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Mitochondrial replacement therapy (MRT) has been used to prevent maternal transmission of disease-causing mutations in mitochondrial DNA (mtDNA). However, because MRT requires nuclear transfer, it carries the risk of mtDNA carryover and hence of the reversion of mtDNA to pathogenic levels owing to selective replication and genetic drift. Here we show in HeLa cells, mouse embryos and human embryos that mtDNA heteroplasmy can be reduced by pre-labelling the mitochondrial outer membrane of a donor zygote via microinjection with an mRNA coding for a transmembrane peptide fused to an autophagy receptor, to induce the degradation of the labelled mitochondria via forced mitophagy. Forced mitophagy reduced mtDNA carryover in newly reconstructed embryos after MRT, and had negligible effects on the growth curve, reproduction, exercise capacity and other behavioural characteristics of the offspring mice. The induction of forced mitophagy to degrade undesired donor mtDNA may increase the clinical feasibility of MRT and could be extended to other nuclear transfer techniques.

Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis, are widespread in developed countries and gradually increasing in developing countries. Evidences showed that man with CD has a decrease of serum testosterone, but how IBD take effects on testicular testosterone synthesis is not well elucidated. To investigate the effects of IBD on testis, we analyzed testicular metabolome and transcriptome data of the dextran sulfate sodium (DSS) induced IBD mice. As a result, metabolomic data showed that DSS indeed induced androgen decrease in mouse testis. Correspondingly, androgen synthesis associated genes, especially Lhcgr, were down-regulated in DSS testis. From the metabolomic data, we found vitamin intake associated metabolites vitamin B2 and pyridoxamine were significantly decreased, whereas fatty acid metabolism associated molecules N-lauroylglycine and N-decanoylglycine were increased in DSS testis. In addition, we found 8-hydroxy-deoxyguanosine, a DNA oxidative damage marker, and 8-oxoguanine, a molecule responsible for DNA damage repair, were also changed in DSS testis. Simultaneously, our data also showed that DSS up-regulated the expression of meiosis initiation associated gene Stra8 and oxygen transport associated genes in testis. In summary, these results depicted the complex effects of colitis on testis. These metabolites and transcripts changed in DSS testis could be used as potential targets for IBD treatment or symptom relieve.

The co-exposure of antibiotics has important effects on antibiotic resistance genes (ARGs) and microbial community aggregation in wastewater treatment plants (WWTPs). However, it is unclear whether differences in historical antibiotic exposure stress can determine responses of microbes and ARGs to combined antibiotics. By selecting a high concentration (30 mg·L

Mitophagy is a process that selectively degrades mitochondria in cells, and it involves a series of signaling events. Our recent paper shows that the ectopic expression of SQSTM1 and its MAP1LC3B-binding domain (Binding) at the mitochondrial outer membrane, can directly cause mitophagy. To distinguish this mitophagy from others, we called it forced mitophagy. Further results show that the forced mitophagy can degrade half of the mitochondria and their DNA in HeLa cells and mouse embryos. Meanwhile, there are no apparent effects on mitochondrial membrane potential (MMP), reactive oxygen species (ROS), mitosis and embryo development. Thus, the forced mitophagy was examined to selectively degrade mitochondrial carryover in the nuclear donor embryos' mitochondria by pre-labeling with Binding before mitochondrial replacement therapy (MRT). The results show that the forced mitophagy can reduce mitochondrial carryover from an average of 4% to 0.09% compared to the controls in mouse embryos and tissues. In addition, the offspring from MRT mice show negligible effects on growth, reproduction, exercise and behavior. Furthermore, results from human tri-pronuclear embryos show that the forced mitophagy results in undetectable mitochondrial carryover in 77% of embryos following MRT. Therefore, forced mitophagy is efficient and safe for degrading mitochondrial carryover in MRT.

Coagulation process is highly influenced by solution pH, floc breakage, and coagulant aid. In this work, two-stage addition of alum-based coagulants, polyaluminum chloride (PACl) and aluminum sulfate (Al2(SO4)3), was compared to their one-stage addition with the same total dosage. The dose ratio of primary and secondary addition was optimised. The effects of solution pH, floc breakage and dosing timing of coagulant aid of non-ionic polyacrylamide (NPAM) on coagulation efficiency and floc property were investigated. The results showed that two-stage addition of PACl showed less sensitivity with the variation of pH. Compared to PACl, two-stage addition of Al2(SO4)3 was more sensitive to the solution pH, especially when the pH ranged from 7 to 10. For all cases, the presence of floc breakage improved the removal of colloidal particles. The coagulation mechanism of primary coagulant was charge neutralisation, while other mechanism was involved with the secondary addition of coagulant. Compared to one-stage addition, the settling performance of aggregates and particulates removal in two-stage addition was more effective with the variation of dosage or dosing timing of NPAM. The present work provides detailed operating parameters for this coagulation strategy.

