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.

Genetic and pharmacological inhibition of GRPR protects against acute kidney injury via attenuating renal inflammation and necroptosis.

Gastrin-releasing peptide (GRP) binds to its receptor (GRP receptor [GRPR]) to regulate multiple biological processes, but the function of GRP/GRPR axis in acute kidney injury (AKI) remains unknown. In the present study, GRPR is highly expressed by tubular epithelial cells (TECs) in patients or mice with AKI, while histone deacetylase 8 may lead to the transcriptional activation of GRPR. Functionally, we uncovered that GRPR was pathogenic in AKI, as genetic deletion of GRPR was able to protect mice from cisplatin- and ischemia-induced AKI. This was further confirmed by specifically deleting the GRPR gene from TECs in GRPRFlox/Flox//KspCre mice. Mechanistically, we uncovered that GRPR was able to interact with Toll-like receptor 4 to activate STAT1 that bound the promoter of MLKL and CCL2 to induce TEC necroptosis, necroinflammation, and macrophages recruitment. This was further confirmed by overexpressing STAT1 to restore renal injury in GRPRFlox/Flox/KspCre mice. Concurrently, STAT1 induced GRP synthesis to enforce the GRP/GRPR/STAT1 positive feedback loop. Importantly, targeting GRPR by lentivirus-packaged small hairpin RNA or by treatment with a novel GRPR antagonist RH-1402 was able to inhibit cisplatin-induced AKI. In conclusion, GRPR is pathogenic in AKI and mediates AKI via the STAT1-dependent mechanism. Thus, targeting GRPR may be a novel therapeutic strategy for AKI.

Ceftriaxone improves impairments in synaptic plasticity and cognitive behavior in APP/PS1 mouse model of Alzheimer's disease by inhibiting extrasynaptic NMDAR-STEP61 signaling.

Abnormal activation of the extrasynaptic N-methyl-d-aspartate receptor (NMDAR) contributes to the pathogenesis of Alzheimer's disease (AD). Ceftriaxone (Cef) can improve cognitive impairment by upregulating glutamate transporter-1 and promoting the glutamate-glutamine cycle in an AD mouse model. This study aimed to investigate the effects of Cef on synaptic plasticity and cognitive-behavioral impairment and to unravel the associated underlying mechanisms. We used an APPswe/PS1dE9 (APP/PS1) mouse model of AD in this study. Extrasynaptic components from hippocampal tissue homogenates were isolated using density gradient centrifugation. Western blot was performed to evaluate the expressions of extrasynaptic NMDAR and its downstream elements. Intracerebroventricular injections of adeno-associated virus (AAV)-striatal enriched tyrosine phosphatase 61 (STEP61 ) and AAV-STEP61 -shRNA were used to modulate the expressions of STEP61 and extrasynaptic NMDAR. Long-term potentiation (LTP) and Morris water maze (MWM) tests were performed to evaluate the synaptic plasticity and cognitive function. The results showed that the expressions of GluN2B and GluN2BTyr1472 in the extrasynaptic fraction were upregulated in AD mice. Cef treatment effectively prevented the upregulation of GluN2B and GluN2BTyr1472 expressions. It also prevented changes in the downstream signals of extrasynaptic NMDAR, including increased expressions of m-calpain and phosphorylated p38 MAPK in AD mice. Furthermore, STEP61 upregulation enhanced, whereas STEP61 downregulation reduced the Cef-induced inhibition of the expressions of GluN2B, GluN2BTyr1472 , and p38 MAPK in the AD mice. Similarly, STEP61 modulation affected Cef-induced improvements in induction of LTP and performance in MWM tests. In conclusion, Cef improved synaptic plasticity and cognitive behavioral impairment in APP/PS1 AD mice by inhibiting the overactivation of extrasynaptic NMDAR and STEP61 cleavage due to extrasynaptic NMDAR activation.

Kallikrein-related peptidase 10 predicts prognosis and mediates tumor immunomodulation in colorectal cancer.

