Bioreduction of chromate in a syngas-based membrane biofilm reactor.

This study leveraged synthesis gas (syngas), a renewable resource attainable through the gasification of biowaste, to achieve efficient chromate removal from water. To enhance syngas transfer efficiency, a membrane biofilm reactor (MBfR) was employed. Long-term reactor operation showed a stable and high-level chromate removal efficiency > 95%, yielding harmless Cr(III) precipitates, as visualised by scanning electron microscopy and energy dispersive X-ray analysis. Corresponding to the short hydraulic retention time of 0.25 days, a high chromate removal rate of 80 µmol/L/d was attained. In addition to chromate reduction, in situ production of volatile fatty acids (VFAs) by gas fermentation was observed. Three sets of in situ batch tests and two groups of ex situ batch tests jointly unravelled the mechanisms, showing that biological chromate reduction was primarily driven by VFAs produced from in situ syngas fermentation, whereas hydrogen originally present in the syngas played a minor role. 16 S rRNA gene amplicon sequencing has confirmed the enrichment of syngas-fermenting bacteria (such as Sporomusa), who performed in situ gas fermentation leading to the synthesis of VFAs, and organics-utilising bacteria (such as Aquitalea), who utilised VFAs to drive chromate reduction. These findings, combined with batch assays, elucidate the pathways orchestrating synergistic interactions between fermentative microbial cohorts and chromate-reducing microorganisms. The findings facilitate the development of cost-effective strategies for groundwater and drinking water remediation and present an alternative application scenario for syngas.

Anaerobic oxidation of ammonium and short-chain gaseous alkanes coupled to nitrate reduction by a bacterial consortium.

The bacterial species 'Candidatus Alkanivorans nitratireducens' was recently demonstrated to mediate nitrate-dependent anaerobic oxidation of short-chain gaseous alkanes (SCGAs). In previous bioreactor enrichment studies1,2, the species appeared to reduce nitrate in two phases, switching from denitrification to dissimilatory nitrate reduction to ammonium (DNRA) in response to nitrite accumulation. The regulation of this switch or the nature of potential syntrophic partnerships with other microorganisms remains unclear. Here, we describe anaerobic multispecies cultures of bacteria which couple the oxidation of propane and butane to nitrate reduction and the oxidation of ammonium (anammox). Batch tests with 15N-isotope labelling and multi-omic analyses collectively supported a syntrophic partnership between 'Ca. A. nitratireducens' and anammox bacteria, with the former species mediating nitrate-driven oxidation of SCGAs, supplying the latter with nitrite for the oxidation of ammonium. The elimination of nitrite accumulation by the anammox substantially increased SCGA and nitrate consumption rates, whereas suppressing DNRA. Removing ammonium supply led to its eventual production, the accumulation of nitrite, and the upregulation of DNRA gene expression for the abundant 'Ca. A. nitratireducens'. Increasing the supply of SCGA had a similar effect in promoting DNRA. Our results suggest that 'Ca. A. nitratireducens' switches to DNRA to alleviate oxidative stress caused by nitrite accumulation, giving further insight into adaptability and ecology of this microorganism. Our findings also have important implications for the understanding of the fate of nitrogen and SCGAs in anaerobic environments.

Coupling Partial Nitritation, Anammox and n-DAMO in a membrane aerated biofilm reactor for simultaneous dissolved methane and nitrogen removal.

Anaerobic technologies with downstream autotrophic nitrogen removal have been proposed to enhance bioenergy recovery and transform a wastewater treatment plant from an energy consumer to an energy exporter. However, approximately 20-50 % of the produced methane is dissolved in the anaerobically treated effluent and is easily stripped into the atmosphere in the downstream aerobic process, contributing to the release of greenhouse gas emissions. This study aims to develop a solution to beneficially utilize dissolved methane to support high-level nitrogen removal from anaerobically treated mainstream wastewater. A novel technology, integrating Partial Nitritation, Anammox and Methane-dependent nitrite/nitrate reduction (i.e. PNAM) was demonstrated in a membrane-aerated biofilm reactor (MABR). With the feeding of ∼50 mg NH4+-N/L and ∼20 mg/L dissolved methane at a hydraulic retention time of 15 h, around 90 % of nitrogen and ∼100 % of dissolved methane can be removed together in the MABR. Microbial community characterization revealed that ammonia-oxidizing bacteria (AOB), nitrite-oxidizing bacteria (NOB), anammox bacteria, nitrite/nitrate-dependent anaerobic methane oxidation microorganisms (n-DAMO bacteria and archaea) and aerobic methanotrophs co-existed in the established biofilm. Batch tests confirmed the active microbial pathways and showed that AOB, anammox bacteria and n-DAMO microbes were jointly responsible for the nitrogen removal, and dissolved methane was mainly removed by the n-DAMO process, with aerobic methane oxidation making a minor contribution. In addition, the established system was robust against dynamic changes in influent composition. The study provides a promising technology for the simultaneous removal of dissolved methane and nitrogen from domestic wastewater, which can support the transformation of wastewater treatment from an energy- and carbon-intensive process, to one that is energy- and carbon-neutral.

