frequently reported PAHs-degrading bacteria such as Bacillus sp., Pseudomonas, Achromobacter, and Sphingomonas sp., were identified in both the sludges and were present in high abundance. The results indicated that municipal sludge utilized BaP more actively than coking sludge; this phenomenon can be explained by the fact that municipal sludge contained a higher diversity of microbes that were involved in the degradation of BaP. Furthermore, the presence of phenol promoted the degradation of PAHs like BaP. Therefore, we proposed that the PAHs in coking sludge discharge might be reduced by the addition phenol and municipal wastewater.

[Aerobic Degradation and Microbial Community Succession of Coking Wastewater with Municipal Sludge].

Coking wastewater is a typical industrial wastewater with high toxicity. Its treatment with biological processes is often challenging because it contains constituents inhibiting microbial activity. To study the inhibitory effect and possible acclimation of microbes in coking wastewater treatment, municipal sludge was inoculated into coking wastewater. Time-dependent concentrations of COD, phenol, ammonia nitrogen, and thiocyanide in coking wastewater were analyzed. The microbial community structure was investigated by the Illumina high-throughput sequencing technology during inoculation. The results showed that COD began to decrease after 16 h and 97.1% of phenol disappeared after 40 h. Thiocyanide began to degrade at 72 h and was undetectable after 96 h. Accordingly, the concentration of ammonia increased as the thiocyanide concentrations decreased. High-throughput pyrosequencing analysis showed that the microbial community structure and species richness varied at different culture stages. In the stage of phenol degradation, the abundance of Acinetobacter and Pseudomonas increased rapidly; the species richness was 13.04% of the community at 48 h. In the stage of thiocyanate degradation, Sphingobacterium,Brevundimonas,Lysobacter, and Chryseobacterium were the dominant bacteria and were 16.13% of the community at 96 h. At 144 h, Fluviicola,Stenotrophomonas, and Thiobacillus became the dominant species and were 22.45% of the community abundance. The results showed that municipal sludge can rapidly overcome the toxicity of coking wastewater because the pollutants are degraded rapidly. The microbial community structure changed as wastewater components were degraded. Environmental factors and the competition among bacteria played a key role in microbial community succession.