The incidence and mortality rates of colorectal cancer (CRC) have significantly increased in recent years. It has been shown that early diagnosis of CRC improves the five-year survival of patients compared to late diagnosis, as patients with stage I disease have a five-year survival rate as high as 90 %. Through bioinformatics analysis, we identified Kallikrein 10 (KLK10), a member of the Kallikrein family, as a reliable predictor of CRC progression, particularly in patients with early-stage CRC. Furthermore, single-cell analysis revealed that KLK10 was highly expressed in tumor and partial immune cells. Analysis of the biological functions of KLK10 using the Kyoto encyclopedia of genes and genomes and gene ontology indicated that KLK10 plays a role in the proliferation and differentiation of cancer cells, along with the maintenance of tumor function and immune regulation, explicitly by T cells and macrophages. EdU cell proliferation staining, plate clone formation assay, and cell scratch assay demonstrated that KLK10 inhibition by siRNA affected the proliferation and migration of CRC cells. Cell cycle detection by flow cytometry demonstrated that KLK10 inhibition led to cell cycle arrest in the G1 phase. In addition, the proportion of M1 and M2 macrophages in 45 tumor specimens was analyzed by immunohistochemistry, the proportion of CD4+ T cells and CD8+ T cells in plasma was identified by flow cytometry, and their correlation with KLK10 was analyzed. The effects of KLK10 on T cells and macrophages were verified in independent cell experiments. The results revealed that KLK10 also activates CD4+ T cells, mediating M2-type macrophage polarization.

Synergy effects of Methylomonas koyamae and Hyphomicrobium methylovorum under methanethiol stress.

Methanotrophs are able to metabolize volatile organic sulfur compounds (VOSCs), excrete organic carbon during CH4 oxidation, and influence microbial community structure and function of the ecosystem. In return, microbial community structure and environmental factors can affect the growth metabolism of methanotrophs. In this study, Methylomonas koyamae and Hyphomicrobium methylovorum were used for model organisms, and methanethiol (MT) was chosen for a typical VOSC to investigate the synergy effects under VOSC stress. The results showed that when Hyphomicrobium methylovorum was co-cultured with Methylomonas koyamae in the medium with CH4 used as the carbon source, the co-culture had better MT tolerance relative to Methylomonas koyamae and oxidized all CH4 within 120 h, even at the initial MT concentration of 2000 mg m-3. The optimal co-culture ratios of Methylomonas koyamae to Hyphomicrobium methylovorum were 4:1-12:1. Although MT could be converted spontaneously to dimethyl disulfide (DMDS), H2S, and CS2 in air, faster losses of MT, DMDS, H2S, and CS2 were observed in each strain mono-culture and the co-culture. Compared with Hyphomicrobium methylovorum, MT was degraded more quickly in the Methylomonas koyamae culture. During the co-culture, the CH4 oxidation process of Methylomonas koyamae could provide carbon and energy sources for the growth of Hyphomicrobium methylovorum, while Hyphomicrobium methylovorum oxidized MT to help Methylomonas koyamae detoxify. These findings are helpful to understand the synergy effects of Methylomonas koyamae and Hyphomicrobium methylovorum under MT stress and enrich the role of methanotrophs in the sulfur biogeochemical cycle. KEY POINTS: • The co-culture of Methylomonas and Hyphomicrobium has better tolerance to CH3SH. • Methylomonas can provide carbon sources for the growth of Hyphomicrobium. • The co-culture of Methylomonas and Hyphomicrobium enhances the removal of CH4 and CH3SH.

Hydrothermal treatment enhances energy recovery from pig manure digestate and improves the properties of residues.

Energy recovery from biowaste is of high significance for a sustainable society. Herein, hydrothermal treatment (HT) was applied to valorize pig manure digestate. The effects of hydrothermal operational parameters, including temperature (130-250 °C), residence time (15-90 min), and total solid (TS) concentration (10%-20%), on reducing sugar yield were investigated in this study. Among them, hydrothermal temperature was identified as the most important factor influencing reducing sugar yield, followed by the TS concentration and time. The optimal hydrothermal conditions for the pig manure digestate were 175.6 °C, 35.4 min and a TS concentration of 10% with a reduced sugar yield of 9.81 mg gTS-1. The addition of hydrolysate could enhance methane production by 21.6-50.4% from the anaerobic digestion of pig manure than that without the hydrolysate addition. After HT, the hygienic quality, including fecal coliform number and ascaris egg mortality, was improved in the residual digestate. Antibiotics such as sulfamonomethoxine, oxytetracycline, doxycycline and sulfaclodazine in the pig manure digestate were decomposed during HT and decreased environmental risk. These findings indicated that the hydrothermal process might be an effective technique to recover energy from the digestate of livestock and poultry manure and to improve the residual digestate for subsequent utilization.