Biological bromate reduction coupled with in situ gas fermentation in H2/CO2-based membrane biofilm reactor.

Bromate, a carcinogenic contaminant generated in water disinfection, presents a pressing environmental concern. While biological bromate reduction is an effective remediation approach, its implementation often necessitates the addition of organics, incurring high operational costs. This study demonstrated the efficient biological bromate reduction using H2/CO2 mixture as the feedstock. A membrane biofilm reactor (MBfR) was used for the efficient delivery of gases. Long-term reactor operation showed a high-level bromate removal efficiency of above 95 %, yielding harmless bromide as the final product. Corresponding to the short hydraulic retention time of 0.25 d, a high bromate removal rate of 4 mg Br/L/d was achieved. During the long-term operation, in situ production of volatile fatty acids (VFAs) by gas fermentation was observed, which can be regulated by controlling the gas flow. Three sets of in situ batch tests and two groups of ex situ batch tests jointly unravelled the mechanisms underpinning the efficient bromate removal, showing that the microbial bromate reduction was primarily driven by the VFAs produced from in situ gas fermentation. Microbial community analysis showed an increased abundance of Bacteroidota group from 4.0 % to 18.5 %, which is capable of performing syngas fermentation, and the presence of heterotrophic denitrifiers (e.g., Thauera and Brachymonas), which are known to perform bromate reduction. Together these results for the first time demonstrated the feasibility of using H2/CO2 mixture for bromate removal coupled with in situ VFAs production. The findings can facilitate the development of cost-effective strategies for groundwater and drinking water remediation.

Revisiting methane-dependent denitrification.

Methane-dependent denitrification links the global nitrogen and methane cycles. Since its initial discovery in 2006, this process has been understood to involve a division of labor between an archaeal group and a bacterial group, which sequentially perform nitrate and nitrite reduction, respectively. Yao et al. have now revised this paradigm by identifying a Methylomirabilis bacterium capable of performing methane-dependent complete denitrification on its own.

Discovery of anticancer function of Febrifugine: Inhibition of cell proliferation, induction of apoptosis and suppression steroid synthesis in bladder cancer cells.

Bladder cancer is a prevalent malignancy affecting the urinary system, which presents a significant global health concern. Although there are many treatments for bladder cancer, identifying more effective drugs and methods remains an urgent problem. As a pivotal component of contemporary medical practice, traditional Chinese medicine (TCM) assumes a crucial role in the realm of anti-tumor therapy, especially with the identification of active ingredients and successful exploration of pharmacological effects. Febrifugine, identified as a quinazoline-type alkaloid compound extracted from the Cytidiaceae family plant Huangchangshan, exhibits heightened sensitivity to bladder cancer cells in comparison to control cells (non-cancer cells) group. The proliferation growth of bladder cancer cells T24 and SW780 was effectively inhibited by Febrifugine, and the IC50 was 0.02 and 0.018 µM respectively. Febrifugine inhibits cell proliferation by suppressing DNA synthesis and induces cell death by reducing steroidogenesis and promoting apoptosis. Combined with transcriptome analysis, Febrifugine was found to downregulate low density lipoprotein receptor-associated protein, lanosterol synthase, cholesterol biosynthesis second rate-limiting enzyme, 7-dehydrocholesterol reductase, flavin adenine dinucleotide dependent oxidoreductase and other factors to inhibit the production of intracellular steroids in bladder cancer T24 cells. The results of animal experiments showed that Febrifugine could inhibit tumor growth. In summary, the effect of Febrifugine on bladder cancer is mainly through reducing steroid production and apoptosis. Therefore, this study contributes to the elucidation of Febrifugine's potential as an inhibitor of bladder cancer and establishes a solid foundation for the future development of novel therapeutic agents targeting bladder cancer.

