Cpd-A1 alleviates acute kidney injury by inhibiting ferroptosis.

Acute kidney injury (AKI) is defined as sudden loss of renal function characterized by increased serum creatinine levels and reduced urinary output with a duration of 7 days. Ferroptosis, an iron-dependent regulated necrotic pathway, has been implicated in the progression of AKI, while ferrostatin-1 (Fer-1), a selective inhibitor of ferroptosis, inhibited renal damage, oxidative stress and tubular cell death in AKI mouse models. However, the clinical translation of Fer-1 is limited due to its lack of efficacy and metabolic instability. In this study we designed and synthesized four Fer-1 analogs (Cpd-A1, Cpd-B1, Cpd-B2, Cpd-B3) with superior plasma stability, and evaluated their therapeutic potential in the treatment of AKI. Compared with Fer-1, all the four analogs displayed a higher distribution in mouse renal tissue in a pharmacokinetic assay and a more effective ferroptosis inhibition in erastin-treated mouse tubular epithelial cells (mTECs) with Cpd-A1 (N-methyl-substituted-tetrazole-Fer-1 analog) being the most efficacious one. In hypoxia/reoxygenation (H/R)- or LPS-treated mTECs, treatment with Cpd-A1 (0.25 µM) effectively attenuated cell damage, reduced inflammatory responses, and inhibited ferroptosis. In ischemia/reperfusion (I/R)- or cecal ligation and puncture (CLP)-induced AKI mouse models, pre-injection of Cpd-A1 (1.25, 2.5, 5 mg·kg-1·d-1, i.p.) dose-dependently improved kidney function, mitigated renal tubular injury, and abrogated inflammation. We conclude that Cpd-A1 may serve as a promising therapeutic agent for the treatment of AKI.

Biochar enhanced the stability of toluene removal in extracted groundwater amended with nitrate under microaerobic conditions.

Groundwater pollution caused by the leakage of petroleum and various fuel oils is becoming a serious environmental problem. In this study, carbon-based materials including biochar and hydrochar were applied to investigate the effects of additives on the toluene removal in the extracted groundwater under microaerobic condition with the addition of nitrate. Biochar and hydrochar could adsorb toluene, and thus enhance the toluene removal in the system. The toluene removal efficiency was 8.2-8.9 mg/(g·h) at the beginning, and then decreased with time in the control and the hydrochar treatment, while it remained the stable values in the biochar treatment, owing to the fact that biochar could reduce the NO3--N loss by partial denitrification. Moreover, biochar could prompt the growth of toluene-degrading bacteria including Thauera, Rhodococcus, Ideonella and Denitratisoma, which had the capability of denitrification. However, hydrochar could stimulated the growth of denitrifiers without toluene-degrading capacity including Candidatus Competibacter and Ferrovibrio, which might play a key role in the partial denitrification of the system. The findings are helpful for developing remediation techniques of contaminated groundwater.

Adsorption Mechanism and Regeneration Performance of Calcined Zeolites for Hydrogen Sulfide and Its Application.

Hydrogen sulfide (H2S) is a very toxic, acidic, and odorous gas. In this study, a calcined zeolite was used to investigate the adsorption performance of H2S. Among particle size, calcination temperature and time calcination temperature and time had significant effects on the adsorption capacity of H2S on the zeolite. The optimal calcination conditions for the zeolite were 332 °C, 1.8 h, and 10-20 mm size, and the maximum adsorption capacity of H2S was approximately 6219 mg kg-1. Calcination could broaden the channels, remove the adsorbed gases and impurities on the surface of zeolites, and increase the average pore size and point of zero net charge. As the zeolite adsorbed to saturation, it could be regenerated at the temperatures between 200 and 350 °C for 0.5 h. Compared with the natural zeolite, the adsorption capacities of dimethyl disulfide, dimethyl sulfide, toluene, CH3SH, CS2, CO2, and H2S were significantly higher on the calcined zeolite, while the adsorption capacity of CH4 was lower on the calcined zeolite. A gas treatment system by a temperature swing adsorption-regeneration process on honeycomb rotors with calcined zeolites was proposed. These findings are helpful for developing techniques for removing gas pollutants such as volatile sulfur compounds and volatile organic compounds to purify biogas and to limited toxic concentrations in the working environment.

Selection of Peptide-Bismuth Bicycles Using Phage Display.

Cysteine conjugation is widely used to constrain phage displayed peptides for the selection of cyclic peptides against specific targets. In this study, the nontoxic Bi3+ ion was used as a cysteine conjugation reagent to cross-link peptide libraries without compromising phage infectivity. We constructed a randomized 3-cysteine peptide library and cyclized it with Bi3+, followed by a selection against the maltose-binding protein as a model target. Next-generation sequencing of selection samples revealed the enrichment of peptides containing clear consensus sequences. Chemically synthesized linear and Bi3+ cyclized peptides were used for affinity validation. The cyclized peptide showed a hundred-fold better affinity (0.31 ± 0.04 µM) than the linear form (39 ± 6 µM). Overall, our study proved the feasibility of developing Bi3+ constrained bicyclic peptides against a specific target using phage display, which would potentially accelerate the development of new peptide-bismuth bicycles for therapeutic or diagnostic applications.

Effects of Fe-modified digestate hydrochar at different hydrothermal temperatures on anaerobic digestion of swine manure.