This study aimed to explore the impacts of ciprofloxacin (CIP, 0.05-40 mg/L) and copper (3 mg/L) combined pollution on nitrification, microbial community and antibiotic resistance genes (ARGs) in activated sludge system during stress- and post-effect periods. Higher CIP concentration inhibited nitrification and an average of 50% total nitrogen removal occurred under 40 mg/L of CIP pressure. The stress- and post-effects on bacterial diversity and structure were obviously distinct. Abundant genera were more sensitive to combined pollution than rare genera based on full-scale classification and conditionally rare or abundant taxa were keystone taxa in their interactions. Ammonia oxidation genes were inhibited under high CIP level, but some aerobic denitrifying bacteria (Thauera, Comamonas and Azoarcus) and key genes increased. 96 ARG subtypes were detected with complex positive relationships and their potential hosts (abundant-rare-functional genera) changed in two periods. This study highlights the different stress- and post-effects of combined pollution on activated sludge.

Cell division consists of nuclear division (mitosis for somatic cells and meiosis for germ cells) and cytoplasmic division (cytokinesis). Embryonic developments are highly programmed, and thus, each cellular event during early embryo development is stable. For mouse embryos, the first time of mitosis is completed about 22 h after fertilization. However, it remains unclear when the embryo completes its first cytokinesis. Here, we microinjected only one cell in the 2-cell stage mouse embryos with mRNA, which encodes green fluorescence protein (GFP). By monitoring the GFP protein transport dynamics between the two cells, we demonstrated that the first time of cytokinesis in mouse embryos is completed about 15 h after mitosis, namely 37 h after fertilization. In addition, our results indicate that the cytoplasmic protein transport between daughter cells is very effective, which relies on microtubules instead of microfilaments in 2-cell mouse embryos. These results should enrich people’s understanding of the first cell division and cytoskeleton in mouse embryos and then learn more about the mechanisms of early embryo development in mammals.

Effect of copper (Cu) on antibiotic resistance genes (ARGs) and bacterial/archaeal community of activated sludge under gradient increasing (0.5-10 mg/L) or decreasing exposure (10-0.5 mg/L) modes was explored. Here, 29 genes were detected among 48 selected ARGs and mobile gene elements (MGEs). Two exposure modes showed dissimilar effects on ARGs and distribution was more affected by environmental concentrations of Cu, which promoted transmission of ARGs (multiple drug resistance and sulfonamide). Cellular protection was main resistance mechanism, which was less inhibited than efflux pumps. The tnpA-02, as main MGE, interacted closely with ARGs (sul2, floR, etc.). Gradient increasing exposure mode had more effects on bacterial/archaeal structure and composition. Bacteria were main hosts for specific ARGs and tnpA-02, while archaea carried multiple ARGs (cmx(A), adeA, etc.), and bacteria (24.24 %) contributed more to changes of ARGs than archaea (19.29 %). This study clarified the impacts of Cu on the proliferation and transmission of ARGs.

Germ cell-derived genomic structure variants not only drive the evolution of species but also induce developmental defects in offspring. The genomic structure variants have different types, but most of them are originated from DNA double-strand breaks (DSBs). It is still not well known whether DNA DSBs exist in adult mammalian oocytes and how the growing and fully grown oocytes repair their DNA DSBs induced by endogenous or exogenous factors. In this study, we detected the endogenous DNA DSBs in the growing and fully grown mouse oocytes and found that the DNA DSBs mainly localized at the centromere-adjacent regions, which are also copy number variation hotspots. When the exogenous DNA DSBs were introduced by Etoposide, we found that Rad51-mediated homologous recombination (HR) was used to repair the broken DNA. However, the HR repair caused the chromatin intertwined and impaired the homologous chromosome segregation in oocytes. Although we had not detected the indication about HR repair of endogenous centromere-adjacent DNA DSBs, we found that Rad52 and RNA:DNA hybrids colocalized with these DNA DSBs, indicating that a Rad52-dependent DNA repair might exist in oocytes. In summary, our results not only demonstrated an association between endogenous DNA DSBs with genomic structure variants but also revealed one specific DNA DSB repair manner in oocytes.

Based on long-term systematic sampling, information is currently limited regarding the impacts of different air pollution levels on variations of bacteria, fungi and ammonia-oxidizing microorganisms (AOMs) in fine particulate matter (PM2.5), especially their interactions. Here, PM2.5 samples were weekly collected at different air pollution levels in Beijing, China during one-year period. Microbial composition was profiled using Illumina sequencing, and their interactions were further investigated to reveal the hub genera with network analysis. Diversity of bacteria and fungi showed obvious seasonal variations, and the heavy- or severe-pollution levels mainly affected the diversity and composition of bacteria, but not fungi. While, the community structure of both bacteria and fungi was influenced by the combination of air pollution levels and seasons. The most abundant bacterial genera and some genera with highest abundance in heavy- or severe-pollution days were the hub bacteria in PM2.5. Whereas, only the dominant fungi in light-pollution days in winter were the hub fungi in PM2.5. The complex positive correlations of bacterial or fungal pathogens would aggravate the air pollution effects on human health, despite of their low relative abundances. Moreover, the strong co-occurrence and co-exclusion patterns of bacteria and fungi in PM2.5 were identified. Furthermore, the hub environmental factors (e.g., relative humidity and atmospheric pressure) may play central roles in the distributions of bacteria and fungi, including pathogens. Importantly, AOMs showed significant co-occurrence patterns with the main bacterial and fungal genera and potential pathogens, providing possible microbiological evidences for controlling ammonia emissions to effectively reduce PM2.5 pollution. These results highlighted the more obvious air pollution impacts on bacteria than fungi, and the complex bacterial-fungal interactions, as well as the important roles of AOMs in airborne microbial interactions webs, improving our understanding of bioaerosols in PM2.5.