Occurrence, transmission and risks assessment of pathogens in aquatic environments accessible to humans.

Pathogens are ubiquitously detected in various natural and engineered water systems, posing potential threats to public health. However, it remains unclear which human-accessible waters are hotspots for pathogens, how pathogens transmit to these waters, and what level of health risk associated with pathogens in these environments. This review collaboratively focuses and summarizes the contamination levels of pathogens on the 5 water systems accessible to humans (natural water, drinking water, recreational water, wastewater, and reclaimed water). Then, we showcase the pathways, influencing factors and simulation models of pathogens transmission and survival. Further, we compare the health risk levels of various pathogens through Quantitative Microbial Risk Assessment (QMRA), and assess the limitations of water-associated QMRA application. Pathogen levels in wastewater are consistently higher than in other water systems, with no significant variation for Cryptosporidium spp. among five water systems. Hydraulic conditions primarily govern the transmission of pathogens into human-accessible waters, while environmental factors such as temperature impact pathogens survival. The median and mean values of computed public health risk levels posed by pathogens consistently surpass safety thresholds, particularly in the context of recreational waters. Despite the highest pathogens levels found in wastewater, the calculated health risk is significantly lower than in other water systems. Except pathogens concentration, variables like the exposure mode, extent, and frequency are also crucial factors influencing the public health risk in water systems. This review shares valuable insights to the more accurate assessment and comprehensive management of public health risk in human-accessible water environments.

Effect of Low-Temperature Plasma-Modified Carbon Fibers on Impact Load Damage of Low-Density Oil-Well Cement.

After large-scale exploitation of conventional oil and gas resources, most remaining resources are in highly depleted zones, where the fracture pressure of the formations is greatly reduced. Low-density oil-well cement prevents wellbore and formation fractures by reducing annular liquid column pressure and is one of the most commonly used cements in the oil and gas industry. However, cement sheaths made of low-density oil-well cement can be easily damaged due to the impact load generated during the well completion process. Incorporating carbon fibers into the cement matrix can effectively enhance the performance of cement sheaths. To ensure that carbon fibers can be closely combined with the cement matrix, low-temperature plasma modification technology was used in this study to pretreat the fibers. The mechanical properties of low-density oil-well cement incorporated with unmodified or modified carbon fibers were studied in detail under an impact load. The results of X-ray photoelectron spectroscopy revealed that the content of hydrophilic groups on the surface increased from 18.3 to 60.3% after the plasma treatment. The impact test results showed that the peak strengths of the cements cured at 60 °C for 14 days with 0.3% unmodified and modified carbon fibers could reach 37.01 ± 1.7 and 62.27 ± 1.7 MPa, respectively, under the impact load, i.e., an increase of 68.25% after the carbon fibers were treated with low-temperature plasma. Similarly, the absorbed energy increased from 15.59 to 44.31 J, and the energy absorption rate increased from 25.98 to 73.85%. Low-temperature plasma modification provided hydrophilic functional groups on the surface, significantly improving the interfacial bonding between the carbon fibers and cement matrix. The strengthened interaction was beneficial to extending the bearing time under the impact load and demonstrated a positive influence on the mechanical properties related to the impact resistance.

Zebrafish Mbd5 binds to RNA m5C and regulates histone deubiquitylation and gene expression in development metabolism and behavior.

Complex biological processes are regulated by both genetic and epigenetic programs. One class of epigenetic modifications is methylation. Evolutionarily conserved methyl-CpG-binding domain (MBD)-containing proteins are known as readers of DNA methylation. MBD5 is linked to multiple human diseases but its mechanism of action remains unclear. Here we report that the zebrafish Mbd5 does not bind to methylated DNA; but rather, it directly binds to 5-methylcytosine (m5C)-modified mRNAs and regulates embryonic development, erythrocyte differentiation, iron metabolism, and behavior. We further show that Mbd5 facilitates removal of the monoubiquitin mark at histone H2A-K119 through an interaction with the Polycomb repressive deubiquitinase (PR-DUB) complex in vivo. The direct target genes of Mbd5 are enriched with both RNA m5C and H2A-K119 ubiquitylation signals. Together, we propose that zebrafish MBD5 is an RNA m5C reader that potentially links RNA methylation to histone modification and in turn transcription regulation in vivo.