CS2 increasing CH4-derived carbon emissions and active microbial diversity in lake sediments.

Lakes are important methane (CH4) sources to the atmosphere, especially eutrophic lakes with cyanobacterial blooms accompanied by volatile sulfur compound (VSC) emissions. CH4 oxidation is a key strategy to mitigate CH4 emission from lakes. In this study, we characterized the fate of CH4-derived carbon and active microbial communities in lake sediments with CS2 used as a typical VSC, based on the investigation of CH4 and VSC fluxes from Meiliang Bay in Lake Taihu. Stable isotope probing microcosm incubation showed that the efficiency of CH4-derived carbon incorporated into organic matter was 21.1% in the sediment with CS2 existence, which was lower than that without CS2 (27.3%). SO42--S was the main product of CS2 oxidation under aerobic condition, accounting for 59.3-62.7% of the input CS2-S. CS2 and CH4 coexistence led to a decrease of methanotroph and methylotroph abundances and stimulated the production of extracellular polymeric substances. CS2 and its metabolites including total sulfur, SO42- and acid volatile sulfur acted as the main drivers influencing the active microbial community structure in the sediments. Compared with α-proteobacteria methanotrophs, γ-proteobacteria methanotrophs Methylomicrobium, Methylomonas, Crenothrix and Methylosarcina were more dominant in the sediments. CH4-derived carbon mainly flowed into methylotrophs in the first stage. With CH4 consumption, more CH4-derived carbon flowed into non-methylotrophs. CS2 could prompt more CH4-derived carbon flowing into non-methanotrophs and non-methylotrophs, such as sulfur-metabolizing bacteria. These findings can help elucidate the influence of VSCs on microorganisms and provide insights to carbon fluxes from eutrophic lake systems.

Characterization of anaerobic oxidation of methane and microbial community in landfills with aeration.

Landfills are the third largest source of anthropogenic CH4 emissions. Anaerobic oxidation of methane (AOM) activity and communities of methane-oxidizing bacteria were investigated in three informal landfills in this study, namely, BJ, CH and SZ landfills, among which BJ and CH represent traditional anaerobic landfills, while the SZ landfill was subjected to aeration to accelerate waste stabilization. The AOM rates of the investigated landfilled wastes ranged from 3.66 to 23.91 nmol g-1 h-1. Among the three landfills, the AOM rate was highest in the SZ-1-Top sample, which was closest to the aeration pipe. Among the possible electron acceptors for AOM, including NO3-, NO2-, SO42- and Fe3+, the NO2--N content was the only variable that was positively correlated with the AOM rate. Compared with α-Proteobacteria methanotrophs, γ-Proteobacteria methanotrophs were more abundant in the landfilled waste, especially Methylobacter, which was detected in nearly all samples. Members of the family Methylomirabilaceae, including Candidatus Methylomirabilis, were also detected in the SZ-1 and SZ-2-Bot samples. The relative abundance of the main methanotrophs in the families Methylomonadaceae, Methylococcaceae, Rokubacteriales and Methylomirabilaceae, the genus Methylocystis and the phylum NC10 were all positive correlations with the contents of NO2--N in the landfilled waste samples. Additionally, significantly positive correlations were observed between the AOM rates and the relative abundance of the main methanotrophs except for the family Methylococcaceae. This indicated that aeration could enhance the conversion of nitrogen compounds in the landfilled waste, in which the high contents of NO2--N could stimulate the growth of methanotrophs and increase AOM rate. These findings are helpful for understanding the mechanisms of CH4 oxidation in landfills and for taking effective measures to mitigate CH4 emissions from landfills.

Design, synthesis, and biological evaluation of novel 3-(thiophen-2-ylthio)pyridine derivatives as potential multitarget anticancer agents.