Effects of triclosan (TCS) on performance, microbial community and antibiotic resistance genes (ARGs) during partial denitrification (PD) were investigated in a sequencing moving bed biofilm reactor (SMBBR). TCS inhibited nitrite accumulation; inhibition effect was more obvious as TCS concentration increased from 1 to 5 mg/L, but it could recover. Extracellular polymeric substances contents increased with 1 mg/L TCS addition and decreased a lot at 5 mg/L TCS. Community structure in biofilm was different from that in floccular sludge, but it was similar at 5 mg/L TCS. Illumina sequencing showed that Pseudomonas, Aeromonas, Shewanella and Thauera became dominant genera. Abundance of nirS was stable and higher than that of narG and nosZ. High-throughput qPCR showed that mexF, acrA-02, fabK, etc. were screened at 5 mg/L TCS. IntI1 and tnpA-04 were abundant mobile genetic elements. The study furthers understanding of effects of TCS on PD, bacterial communities and ARGs in SMBBR.

Ammonia-oxidizing microorganisms (AOMs) play important roles in nitrogen removal, but their metabolic activity in winter months in wastewater treatment plants (WWTPs) remains unclear. Here, two full-scale WWTPs were selected, and a total of 48 DNA-based stable isotope probing (DNA-SIP) microcosms of activated sludge samples at different winter months (November-January) and temperatures (13 °C, 25 °C and 37 °C) were constructed to evaluate the temporal heterogeneity and temperature response of active AOMs. The results provided direct evidence that the temporal heterogeneity of AOMs’ activity was not obvious in winter months. In general, ammonia-oxidizing archaea (AOA) and bacteria (AOB) co-participated in the active ammonia oxidation in three winter months at in situ temperature (13 °C) in two WWTPs, and AOA were the dominant active AOMs, even though AOB outnumbered AOA in seed sludge. In contrast, higher peaks of AOA in “heavy” fractions at 25 °C and 37 °C also provided compelling evidence for the dominant contribution of AOA to active ammonia oxidation under higher temperatures. The Illumina sequencing of 13C-DNA obtained from the DNA-SIP microcosms at 13 °C in three winter months further suggest that Candidatus Nitrososphaera evergladensis and Candidatus Nitrosocosmicus exaquare were the dominant active AOA in two WWTPs, while the active AOB were dominated by Nitrosomonas oligotropha. At higher temperatures, active AOA shifted to Ca. N. evergladensis and Candidatus Nitrososphaera gargensis, and Nitrosomonas marina, Nitrosomonas europaea and Nitrosomonas communis dominated in the active AOB. Overall, AOA rather than AOB dominated the active ammonia oxidation in winter months and at higher temperatures in the full-scale WWTPs tested.

Constructed wetlands (CWs) usually exhibit limits in functional redundancy and diversity of microbial community contributing to lower performances of nutrients removal in decentralized domestic sewage treatment. To address this quandary, heterotrophic nitrification-aerobic denitrification (HN-AD) bacteria was added in tidal flow CWs (TFCWs) developing for nitrogen (N) and phosphorus (P) removal. With addition of HN-AD bacteria, TFCWs could be setup more rapidly and obtained better removal efficiencies of 66.9%-70.1% total nitrogen (TN), and 88.2%-92.4% total phosphorus (TP) comparing with control systems (TN: 53.9%; TP: 83.9%) during stable operation. Typical-cycles variations showed that TFCWs with addition of HN-AD bacteria promoted NO3--N and NH4+-N removal respectively under hydraulic retention time (HRT) of 14 h and 8 h with slight NO2--N accumulation. Activated alumina (AA) coupled with HN-AD bacteria decreased P release and relieved its poor removal performance in CWs. Based on metagenomic taxa and functional annotation, Pseudomonas and Thauera played pivotal roles in N removal in TFCWs. Furthermore, gradient oxic environments by 8 h-HRT promoted co-occurrence of heterotrophic nitrifiers (mostly Pseudomonas stutzeri) and autotrophic nitrifiers (mostly Nitrosomonas europaea. and Nitrospira sp.) which potentially accelerated NH4+-N transformation by elevated nitrification and denitrification related genes (e. g. amoABC, hao, napA and nirS genes). Meanwhile, the addition of HN-AD bacteria stimulated nirA and gltD genes of N assimilation processes probably leading to NH4+-N directly removal. The conceptual model of multi-metabolism regulation by HN-AD process highlighted importance of glk, gap2 and PK genes in glycolysis pathway which were vital drivers to nutrients metabolism. Overall, this study provides insights into how ongoing HN-AD bacteria-addition effected microbial consortia and metabolic pathways, serving theoretical basis for its engineered applications of TFCWs in decentralized domestic sewage treatment.