Inter-plasmid transfer of antibiotic resistance genes accelerates antibiotic resistance in bacterial pathogens.

Antimicrobial resistance is a major threat for public health. Plasmids play a critical role in the spread of antimicrobial resistance via horizontal gene transfer between bacterial species. However, it remains unclear how plasmids originally recruit and assemble various antibiotic resistance genes (ARGs). Here, we track ARG recruitment and assembly in clinically relevant plasmids by combining a systematic analysis of 2420 complete plasmid genomes and experimental validation. Results showed that ARG transfer across plasmids is prevalent, and 87% ARGs were observed to potentially transfer among various plasmids among 8229 plasmid-borne ARGs. Interestingly, recruitment and assembly of ARGs occur mostly among compatible plasmids within the same bacterial cell, with over 88% of ARG transfers occurring between compatible plasmids. Integron and insertion sequences drive the ongoing ARG acquisition by plasmids, especially in which IS26 facilitates 63.1% of ARG transfer events among plasmids. In vitro experiment validated the important role of IS26 involved in transferring gentamicin resistance gene aacC1 between compatible plasmids. Network analysis showed four beta-lactam genes (blaTEM-1, blaNDM-4, blaKPC-2, and blaSHV-1) shuffling among 1029 plasmids and 45 clinical pathogens, suggesting that clinically alarming ARGs transferred accelerate the propagation of antibiotic resistance in clinical pathogens. ARGs in plasmids are also able to transmit across clinical and environmental boundaries, in terms of the high-sequence similarities of plasmid-borne ARGs between clinical and environmental plasmids. This study demonstrated that inter-plasmid ARG transfer is a universal mechanism for plasmid to recruit various ARGs, thus advancing our understanding of the emergence of multidrug-resistant plasmids.

Nitrate-driven anaerobic oxidation of ethane and butane by bacteria.

The short-chain gaseous alkanes (ethane, propane, and butane; SCGAs) are important components of natural gas, yet their fate in environmental systems is poorly understood. Microbially mediated anaerobic oxidation of SCGAs coupled to nitrate reduction has been demonstrated for propane, but is yet to be shown for ethane or butane-despite being energetically feasible. Here we report two independent bacterial enrichments performing anaerobic ethane and butane oxidation, respectively, coupled to nitrate reduction to dinitrogen gas and ammonium. Isotopic 13C- and 15N-labelling experiments, mass and electron balance tests, and metabolite and meta-omics analyses collectively reveal that the recently described propane-oxidizing "Candidatus Alkanivorans nitratireducens" was also responsible for nitrate-dependent anaerobic oxidation of the SCGAs in both these enrichments. The complete genome of this species encodes alkylsuccinate synthase genes for the activation of ethane/butane via fumarate addition. Further substrate range tests confirm that "Ca. A. nitratireducens" is metabolically versatile, being able to degrade ethane, propane, and butane under anoxic conditions. Moreover, our study proves nitrate as an additional electron sink for ethane and butane in anaerobic environments, and for the first time demonstrates the use of the fumarate addition pathway in anaerobic ethane oxidation. These findings contribute to our understanding of microbial metabolism of SCGAs in anaerobic environments.

Correlation of microbial community structure and volatile flavor compounds during corn yellow wine fermentation.

High-throughput sequencing was used to define microbial community structure and GC-MS to identify volatile flavor substances during fermentation of corn yellow wine, and results were analyzed by multivariate statistical analysis. Seventeen bacterial phyla, 239 bacterial genera, 4 fungal phyla, and 18 fungal genera were found and changes in community structure occurred during fermentation. Twenty-four volatile flavor substances, including 14 esters and 5 alcohols, were detected and changes during fermentation recorded. Sixteen microbial genera correlated with volatile flavor substances and Weissella, Lactobacillus, Pseudomonas, Rhodotorul, and Kwoniella had significant correlation with ethyl esters and higher alcohols. Micro-organisms thus influence flavor development during corn yellow wine fermentation.

Long-Term Field Application of a Plant Growth-Promoting Rhizobacterial Consortium Suppressed Root-Knot Disease by Shaping the Rhizosphere Microbiota.

