Single-Cell Sequencing Informs That Mesenchymal Stem Cell Alleviates Renal Injury Through Regulating Kidney Regional Immunity in Lupus Nephritis.

Lupus nephritis (LN) is the common complication of systemic lupus erythematosus. The pathogenesis of LN kidney injury is unclear. In addition to systemic (extrarenal) immune cells, local (intrarenal) immune cells residing in "kidney regional immunity" are momentous in LN. Mesenchymal stem cell (MSC) therapy is effective for LN. However, mechanisms of MSC therapy remains unclear. In this study, we first systematically investigated the effects of MSC on immune cells in kidney regional immunity in LN using single-cell sequencing. We found that MSC reduced proinflammatory central memory CD4+ T cells, cytotoxic tissue-resident memory CD8+ T cells and exhausted CD8+ T cells, increased anti-inflammatory Naive/Effector CD8+ T cells and type 1 regulatory T cells; reduced infiltrating proinflammatory Ly6c hi/inter/lo era2+ macrophages, increased anti-inflammatory resident macrophage and Ly6c lo ear2- macrophage; and reduced long-lived plasma cells and proinflammatory neutrophils and dendritic cells. This study laid a foundation for clinical applications of MSC.

Interaction of "Candidatus Accumulibacter" and nitrifying bacteria to achieve energy-efficient denitrifying phosphorus removal via nitrite pathway from sewage.

To achieve energy-efficient denitrifying phosphorus removal via nitrite pathway from sewage, interaction of "Candidatus Accumulibacter" and nitrifying bacteria was investigated in a continuous-flow process. When nitrite in returned sludge of secondary settler was above 13mg/L, nitrite inhibition on anaerobic P-release of poly-phosphate organisms (PAOs) occurred. Clades IIC and IID were dominant, reaching 3.1%-11.9% of total bacteria. Clade IIC was sensitive to nitrite. Under low concentration of nitrite (<8mg/L), clade IIC primarily contributed to anoxic P-uptake. Clade IID had a strong tolerance to nitrite exposure. At high nitrite level (above 16mg/L), anoxic P-uptake was mainly performed by clade IID due to its strong tolerance to nitrite exposure. Ammonia oxidizing bacteria (AOB), nitrite oxidizing bacteria (NOB) and Accumulibacter interacted through variations of nitrite accumulation. High AOB abundance coupled with inhibition of NOB favored denitrifying phosphorus removal by clade IID. All Accumulibacter lineages were sorted into four clades of Type II. The most dominant ppk1 gene homologs were affiliated with clade IID, accounting for 69% of ppk1 clone library, and thus played an important role in denitrifying phosphorus removal via nitrite pathway.

Influence of nitrite accumulation on "Candidatus Accumulibacter" population structure and enhanced biological phosphorus removal from municipal wastewater.

A modified University of Cape Town (MUCT) process was used to treat real municipal wastewater with low carbon to nitrogen ratio (C/N). To our knowledge, this is the first study where the influence of nitrite accumulation on "Candidatus Accumulibacter" clade-level population structure was investigated during nitritation establishment and destruction. Real time quantitative PCR assays were conducted using the polyphosphate kinase 1 gene (ppk1) as a genetic marker. Abundances of total "Candidatus Accumulibacter", the relative distributions and population structure of the five "Candidatus Accumulibacter" clades were characterized. Under complete nitrification, clade I using nitrate as electron acceptor was below 5% of total "Candidatus Accumulibacter". When the reactor was transformed into nitritation, clade I gradually disappeared. Clade IID using nitrite as electron acceptor for denitrifying phosphorus (P) removal was always the dominant "Candidatus Accumulibacter" throughout the operational period. This clade was above 90% on average in total "Candidatus Accumulibacter", even up to nearly 100%, which was associated with good performance of denitrifying P removal via nitrite pathway. The nitrite concentrations affected the abundance of clade IID. The P removal was mainly completed by anoxic P uptake of about 88%. The P removal efficiency clearly had a positive correlation with the nitrite accumulation ratio. Under nitritation, the P removal efficiency was 30% higher than that under complete nitrification, suggesting that nitrite was appropriate as electron acceptor for denitrifying P removal when treating carbon-limited wastewater.

Integration of denitrifying phosphorus removal via nitrite pathway, simultaneous nitritation-denitritation and anammox treating carbon-limited municipal sewage.

High nutrients removal above 90% from carbon-limited municipal sewage was obtained without adding external carbon source. Achieving nitritation was a prerequisite to improve nutrients removal. Denitrifying phosphorus (P) removal using nitrite as electron acceptor was the key pathway in anoxic zone, where nitrogen removal reached above 60% and average denitrifying P removal was 88%. Simultaneous nitritation/denitritation and anaerobic ammonia oxidation (anammox) possibly contributed to nitrogen removal of 26-36% in aerobic zone. Quantitative PCR assays presented that the abundance of anammox bacteria under nitritation was more than that under complete nitrification. The largest amount of anammox bacteria was 1.32×10(6)copies/gVSS, about 5.6 times increase over a period of 255days. Nitrite concentration of 17mg/L in aerobic zone inhibited anammox bacteria. Quantitative results suggested possible occurrence of anammox. Based on performance of nitritation, combining heterotrophic denitrification with autotrophic nitrogen removal is an effective strategy to improve nutrients removal from carbon-limited wastewater.

Population dynamics of nitrifying bacteria for nitritation achieved in Johannesburg (JHB) process treating municipal wastewater.

Population dynamic of nitrifying bacteria was investigated for nitrogen removal from municipal wastewater. Nitritation was established with nitrite accumulation ratios above 85%. Quantitative PCR indicated that Nitrospira was dominant nitrite oxidizing bacteria (NOB) and Nitrobacter was few. During nitritation achieving, Nitrobacter was firstly eliminated, along with inhibition of Nitrospira bioactivities, then Nitrospira percentage declined and was finally washed out. Nitritation establishment depended on inhibiting and eliminating of NOB rather than ammonia oxidizing bacteria (AOB) enriching. This is the first study where population dynamics of Nitrobacter and Nitrospira were investigated to reveal mechanism of nitritation in a continuous-flow process. Phylogenetic analysis of AOB indicated that Nitrosomonas-like cluster and Nitrosomonas oligotropha were dominant AOB, accounting for 81.6% of amoA gene clone library. Community structure of AOB was similar to that of complete nitrification system with long hydraulic retention time, but different from that of nitritation reactor with low DO concentration.

Nitritation and denitrifying phosphorus removal via nitrite pathway from domestic wastewater in a continuous MUCT process.

Nitritation and denitrifying P removal under mode of nitritation and nitrification was investigated in continuous MUCT process treating domestic wastewater. Nitritation was established through short hydraulic retention time to 6 h and low dissolved oxygen concentration of 0.3-0.5 mg/L. Nitritation was stabilized for 95 days with average nitrite accumulation ratio over 90%. Ammonia and total nitrogen removal under nitritation reached 99% and 83%, respectively, much better than complete nitrification. Real-time quantitative PCR assays presented that cell numbers and percentages of ammonia oxidizing bacteria (AOB) population had a clear correlation with nitrite accumulation ratios. The highest percentage of AOB was 13% of total bacterial population. P removal was mainly completed by denitrifying P removal of about 90% occurring in anoxic zone. The P removal efficiency under nitritation was 30% higher than that under complete nitrification. Denitrifying P removal under nitritation was highly beneficial to the treatment of wastewater with limiting carbon source.