Effects of antibiotics (azithromycin, AZM, 1-40 mg/L) and quorum sensing inhibitor (QSI, 2(5H)-furanone, 1-40 mg/L) combined pollution with environmental concentration of copper on bacterial/archaeal community and antibiotic resistance genes (ARGs) in activated sludge system were explored. QSI inhibited nitrification more obviously than AZM. AZM and QSI were synergistic inhibitions on bacterial diversity, and AZM inhibited bacterial compositions more than QSI. While, QSI had more impacts on archaeal diversity/compositions. Less interactions among bacteria and archaea communities with Aquimonas as keystone genus. Functional differences in bacteria/archaea communities were little, and AZM had more effects on metabolism. AZM mainly affected nitrifying bacteria (Candidatus Nitrospira nitrificans and Nitrosomonas). Specific denitrifying bacteria were enriched by AZM (Brevundimonas, 1.76-31.69%) and QSI (Comamonas, 0.61-9.61%), respectively. AZM enriched ARGs more easily than QSI and they were antagonistic to proliferation of ARGs. Bacteria were main hosts of ARGs (macrolide-lincosamide-streptogramin B, other/efflux, etc.) and archaea (Methanosphaerula, Methanolobus) carried multiple ARGs.

This study aimed to explore the dynamics of microbial communities and antibiotic resistance genes (ARGs) during biofilm formation on polypropylene random (PPR), polyvinyl chloride and stainless steel pipes in domestic hot water system (DHWS), as well as their interactions. Full-scale classification was used to divide abundant and rare genera with 0.1% and 1% as the thresholds. The biofilm community structure presented a temporal pattern, which was mainly determined by conditionally rare or abundant taxa (CRAT) and conditionally rare taxa (CRT). The dynamics of microbial community during biofilm formation were observed, and the effect of pipe material on conditionally abundant taxa (CAT) and CRAT was greater than CRT and rare taxa (RT). CRAT showed the most complex internal associations and were identified as the core taxa. Notably, CRT and RT with low relative abundance, also played an important role in the network. For potential pathogens, 17 genera were identified in this study, and their total relative abundance was the highest (3.6-28.9%) in PPR samples. Enterococcus of CRAT was the dominant potential pathogen in young biofilms. There were 36 more co-exclusion patterns (140) observed between potential pathogens and nonpathogenic bacteria than co-occurrence (104). A total of 38 ARGs were predicted, and 109 negative and 165 positive correlations were detected between them. Some potential pathogens (Escherichia/Shigella and Burkholderia) and nonpathogenic bacteria (Meiothermus and Sphingopyxis) were identified as the possible hosts of ARGs. This study is helpful for a comprehensive understanding of the biofilm microbial community and ARGs, and provides a reference for the management and biosafety guarantee of newly-built DHWS.

Eight disinfection methods were applied to control biofilm contamination in domestic hot water system. The inactivation efficiency, responses of high- (≥1%), mid- (0.1% ~ 1%) and low-abundant taxa (≤0.1%) to disinfection, and interactions within and across three sub-communities were investigated. Ultraviolet was the most effective disinfection method for total bacteria and Escherichia coli, and chlorine dioxide had the highest inactivation efficiency on heterotrophic bacteria, while silver ions exhibited poor performance on all of them. At the phylum level, the responses of microorganisms to eight disinfection methods were different, but Proteobacteria and Firmicutes dominated in most samples. Eight disinfection methods had a greater impact on the proportion of high- and mid-abundant taxa than that of low-abundant taxa, and led to dissimilar transformations of genera among high-, mid- and low-abundant taxa in each sample. High-, mid- and low-abundant taxa of different samples showed similar structures and were roughly clustered into three Groups. Moreover, high-abundant taxa had more complex internal interactions than mid- and low-abundant taxa, and mainly presented co-occurrence patterns. The associations between high- and low-abundant taxa were close, and some low-abundant genera were identified as hub bacteria, such as Paracoccus, Thioalkalispira and Flavitalea. Furthermore, a total of 23 potential pathogens were detected in this study, and they mainly showed positive interactions, with Mycobacteria and Streptococcus as keystone genera. These results highlight the dissimilar responses of high-, mid- and low-abundant taxa to disinfection, and the critical role of some low-abundant genera in the microbial network, as well as the co-occurrence patterns among potential pathogens.