Root-knot nematodes (Meloidogyne spp.) are one of the most economically important plant parasitic nematodes, infecting almost all cultivated plants and resulting in severe yield losses every year. Plant growth-promoting rhizobacteria (PGPR) have been extensively used to prevent and control root-knot diseases and increase yield. In this study, the effect of a consortium of three PGPR strains (Bacillus cereus AR156, B. subtilis SM21, and Serratia sp. XY21; hereafter "BBS") on root-knot disease of cucumber was evaluated. The application of BBS significantly reduced the severity of root-knot disease by 56 to 72%, increased yield by 36 to 55%, and improved fruit quality by 14 to 90% and soil properties by 1 to 90% relative to the control in the cucumber fields of the Nanjing suburb, Jiangsu Province, from 2015 to 2018. BBS altered the rhizosphere bacterial community. Compared with the control group, it significantly (false discovery rate, P < 0.05) increased the abundance of 14 bacterial genera that were negatively correlated with disease severity. Additionally, the redundancy analysis suggested that BBS-treated rhizosphere soil samples were dominated by disease-suppressive bacteria, including the genera Iamia, Kutzneria, Salinibacterium, Mycobacterium, Kribbella, Pseudonocardia, Sporichthya, Sphaerisporangium, Actinomadura, Flavisolibacter, Phenylobacterium, Bosea, Hyphomicrobium, Agrobacterium, Sphingomonas, and Nannocystis, which were positively related to total organic carbon, total nitrogen, total organic matter, dissolved organic carbon, [Formula: see text]-N, and available phosphorus contents. This suggests that BBS suppresses root-knot nematodes and improves the soil chemical properties of cucumber by altering the rhizosphere microbial community.

Methane Oxidation Coupled to Selenate Reduction in a Membrane Bioreactor under Oxygen-Limiting Conditions.

Microbial methane oxidation coupled to a selenate reduction process has been proposed as a promising solution to treat contaminated water, yet the underlying microbial mechanisms are still unclear. In this study, a novel methane-based membrane bioreactor system integrating hollow fiber membranes for efficient gas delivery and ultrafiltration membranes for biomass retention was established to successfully enrich abundant suspended cultures able to perform methane-dependent selenate reduction under oxygen-limiting conditions. The microbial metabolic mechanisms were then systematically investigated through a combination of short-term batch tests, DNA-based stable isotope probing (SIP) microcosm incubation, and high-throughput sequencing analyses of 16S rRNA gene and functional genes (pmoA and narG). We confirmed that the methane-supported selenate reduction process was accomplished by a microbial consortia consisting of type-II aerobic methanotrophs and several heterotrophic selenate reducers. The mass balance and validation tests on possible intermediates suggested that methane was partially oxidized into acetate under oxygen-limiting conditions, which was consumed as a carbon source for selenate-reducing bacteria. High-throughput 16S rRNA gene sequencing, DNA-SIP incubation with 13CH4, and subsequent functional gene (pmoA and narG) sequencing results collectively proved that Methylocystis actively executed partial methane oxidation and Acidovorax and Denitratisoma were dominant selenate-reducing bacteria, thus forming a syntrophic partnership to drive selenate reduction. The findings not only advance our understanding of methane oxidation coupled to selenate reduction under oxygen-limiting conditions but also offer useful information on developing methane-based biotechnology for bioremediation of selenate-contaminated water.

Extended water stagnation in buildings during the COVID-19 pandemic increases the risks posed by opportunistic pathogens.

The regrowth and subsequent exposure of opportunistic pathogens (OPs) whilst reopening buildings that have been locked down due to the stay-at-home restrictions to limit the spread of COVID-19, is a public health concern. To better understand such microbiological risks due to lowered occupancy and water demand in buildings, first and post-flush water samples (n = 48) were sampled from 24 drinking water outlets from eight university buildings in two campuses (urban and rural), with various end-user occupancies. Both campuses were served with chlorinated water originating from a single drinking water distribution system in South-East Queensland, situated 14 km apart, where the rural campus had lower chlorine residuals. Culture-dependent and culture-independent methods (such as flow cytometry, qPCR and 16S rRNA gene amplicon sequencing) were used concurrently to comprehensively characterise the OPs of interest (Legionella spp., Pseudomonas aeruginosa, and nontuberculous mycobacteria (NTM)) and the premise plumbing microbiome. Results showed that buildings with extended levels of stagnation had higher and diverse levels of microbial growth, as observed in taxonomic structure and composition of the microbial communities. NTM were ubiquitous in all the outlets sampled, regardless of campus or end-user occupancy of the buildings. qPCR and culture demonstrated prevalent and higher concentrations of NTM in buildings (averaging 3.25 log10[estimated genomic copies/mL]) with extended stagnation in the urban campus. Furthermore, flushing the outlets for 30 minutes restored residual and total chlorine, and subsequently decreased the levels of Legionella by a reduction of 1 log. However, this approach was insufficient to restore total and residual chlorine levels for the outlets in the rural campus, where both Legionella and NTM levels detected by qPCR remained unchanged, regardless of building occupancy. Our findings highlight that regular monitoring of operational parameters such as residual chlorine levels, and the implementation of water risk management plans are important for non-healthcare public buildings, as the levels of OPs in these environments are typically not assessed.