Hydrothermal carbonization temperature is a key factor in controlling the physico-chemical properties of hydrochar and affecting its function. In this study, effects of hydrochar and Fe-modified hydrochar (Fe-HC) prepared at 180 °C (180C-Fe), 220 °C (220C-Fe) and 260 °C (260C-Fe) on anaerobic digestion (AD) performance of swine manure was investigated. Among the three Fe-HCs, 220C-Fe had the highest amount of Fe and Fe2+ on the surface. The relative methane production of control reached 174 %-189 % in the 180C-Fe and 220C-Fe treatments between days 11 and 12. The degradation efficiency of swine manure was highest in the 220C-Fe treatment (61.3 %), which was 14.8 % higher than in the control. Fe-HC could act as an electron shuttle, stimulate the coenzyme F420 formation, increase the relative abundance of Methanosarcina and promote electron transport for acetotrophic methanogenesis in the AD. These findings are helpful for designing an efficient process for treating swine manure and utilizing digestate.

Metagenomic insights into phenanthrene biodegradation in electrical field-governed biofilms for groundwater bioremediation.

Electrical fields (EFs)-assisted in-situ bioremediation of petroleum-contaminated groundwater, such as polycyclic aromatic hydrocarbons, has drawn increasing attention. However, the long-term stability, the EFs influence, and metabolic pathways are still poorly understood, hindering the further development of robust technology design. Herein, a series of EFs was applied to the phenanthrene-contaminated groundwater, and the corresponding system performance was investigated. The highest removal capacity of phenanthrene (phe) (7.63 g/(m3·d)) was achieved with EF_0.8 V biofilm at a hydrolytic retention time of 0.5 d. All the biofilms with four EFs exhibited a high removal efficiency of phe over 80% during a 100-d continuous-flow operation. Intermediates analysis revealed the main pathways of phe degradation: phthalate and salicylate via hydroxylation, methylation, carboxylation, and ring cleavage steps. Synergistic effects between phe-degraders (Dechloromonas), fermentative bacteria (Delftia), and electroactive microorganisms (Geobacter) were the main contributors to the complete phe mineralization. Genes encoding various proteins of methyl-accepting (mcp), response regulator (cheABDRY), and type IV pilus (pilABCMQV) were dominant, revealing the importance of cell motility and extracellular electron transfer. Metagenomics analysis unveiled phe-degrading genes, including ring reduction enzymes (bamBCDE), carboxylase of aromatics (ubiD), and methyltransferase protein (ubiE, pcm). These findings offered a molecular understanding of refractory organics' decompositions in EFs-governed biotechnology.

Aurantiamide mitigates acute kidney injury by suppressing renal necroptosis and inflammation via GRPR-dependent mechanism.

Acute kidney injury (AKI) manifests as a clinical syndrome characterised by the rapid accumulation of metabolic wastes, such as blood creatinine and urea nitrogen, leading to a sudden decline in renal function. Currently, there is a lack of specific therapeutic drugs for AKI. Previously, we identified gastrin-releasing peptide receptor (GRPR) as a pathogenic factor in AKI. In this study, we investigated the therapeutic potential of a novel Chinese medicine monomer, aurantiamide (AA), which exhibits structural similarities to our previously reported GRPR antagonist, RH-1402. We compared the therapeutic efficacy of AA with RH-1402 both in vitro and in vivo using various AKI models. Our results demonstrated that, in vitro, AA attenuated injury, necroptosis, and inflammatory responses in human renal tubular epithelial cells subjected to repeated hypoxia/reoxygenation and lipopolysaccharide stimulation. In vivo, AA ameliorated renal tubular injury and inflammation in mouse models of ischemia/reperfusion and cecum ligation puncture-induced AKI, surpassing the efficacy of RH-1402. Furthermore, molecular docking and cellular thermal shift assay confirmed GRPR as a direct target of AA, which was further validated in primary cells. Notably, in GRPR-silenced HK-2 cells and GRPR systemic knockout mice, AA failed to mitigate renal inflammation and injury, underscoring the importance of GRPR in AA's mechanism of action. In conclusion, our study has demonstrated that AA serve as a novel antagonist of GRPR and a promising clinical candidate for AKI treatment.

Single-cell analysis identifies phospholysine phosphohistidine inorganic pyrophosphate phosphatase as a target in ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic gastrointestinal disorder characterized by inflammation and ulceration, representing a significant predisposition to colorectal cancer. Recent advances in single-cell RNA sequencing (scRNA-seq) technology offer a promising avenue for dissecting the complex cellular inter-actions and molecular signatures driving UC pathology. AIM: To utilize scRNA-seq technology to dissect the complex cellular interactions and molecular signatures that underlie UC pathology. METHODS: In this research, we integrated and analyzed the scRNA-seq data from UC patients. Moreover, we conducted mRNA and protein level assays as well as pathology-related staining tests on clinical patient samples. RESULTS: In this study, we identified the sustained upregulation of inflammatory response pathways during UC progression, characterized the features of damaged endo-thelial cells in colitis. Furthermore, we uncovered the downregulation of phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) has a negative correlation with signal transducer and activator of transcription 3. Significant downregulation of LHPP in UC patient tissues and plasma suggests that LHPP may serve as a potential therapeutic target for UC. This paper highlights the importance of LHPP as a potential key target in UC and unveils its potential role in inflammation regulation. CONCLUSION: The findings suggest that LHPP may serve as a potential therapeutic target for UC, emphasizing its importance as a potential key target in UC and unveiling its role in inflammation regulation.