This study investigated the water purification function and mechanism of biofilm in storage tank, with a view to using it as a pretreatment unit for rainwater cleaner production. Shortening the hydraulic retention time (HRT) of storage tank from 12 to 4 h improved the pollutants removal performance and reduced the suspended bacteria counts. The accumulation of abundant taxa and succession of rare taxa were observed with biofilm development. Positive correlations within and across different bacterial taxa were dominant in the network, and some rare genera (Ralstonia and Micropruina) were identified as hub bacteria. Candidatus Nitrospira nitrosa and Nitrospira sp. ENR4 were two identified complete ammonia oxidizers. Denitrifying bacteria tended to enrich and formed more complex interactions over time. The main nitrogen metabolism pathways may be ammonia assimilatory, complete denitrification and dissimilatory/assimilatory nitrate reduction. HRT was negatively correlated with most dominant genera, and contributed 20.35% to the variation of functional taxa. This study highlights the self-purification function and micro-ecology of storage tank, and provides a new insight for its role in rainwater cleaner production process.

The responses of microbial communities and antibiotic resistance genes (ARGs) to azithromycin and copper combined pollution under gradient increasing (from 0.5 to 10 mg/L) and decreasing exposure (from 10 to 0.5 mg/L) modes were investigated. Nitrification was inhibited more obviously under gradient increasing exposure mode. Responses of archaeal community and function structure were more obvious than bacteria under both exposure modes. The dominant bacterial and archaeal compositions (Hyphomicrobium, Euryarchaeota, etc.) were affected by two exposure modes, except some rare archaea (Methanoregula and Methanosarcina). There were more positive correlations between bacteria and archaea, and Nitrospira was keystone genus. Ammonia-oxidizing archaea (0.37-3.06%) and complete ammonia oxidizers (Nitrospira_ENR4) were enriched, and Nitrososphaera_viennensis was closely related to denitrifying genes (napA/B, nosZ, etc.). 50 ARG subtypes were detected and specific ARG subtypes (aac, ImrA, etc.) proliferated in two exposure modes. Bacteria and archaea were common hosts for 24 ARGs and contributed to their shifts.

It is of great significance to introduce regeneration/treatment units into a water system. Regeneration units and treatment units are the same in function and application, but different in destination of the outlet streams. The outlet streams of the regeneration units will be reused/recycled in the water system. The outlet streams of the treatment units will be discharged to environment. This paper provides a review of the development in designing and targeting of continuous water systems involving regeneration/treatment units. The features of Pinch Analysis methods and mathematical programming methods are discussed for the integration of regeneration system, treatment system and total water system separately. For a water system involving regeneration unit, it is addressed that the system can be formed by adding one or more additional source(s), regenerated stream(s), into a water system involving reuse only. The contribution of Liu's group based on the above insight is outlined. Finally, this review offers a guide for future efforts in the integration of water systems involving regeneration/treatment.

This study aimed to investigate the short-term response of abundant-rare genera and antibiotic resistance genes (ARGs) to azithromycin (AZM, 0.05–40 mg/L) and copper (1 mg/L) combined pollution in activated sludge nitrification system at low temperature. Nitrification was as expected inhibited in stress- and post-effects periods under AZM concentration higher than 5 mg/L. Abundant and rare taxa presented dissimilar responses based on full-scale classification. Conditionally rare or abundant taxa (CRAT) were keystone taxa. Relative abundance of ammonia-oxidizing archaea increased, and three aerobic denitrifying bacteria (Brevundimonas, Comamonas and Trichococcus) were enriched (from 9.83% to 68.91% in total). Ammonia nitrogen assimilating into Org-N and denitrification may be nitrogen pathways based on predict analysis. 29 ARGs were found with more co-occurrence patterns and high concentration of AZM (greater than 5 mg/L) caused their proliferation. Importantly, expect for some abundant taxa, rare taxa, potential pathogens and nitrogen-removal functional genera were the main potential hosts of ARGs.

Vacuum ultraviolet/ persulfate (VUV/PS) has been a prospective method for antibiotics removal, however, the enhanced degradation mechanism is still unclear. This study compared the sulfamethazine (SMT) degradation by VUV/PS and ultraviolet/persulfate (UV/PS) processes using a photoreaction system. Results showed that the SMT degradation rate and PS activation rate by VUV/PS was 1.36 times and 1.39 times those of the conventional UV/PS process under the same dosage of PS, respectively. VUV/PS also achieved a high SMT mineralization. SO4•− and HO• played important roles in the degradation of SMT by both processes, while the role of •O2− was little. SMT concentration changed the distributions of 185 nm and 254 nm photons absorbed by solution components and altered the initiated photolysis reaction. Both processes had faster degradation rates at low initial SMT concentrations and the optimum reaction condition was at solution pH of 5. The inhibited level of the SMT degradation in both processes by four anions was in the following order: NO3−> Cl−> HCO3−>SO42 . VUV/PS process was also more efficient than UV/PS for degrading environmental (200 μg/L) and high (5 mg/L) concentration of SMT from three kinds of typical water matrices (tap, river and lake water). Finally, ten photoproducts of SMT degradation by VUV (or UV) were identified, which were mainly the oxidized products of C-N, -NH2 and S-C on SMT molecules, and four degradation pathways were proposed. Overall, these findings could provide useful insights into the application of VUV/PS in efficient antibiotics removal from water.