MOPDDI: Predicting Drug-Drug Interaction Events Based on Multimodal Mutual Orthogonal Projection and Intermodal Consistency Loss.

Predicting accurately the mechanisms of drug-drug interaction (DDI) events is crucial in drug research and development. Existing methods used to predict these events are primarily based on deep learning and have achieved satisfactory results. However, they rarely consider the presence of redundant co-information between the multimodal data of a drug and the need for consistency in the predicted features of each drug modality. Herein, we propose a new method for drug interaction event prediction based on multimodal mutual orthogonal projection and intermodal consistency loss. Our method obtains the features of each modality through a multimodal mutual orthogonal projection module, which eliminates redundant common information with other modalities. In addition, we use the consistency loss between modalities and make the predicted features of each modality more similar. In comparative experiments, our proposed method achieves a prediction accuracy of 0.9500, and an area under the precision-recall (AUPR) curve is 0.9833 for known DDIs. This method outperforms existing methods. The results show that the proposed method is capable of accurately predicting DDIs. The source code is available at https://github.com/xiaqixiaqi/MOPDDI.

Tumor microenvironment heterogeneity in bladder cancer identifies biologically distinct subtypes predicting prognosis and anti-PD-L1 responses.

Bladder cancer (BCa) is heterogeneous in the tumour microenvironment (TME). However, the role of the TME in BCa in modulating the response to immunotherapy has not been fully explored. We therefore analysed fractions of immune cells using CIBERSORTx and clustered BCa into subtypes. We also analyzed weighted correlation networks to generate immunotherapy-related hub genes that we used to construct a prediction model using multivariate Cox and LASSO regression analyses. We found that BCa comprised three subtypes (C1‒C3). The prognosis of the patients was the most favourable and the response rate to anti-programmed death ligand 1 (PD-L1) was the highest in C1 among the three subtypes. Immune cells, including CD8+, CD4+ memory activated, and follicular helper T cells, activated NK cells, and M1 macrophages infiltrated the C1 subtype. The C2 subtype was enriched in M0 macrophages and activated mast cells, and the C3 subtype was enriched in B and resting immune cells. Mechanistically, the enhanced immunogenicity of subtypes C1 and C2 correlated positively with a higher response rate, whereas the dysregulated ECM-related pathways in the C2 subtype and glycolytic and fatty acid metabolic pathways in the C3 subtype impaired the responses of patients to anti-PD-L1 therapy. We also constructed a TME-related signature based on 18 genes that performed well in terms of overall survival. In conclusion, we determined prognoses and anti-PD-L1 responses by analysing TME heterogeneity in BCa.

Prevalence and transmission risk of colistin and multidrug resistance in long-distance coastal aquaculture.

Due to the wide use of antibiotics, intensive aquaculture farms have been recognized as a significant reservoir of antibiotic resistomes. Although the prevalence of colistin resistance genes and multidrug-resistant bacteria (MDRB) has been documented, empirical evidence for the transmission of colistin and multidrug resistance between bacterial communities in aquaculture farms through horizontal gene transfer (HGT) is lacking. Here, we report the prevalence and transmission risk of colistin and multidrug resistance in 27 aquaculture water samples from 9 aquaculture zones from over 5000 km of subtropical coastlines in southern China. The colistin resistance gene mcr-1, mobile genetic element (MGE) intl1 and 13 typical antibiotic resistance genes (ARGs) were prevalent in all the aquaculture water samples. Most types of antibiotic (especially colistin) resistance are transmissible in bacterial communities based on evidence from laboratory conjugation and transformation experiments. Diverse MDRB were detected in most of the aquaculture water samples, and a strain with high-level colistin resistance, named Ralstonia pickettii MCR, was isolated. The risk of horizontal transfer of the colistin resistance of R. pickettii MCR through conjugation and transformation was low, but the colistin resistance could be steadily transmitted to offspring through vertical transfer. The findings have important implications for the future regulation of antibiotic use in aquaculture farms globally to address the growing threat posed by antibiotic resistance to human health.