A series of novel 3-(thiophen-2-ylthio)pyridine derivatives as insulin-like growth factor 1 receptor (IGF-1R) inhibitors was designed and synthesized. IGF-1R kinase inhibitory activities and cytotoxicities against HepG2 and WSU-DLCL2 cell lines were tested. For all of these compounds, potent cancer cell proliferation inhibitory activities were observed, but not through the inhibition of IGR-1R. Selected compounds were further screened against various kinases. Typical compound 22 (50% inhibitory concentration [IC50 ] values, HepG2: 2.98 ± 1.11 µM and WSU-DLCL2: 4.34 ± 0.84 µM) exhibited good inhibitory activities against fibroblast growth factor receptor-2 (FGFR2), FGFR3, epidermal growth factor receptor, Janus kinase, and RON (receptor originated from Nantes), with IC50 values ranging from 2.14 to 12.20 µM. Additionally, the cell-cycle analysis showed that compound 22 could arrest HepG2 cells in the G1/G0 phase. Taken together, all the experiments confirmed that the compounds in this series were multitarget anticancer agents worth further optimizing.

Behavioral and circuit basis of sucrose rejection by Drosophila females in a simple decision-making task.

Drosophila melanogaster egg-laying site selection offers a genetic model to study a simple form of value-based decision. We have previously shown that Drosophila females consistently reject a sucrose-containing substrate and choose a plain (sucrose-free) substrate for egg laying in our sucrose versus plain decision assay. However, either substrate is accepted when it is the sole option. Here we describe the neural mechanism that underlies females' sucrose rejection in our sucrose versus plain assay. First, we demonstrate that females explored the sucrose substrate frequently before most egg-laying events, suggesting that they actively suppress laying eggs on the sucrose substrate as opposed to avoiding visits to it. Second, we show that activating a specific subset of DA neurons triggered a preference for laying eggs on the sucrose substrate over the plain one, suggesting that activating these DA neurons can increase the value of the sucrose substrate for egg laying. Third, we demonstrate that neither ablating nor inhibiting the mushroom body (MB), a known Drosophila learning and decision center, affected females' egg-laying preferences in our sucrose versus plain assay, suggesting that MB does not mediate this specific decision-making task. We propose that the value of a sucrose substrate- as an egg-laying option-can be adjusted by the activities of a specific DA circuit. Once the sucrose substrate is determined to be the lesser valued option, females execute their decision to reject this inferior substrate not by stopping their visits to it, but by actively suppressing their egg-laying motor program during their visits.

Methane-derived carbon flow through microbial communities in arctic lake sediments.

Aerobic methane (CH4 ) oxidation mitigates CH4 release and is a significant pathway for carbon and energy flow into aquatic food webs. Arctic lakes are responsible for an increasing proportion of global CH4 emissions, but CH4 assimilation into the aquatic food web in arctic lakes is poorly understood. Using stable isotope probing (SIP) based on phospholipid fatty acids (PLFA-SIP) and DNA (DNA-SIP), we tracked carbon flow quantitatively from CH4 into sediment microorganisms from an arctic lake with an active CH4 seepage. When 0.025 mmol CH4 g(-1) wet sediment was oxidized, approximately 15.8-32.8% of the CH4 -derived carbon had been incorporated into microorganisms. This CH4 -derived carbon equated to up to 5.7% of total primary production estimates for Alaskan arctic lakes. Type I methanotrophs, including Methylomonas, Methylobacter and unclassified Methylococcaceae, were most active at CH4 oxidation in this arctic lake. With increasing distance from the active CH4 seepage, a greater diversity of bacteria incorporated CH4 -derived carbon. Actinomycetes were the most quantitatively important microorganisms involved in secondary feeding on CH4 -derived carbon. These results showed that CH4 flows through methanotrophs into the broader microbial community and that type I methanotrophs, methylotrophs and actinomycetes are important organisms involved in using CH4 -derived carbon in arctic freshwater ecosystems.

Leptin Is Oversecreted by Respiratory Syncytial Virus-Infected Bronchial Epithelial Cells and Regulates Th2 and Th17 Cell Differentiation.