Objective: The objective of this paper was to investigate differential pathways in sporadic amyotrophic lateral sclerosis (SALS) based on pathway network analysis. Materials and Methods: To achieve this goal, first, differentially expressed genes (DEGs) between SALS and normal controls were identified, and a target network was defined as DEGs correlated interactions from the search tool for the retrieval of interacting genes/proteins (STRING). Second, topological centrality analysis was conducted on the target network to identify hub genes and hub network. Third, pathway network was constructed by taking intersections of Reactome database and STRING protein-protein interaction network. Finally, based on extracting the common interactions between target network, hub network and pathway network, we built randomized network, performed randomization test, and denoted differential pathways and hub differential pathways with P < 0.05. Results: There were 485 DEGs and 627 interactions in the target network. The pathway network was comprised 117,370 interactions. What was more, we found that 217 pathways had intersections with the target network. By accessing randomization test and removing the intersected count

For comprehensive insights into the effects of disinfection strategy on antibiotic resistance genes (ARGs) in pipe wall biofilm to ensure the biosafety of domestic hot water system (DHWS), this study investigated the occurrence, removal and interactions of ARGs, as well as their potential hosts. The shifts in biofilm community composition and microbial functions (level three) were observed under different disinfection strategies. A total of 40 ARG subtypes within seven antibiotic types were predicted. The total gene counts ranged from 6.10 × 104 to 2.31 × 105, and decreased after the chlorine, chlorine dioxide, silver ions (Ag+), ultraviolet (UV), and Ag+-UV disinfection. The ARGs in samples under different disinfection strategies were divided into four groups, and the removal and enrichment of the same ARGs in each group were almost consistent. The complex interactions among ARGs were weakened and altered by disinfection (edges decreased from 237 to 178), with yebQ and marC as the hub ARGs, but positive correlations were still dominant. Moreover, 36 nonpathogenic bacteria, including high- (Blastocatella), mid- (Ornatilinea) and low-abundant genera (Bdellovibrio), as well as 18 potential pathogens (Vibrio and Bacillus) were identified as the potential hosts harboring ARGs. Overall, this study provides some new insights into the occurrence of ARGs and their fate under eight disinfection strategies, which is of great significance for a comprehensive understanding and control of ARGs in DHWS.

This paper reviews concentration potential concepts and their applications in the design of water-using networks (WUNs) with multiple contaminants. The concentration potential concepts were proposed to determine the concentration order of water streams of multiple contaminants based on the overall allocating possibility of source streams to demand streams on the analogy of single contaminant WUNs. The precedence order of water-using processes, which is crucial for the network design, can be effectively identified by the values of Concentration Potential of Demands (CPDs). The concentration potential concepts, which were originally presented for the water networks of fixed contaminant load model, up to now have been successfully used to design a verity of water-using networks. Computing software has also been developed by combining the concentration potential concepts and linear programming approach. The methods proposed based on the concentration potential concepts have the advantages of simple calculation and clear engineering meaning. The results obtained based on the concentration potential concepts are comparable to that obtained by the literature methods. It is shown that the concentration potential concepts are powerful tools for the design of WUNs with multiple contaminants.

This study investigated the effects of secondary chlorination on bacterial regrowth, microbial communities (abundant and rare taxa) and bacterial functions of pipe wall biofilm and bulk water in simulated secondary water supply system (SWSS). Continuous secondary chlorination was more effective than short-term secondary chlorination to control the bacterial regrowth in both biofilm and water samples. Bacterial diversity slightly reduced after continuous secondary chlorination, and 19.27% of the total operational taxonomic units (OTUs) were shared by biofilm and water samples, with Bacillus as the dominant genus. Abundant and rare taxa exhibited different community structures. Proteobacteria and candidate division WPS-1 predominated in abundant and rare phyla were sensitive to chlorine, while Firmicutes, Acidobacteria and Bacteroidetes, exhibited relative strong chlorine resistance. The abundant genera in control sample (e.g., Bosea, Sphingobium and Gemmata) exhibited poor tolerance to chlorine, while Bacillus in biofilm and Defluviimonas in water were the main chlorine-resistant genera. Moreover, the composition of rare genera in each sample was obviously different. Furthermore, a total of 18 potential pathogens were detected with Pseudomonas as the dominant genus, most of which were significantly reduced after disinfection. There were mainly positive interactions among potential pathogenic bacteria, with Enterococcus, Legionella and Vibrio as the hub genera as revealed by network analysis. Similar bacterial functions in both biofilm and water were observed with metabolism as the predominant bacterial function, while, human disease function only accounted for 1.07% of bacterial functions. These results highlighted the importance of continuous secondary chlorination for controlling biosafety of SWSS and identified the dissimilar responses of abundant and rare bacteria to the disinfection, as well as the co-occurrence patterns among potential pathogens, improving our understanding of bacterial communities in SWSS.