Proteomics, Transcriptomics, and Phosphoproteomics Reveal the Mechanism of Talaroconvolutin-A Suppressing Bladder Cancer via Blocking Cell Cycle and Triggering Ferroptosis.

Talaroconvolutin-A (TalaA) is a compound from the endophytic fungus T. convolutispora of the Chinese herbal medicine Panax notoginseng. Whether TalaA exerts anticancer activity in bladder cancer remains unknown. Using CCK8 assay, EdU staining, crystal violet staining, flow cytometry, living/dead cell staining, and Western blotting, we studied the anticancer activity of TalaA in vitro. Moreover, we performed xenograft tumor implantation. The antitumor effects were evaluated through H&E and immunohistochemistry staining. Proteomics was conducted to detect changes in the protein profile; transcriptomics was performed to detect changes in mRNA abundance; phosphoproteomics was used to detect changes in protein phosphorylation. TalaA inhibited tumor cell proliferation, DNA replication, and colony formation in a dose-dependent manner in bladder cancer cells. The IC50 values of TalaA on SW780 and UM-UC-3 cells were 5.7 and 8.2 µM, respectively. TalaA (6.0 mg/kg) significantly repressed the growth of xenografted tumors and did not affect the body weight nor cause obvious hepatorenal toxicity. TalaA arrested the cell cycle by downregulating cyclinA2, cyclinB1, and AURKB and upregulating p21/CIP. TalaA also elevated intracellular reactive oxygen species and upregulated transferrin and heme oxygenase 1 to induce ferroptosis. Moreover, TalaA was able to bind to MAPKs (MAPK1, MAPK8, and MAPK14) to inhibit the phosphorylation of ∗SP∗ motif of transcription regulators. This study revealed that TalaA inhibited bladder cancer by arresting cell cycle to suppress proliferation and triggering ferroptosis to cause cell death. Conclusively, TalaA would be a potential candidate for treating bladder cancer by targeting MAPKs, suppressing the cell cycle, and inducing ferroptosis.

Challenges of suppressing nitrite-oxidizing bacteria in membrane aerated biofilm reactors by low dissolved oxygen control.

Membrane aerated biofilm reactor (MABR) and shortcut nitrogen removal are two types of solutions to reduce energy consumption in wastewater treatment, with the former improving the aeration efficiency and the latter reducing the oxygen demand. However, integrating these two solutions, i.e., achieving shortcut nitrogen removal in MABR, is challenging due to the difficulty in suppressing nitrite-oxidizing bacteria (NOB). In this study, four MABRs were established to demonstrate the feasibility of initiating, maintaining, and restoring NOB suppression using low dissolved oxygen (DO) control, in the presence and absence of anammox bacteria, respectively. Long-term results revealed that the strict low DO (< 0.1 mg/L) in MABR could initiate and maintain stable NOB suppression for more than five months with nitrite accumulation ratio above 90 %, but it was unable to re-suppress NOB once they prevailed. Moreover, the presence of anammox bacteria increased the threshold of DO level to maintain NOB suppression in MABRs, but it was still incapable to restore the deteriorated NOB suppression in conjunction with low DO control. Mathematical modelling confirmed the experimental results and further explored the differences of NOB suppression in conventional biofilms and MABR biofilms. Simulation results showed that it is more challenging to maintain stable NOB suppression in MABRs compared to conventional biofilms, regardless of biofilm thickness or influent nitrogen concentration. Kinetic mechanisms for NOB suppression in different types of biofilms were proposed, suggesting that it is difficult to wash out NOB developed in the innermost layer of MABR biofilms because of the high oxygen level and low sludge wasting rate. In summary, this study systematically demonstrated the challenges of NOB suppression in MABRs through both experiments and mathematical modelling. These findings provide valuable insights into the applications of MABRs and call for more studies in developing effective strategies to achieve stable shortcut nitrogen removal in this energy-efficient configuration.