BACKGROUND: Infection of human bronchial epithelial cells (hBECs) with respiratory syncytial virus (RSV) has been shown to induce a Th lymphocyte subset drift, e.g. enhanced differentiation of Th2 and Th17 subsets, which is a classic characteristic of asthma. However, the molecules responsible for the drift in Th subsets remain unknown. This study aims to determine the expression of leptin in RSV-infected hBECs, and its role in Th2 and Th17 cell differentiation and extracellular regulated kinase (ERK) 1/2 phosphorylation. METHODS: Cultured hBECs were infected with RSV. mRNA expression of the LEP gene in cells was measured by real-time PCR while LEP protein secretion in culture medium was measured by ELISA. Th differentiation was investigated in cultured human peripheral blood mononuclear cells following stimulation with recombinant human leptin. Th2 and Th17 subsets were examined by flow cytometry. Phosphorylation of the ERK1/2 protein in lymphocytes was detected by Western blot and immunofluorescence. RESULTS: LEP mRNA expression was significantly upregulated in RSV-infected hBECs while the leptin protein level in the supernatants of RSV-infected hBECs was significantly increased. Stimulation of lymphocytes with leptin increased the differentiation of the Th17 subset and ERK1/2 phosphorylation, but suppressed Th2 subset differentiation. CONCLUSION: Leptin was oversecreted by RSV-infected hBECs, which promoted Th17 subset differentiation but suppressed Th2 subset differentiation possibly via regulating ERK1/2 phosphorylation.

Microbial community and function of enrichment cultures with methane and toluene.

The interaction effect of co-existence of toluene and CH4 on community and activity of methanotrophs and toluene-degrading bacteria was characterized in three consortia enriched with CH4 and toluene (MT), toluene (T), and CH4 (M), respectively, in this study. The CH4 oxidation activity in the enrichment culture of MT was significantly lower than that of M at the end of the experiment (P = 0.001). The toluene degradation rate could be enhanced by continuous addition of CH4 and toluene in the initial days, but it was inhibited in the later days. Phylogenetic analysis of 16S rRNA genes showed that Proteobacteria and Bacteroidetes were dominant in the three enriched consortia, but the community of methanotrophs and toluene-degrading bacteria was significantly affected by the co-existence of CH4 and toluene. Both Methylosinus (91.8 %) and Methylocystis (8.2 %) were detected in the enrichment culture of MT, while only Methylocystis species were detected in M. The toluene-degrading bacteria including Burkholderia, Flavobacteria, Microbacterium, and Azoarcus were all detected in the enrichment culture of T. However, only Azoarcus was found in the enrichment culture of MT. Significantly higher contents of extracellular polymeric substances polysaccharose and protein in the enrichment culture of MT than that of T and M suggested that a higher environmental stress occurred in the enrichment culture of MT.

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.

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.

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.

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.

Estimation of sulfur fate and contribution to VSC emissions from lakes during algae decay.

Algae decay is an important process influencing environmental variables and emissions of volatile sulfur compounds (VSCs) in eutrophic lakes. However, effects of algae decay on VSC emissions from eutrophic lakes as well as fate of algae-derived sulfur remain poorly understood. In this study, simulated algae-sediment systems were used to explore the flow and distribution of sulfur during algae decay. VSCs including hydrogen sulfide (H2S), methanethiol (CH3SH), carbon disulfide (CS2) and dimethyl sulfide ((CH3)2S) were detected during algae decay, which increased with algae biomass and eutrophic levels in lakes. During algae decay, the highest H2S, CH3SH and (CH3)2S emission rates of 10.45, 21.82 and 43.26 µg d-1 occurred in the first 1-2 days, respectively, while the highest CS2 emission rates were observed between days 8 and 11. The maximum emissions of H2S and CS2 from algae decay were estimated at 0.51 and 0.35 mg m-2 d-1 in Lake Taihu, accounting for 1.57% and 0.69% of the total H2S and CS2 emissions of in situ, respectively. Algae decay could significantly increase the contents of total sulfur and total carbon in sediments by 2.90%-21.11% and 4.23%-45.05%, respectively. The VSC emissions during algae decay could be predicted using the multiple regression models with the contents of total carbon, total nitrogen and sulfur-containing compounds in sediments. Partial least squares path modelling demonstrated that algae decay had a low direct effect on VSC emissions with a strength of 0.06, while it had a significant influence on environmental variables with a strength of 0.63, which could affect VSC emissions with a strength of 0.85, indicating VSC emissions from eutrophic lakes were affected by the environmental variables rather than the direct influence of algae decay. These findings illustrated the mechanisms of VSC emissions during algae decay and provided insights into VSC control and mitigation for eutrophic lakes.