In a coagulation-flocculation process, optimal separation of the resultant aggregates plays a decisive role on coagulation performance and provides a lower burden for subsequent treatment units. This separation highly depends on the stability of the micro-flocs formed during the initial, rapid stage of coagulation. In this work, a two-stage addition of aluminium sulphate (alum, Al2(SO4)3) was employed by adding 0.04 and 0.08 mM Al2(SO4)3 at the beginning and the end of rapid mixing, respectively. The coagulation performance and floc characteristics were compared to conventional single addition with the same total coagulant dosage, and the effects of variable rapid-mixing speeds (160–850 rpm) and duration time (10–120 s) were investigated. The results showed that the residual turbidity of two-stage coagulant addition was 85.1% lower than single addition when applied at a mixing speed of 580 rpm and a duration time of 120 s. The underlying coagulation mechanism revealed that the two-step addition more effectively neutralized colloids and formed larger aggregates that settled better and could more easily be removed. Moreover, the aggregates were less firm, which was attributed to different interactions among the micro-flocs, the second addition of Al2(SO4)3 and destabilized colloids. The present work provides data to broaden the window of rapid-mixing environments for more effective coagulation.

This study investigated the influence of C/N ratios and tidal strategies on nitrogen removal and bacterial communities in two pilot-scale tidal flow constructed wetlands (TFCWs) with simultaneous nitrification–denitrification process. Heterotrophic nitrification aerobic denitrification (HNAD) was the main nitrogen transformation pathway in both TFCWs. High C/N ratios and effluent circulation at low temperature promoted HNAD in TFCWs with high nitrogen removal efficiencies (72.6%–95.5% for NH4+-N and 70.9%~91.8% for TN). Effluent circulation had more influence on bacterial community structure and diversity than C/N ratios. Among 16 detected genera related to nitrogen removal, HNAD bacteria (HNADB) were abundant. Especially, some dominant HNADB (e.g. Aeromonas, Hydrogenophage and Gemmobacter) were core genera, showing positive interactions with other genera related to nitrogen removal. Tidal strategies had more contribution to the shifts in these genera than C/N ratios. This study highlights the importance of HNADB in pilot-scale TFCWs and their responses to C/N ratios and tidal strategies.

This study explored the application of shale ceramsite (SC) overlaid onto active alumina (AA) to function as a double-layer substrate in tidal flow constructed wetland (TFCW, SC-AA-TFCW) for decentralized domestic sewage treatment. This was compared to AA or SC substrate alone (AA-TFCW or SC-TFCW) for nitrogen removal, variation of dissolved oxygen and porosity in TFCWs, as well as structure of bacterial communities at varied hydraulic load (HL) of 0.204–2.448 m3/m2 d with time ratio of the wet and dry phase of 3:1. The results demonstrate that SC-AA-TFCW removed 86% NH4+-N and 79% total nitrogen at HL of 0.612 m3/m2 d, which was better than AA-TFCW(76%) or SC-TFCW(49%). The higher nitrogen removal performance in SC-AA-TFCW was mainly attributed to enhanced oxygen transportation due to non-uniform flow field and irregular gap distribution in layered structure, as well as less pore blockage during long-term operation. Denitrifying bacteria including Dechloromonas, Acidovorax, Chryseobacterium and Thermomonas species took up 32% of the microbiome in SC-AA-TFCW, which was higher than in AA-TFCW (17%) and SC-TFCW (7.7%). This study highlighted the importance of layered structures and determined an optimal HL of TFCW to achieve an efficient and stable nitrogen removal for domestic sewage treatment.

In this work, the adsorption characteristics, including adsorption kinetic, isotherm and thermodynamics of chloramphenicol (CAP) onto powdered activated carbon (PAC), were carried out, and the feasibility of using ultrasound to regenerate saturated PAC in aqueous solution was evaluated. The adsorption results demonstrated that the adsorption mechanism was a complex process including surface adsorption, external liquid membrane diffusion and intraparticle diffusion as well, and the adsorption process was endothermic and non-spontaneous. The optimal conditions for PAC regeneration were as follows: acoustic density of 0.36 W/mL, saturated carbon dosage of 1.0 g/L and pH value of 10.36. The analysis of thermogravimetric analysis (TGA), Fourier transform infrared spectrometry (FTIR), Brunauer–Emmett–Teller (BET) surface area, pore size distribution and scanning electron microscopy (SEM) of PAC samples revealed that ultrasound mainly acted on surface functionalities, meso-pores and macro-pores of PAC through hydroxyl radical oxidization, high-pressure shock waves and high-speed microjets due to cavitation effect. This study highlighted that ultrasound could be efficiently desorbing CAP from saturated PAC. Practical applications of this method for PAC regeneration with complex natural matrices under environmentally realistic conditions were conducted and the adsorption capacity of the regenerated PAC decreased.

Objective To explore correlations between body mass index (BMI), preoperative systemic immune-inflammation index (SII) and endocrine therapy resistance, and evaluate BMI and SII as predictors of resistance, in patients with luminal breast cancer. Methods This retrospective study included patients with luminal breast cancer who underwent endocrine therapy at Hebei General Hospital. Relationships between BMI and SII subgroups, and clinicopathological parameters were analysed using χ2-tests. Disease-free survival was assessed using Log-rank statistics. Multivariate analysis of factors related to disease progression were analysed using Cox proportional hazards model. Results Out of 161 patients, those with normal BMI and low SII had significantly lower endocrine resistance rates versus those with high BMI and SII, and BMI was significantly positively correlated with SII. High BMI or SII was associated with significantly lower disease-free survival rates. Hazard ratios for disease progression risk were 6.036, 3.508 and 1.733, for SII, BMI and TNM stage, respectively. Conclusion In patients with luminal breast cancer, high BMI (>23 kg/m2) and SII (>518 × 109/L) levels may predict high endocrine resistance rates. BMI, SII and TNM stage were independent prognostic factors for endocrine therapy resistance.

This study investigated the bacterial communities, metabolic functions, antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) in two alternating anaerobic/aerobic biological filters (A/O-BFs) treating saline seafood wastewater (SSW). Firmicutes was the most abundant phylum in both systems, and halophilic and alkaliphilic bacteria were largely enriched. 15 potential pathogens were obtained. Metabolism was the predominant bacterial function. 49 ARGs and 7 MRGs were detected, and the total abundance of ARGs increased while that of MRGs decreased. Clear shifts in bacterial structure and function, ARGs and MRGs were observed in both systems and at different heights. Co-occurrence of ARGs and MRGs and their hosts were identified. ARGs and MRGs mainly negatively correlated with bacterial functions, which were also the important contributors to shifts in bacterial communities and functions. This study highlights the importance of investigating ARGs and MRGs in SSW treatment systems and their complex interactions with bacterial communities and functions.

Silver-loaded stainless steel (Ag-SS) was applied in domestic hot water system (DHWS) to control the biofilm contamination. The antibacterial properties of Ag-SS, as well as the bacterial communities, potential pathogens and antibiotic resistance genes (ARGs) of pipe wall biofilm were investigated, with SS as control. Ag-SS maintained a high antibacterial efficiency on heterotrophic bacteria (70.60 ± 13.22 %) and Escherichia coli (73.56 ± 10.62 %) by contact bacteriostasis. Dominant phyla exhibited a lower relative abundance in Ag-SS than SS. The bacteria were further classified into abundant (≥ 1 %), moderately abundant (0.1∼1 %) and rare (≤ 0.1 %) taxa to investigate their responses to silver. There were 15.33 % of shared operational taxonomic units (OTUs) belonged to abundant taxa, while most unique OTUs (> 80 %) of each sample were identified as rare taxa. As the primary abundant genera, Mesorhizobium and Bradyrhizobium exhibited resistant and sensitive to silver, respectively. Most dominant moderately abundant and rare genera were resistant to silver. Moreover, among 19 detected potential pathogens, Legionella, Parachlamydia and Aeromonas were sensitive to silver, while Pseudomonas and Acinetobacter were resistant to silver. Furthermore, a total of 48 ARGs were detected and they exhibited similar distributions in both samples. The total abundance of ARGs in Ag-SS increased by 0.08 fold compared with that in SS, with efflux pumps as the main resistance mechanisms. This study highlights the different responses of abundant, moderately abundant and rare taxa to silver, and the occurrences of ARGs, confirming that Ag-SS was an effective disinfection strategy for biosafety protection of DHWS.

The dynamics of bacterial communities in a full-scale wastewater treatment plant (WWTP) were investigated using Illumina MiSeq sequencing and PICRUSt (phylogenetic investigation of communities by reconstruction of unobserved states) over a one-year period. Results showed that the temporal dynamics of structure, diversity and abundance of bacterial community were not obvious. The persistent species had low diversity but high relative abundance. Dechloromonas, Thauera, Nitrosomonas and Nitrospira were the four dominant persistent genera. The intermittent and transient genera showed different dynamics with persistent genera. Variation partitioning analysis suggested that water quality indexes (13.40%) had the greatest contribution to bacterial community variation, followed by temperature (9.20%). Quantitative polymerase chain reaction analysis revealed the stable abundances of nitrifying and denitrifying bacteria, and the occurrence of complete ammonia oxidizers (Comammox) in the full-scale WWTP. Functional prediction showed that the bacterial functional compositions were also relatively stable, and metabolism was the most dominant functional category. Many genes involved in the nitrogen metabolism pathway were predicted to be present with high gene counts, e.g., nirB, nirD, nasA, norB, nirK, nosZ and nifH. Most of these genes were predicted to be mainly contributed by Rhizobiales, Burkholderiales, Rhodocyclales and Actinomycetales. Overall, the composition and function of bacterial community in a long-term monitoring were relatively stable, which is important for maintaining the high wastewater treatment capability in full-scale WWTPs.