Habitat-specific regulation of bacterial community dynamics during phytoplankton bloom succession in a subtropical eutrophic lake.

Phytoplankton blooms, an important indicator of severe eutrophication, are a globally significant consequence of anthropogenic activities and climate change on freshwater lakes. Shifts in microbial communities during phytoplankton blooms have been extensively investigated, yet we have a limited understanding of how distinct assembly processes underlying the temporal dynamics of freshwater bacterial communities within different habitats respond to the succession of phytoplankton blooms. To address this knowledge gap, we collected both water and sediment samples in a subtropical eutrophic lake over a complete period of phytoplankton blooms to assess the dynamics of bacterial communities and the temporal shifts in assembly processes. Our results showed that phytoplankton blooms strongly altered the diversity, composition, and coexistence patterns of both planktonic and sediment bacterial communities (PBC and SBC), but the successional patterns differed between PBC and SBC. PBC were less temporally stable under bloom-induce disturbances, with higher variations in temporal dynamics and greater sensitivity to environmental fluctuations. Furthermore, the temporal assembly patterns of bacterial communities in both habitats were mainly driven by homogeneous selection and ecological drift. In the PBC, the role of selection decreased over time, while ecological drift became increasingly important. Conversely, in the SBC, the relative impact of selection and ecological drift on community assemblages fluctuated less over time, with selection remaining the dominant process throughout the bloom.

Nrf2 protects against renal fibrosis induced by chronic cadmium exposure in mice.

Environmental cadmium (Cd) exposure is a serious public health concern, as the kidney is the primary target for Cd exposure. The present study aimed to investigate the role and underlying mechanisms of nuclear factor erythroid-derived 2-like 2 (Nrf2) in renal fibrosis induced by chronic Cd exposure. Nrf2 knockout (Nrf2-KO) mice and their wild-type littermates (Nrf2-WT) were exposed to 100 or 200 ppm Cd in drinking water for up to 16 or 24 weeks. Following the Cd exposures, Nrf2-KO mice showed elevated urinary neutrophil gelatinase-associated lipocalin (NGAL) and BUN levels compared to Nrf2-WT mice. Masson's trichrome staining and expression of fibrosis-associated proteins revealed that more severe renal fibrosis occurred in Nrf2-KO than that in Nrf2-WT mice. Renal Cd content in the Nrf2-KO mice exposed to 200 ppm Cd was lower than that in Nrf2-WT mice, which might be a consequence of the severe renal fibrosis in the Nrf2-KO mice. Mechanistic studies showed that Nrf2-KO mice exhibited higher levels of oxidative damage, lower antioxidant levels, and more regulated cell death, apoptosis in particular, than those in Nrf2-WT mice caused by Cd exposure. In conclusion, Nrf2-KO mice were more prone to develop renal fibrosis induced by chronic Cd exposure, partially due to a weakened antioxidant, detoxification capacity and increased oxidative damage.

Coexistence of cryoglobulinemia and ANCA-associated vasculitis in a chronic brucellosis patient -a case report and literature review.

BACKGROUND: The renal involvement of brucellosis is not common. Here we reported a rare case of chronic brucellosis accompanied by nephritic syndrome, acute kidney injury, the coexistence of cryoglobulinemia and antineutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) superimposed on iliac aortic stent implantation. The diagnosis and treatment of the case are instructive. CASE PRESENTATION: A 49-year-old man with hypertension and iliac aortic stent implantation was admitted for unexplained renal failure with signs of nephritic syndrome, congestive heart failure, moderate anemia and livedoid change in the left sole with pain. His past history included chronic brucellosis and he just underwent the recurrence and completed the 6 weeks of antibiotics treatment. He demonstrated positive cytoplasmic/proteinase 3 ANCA, mixed type cryoglobulinemia and decreased C3. The kidney biopsy revealed endocapillary proliferative glomerulonephritis with a small amount of crescent formation. Immunofluorescence staining revealed only C3-positive staining. In accordance with clinical and laboratory findings, post-infective acute glomerulonephritis superimposed with AAV was diagnosed. The patient was treated with corticosteroids and antibiotics and sustained alleviation of renal function and brucellosis was achieved during the course of a 3-month follow-up. CONCLUSIONS: Here we describe the diagnostic and treatment challenge in a patient with chronic brucellosis related glomerulonephritis accompanied by the coexistence of AAV and cryoglobulinemia. Renal biopsy confirmed the diagnosis of postinfectious acute glomerulonephritis overlapping with ANCA related crescentic glomerulonephritis, which was not ever reported in the literature. The patient showed a good response to steroid treatment which indicated the immunity-induced kidney injury. Meanwhile, it is essential to recognize and actively treat the coexisting brucellosis even when there are no clinical signs of the active stage of infection. This is the critical point for a salutary patient outcome for brucellosis associated renal complications.

IL-18 deficiency ameliorates the progression from AKI to CKD.

Inflammation is an important factor in the progression from acute kidney injury (AKI) to chronic kidney disease (CKD). The role of interleukin (IL)-18 in this progression has not been examined. We aimed to clarify whether and how IL-18 limits this progression. In a folic acid induced renal injury mouse model, we studied the time course of kidney injury and renal IL-18 expression. In wild-type mice following injection, renal IL-18 expression increased. In parallel, we characterized other processes, including at day 2, renal tubular necroptosis assessed by receptor-interacting serine/threonine-protein kinase1 (RIPK1) and RIPK3; at day 14, transdifferentiation (assessed by transforming growth factor ß1, vimentin and E-cadherin); and at day 30, fibrosis (assessed by collagen 1). In IL-18 knockout mice given folate, compared to wild-type mice, tubular damage and necroptosis, transdifferentiation, and renal fibrosis were attenuated. Importantly, IL-18 deletion decreased numbers of renal M1 macrophages and M1 macrophage cytokine levels at day 14, and reduced M2 macrophages numbers and macrophage cytokine expression at day 30. In HK-2 cells, IL-18 knockdown attenuated necroptosis, transdifferentiating and fibrosis.In patients with tubulointerstitial nephritis, IL-18 protein expression was increased on renal biopsies using immunohistochemistry. We conclude that genetic IL-18 deficiency ameliorates renal tubular damage, necroptosis, cell transdifferentiation, and fibrosis. The renoprotective role of IL-18 deletion in the progression from AKI to fibrosis may be mediated by reducing a switch in predominance from M1 to profibrotic M2 macrophages during the process of kidney repair.

circMTND5 Participates in Renal Mitochondrial Injury and Fibrosis by Sponging MIR6812 in Lupus Nephritis.

Recent studies have focused on nuclear-encoded circular RNAs (circRNAs) in kidney diseases, but little is known about mitochondrial circRNAs. Differentially expressed circRNAs were analyzed by RNA deep sequencing from lupus nephritis (LN) biopsies and normal human kidneys. In LN renal biopsies, the most downregulated circRNA was circMTND5, which is encoded in the mitochondrial genome. We quantitated circMTND5 by qPCR and localized by fluorescence in situ hybridization (FISH). Mitochondrial abnormalities were identified by electron microscopy. The expression of mitochondrial genes was decreased, and the expression of profibrotic genes was increased on qPCR and immunostaining. RNA binding sites for MIR6812 and circMTND5 were predicted. MIR6812 expression was increased by FISH and qPCR. In HK-2 cells and its mitochondrial fraction, the role of circMTND5 sponging MIR6812 was assessed by their colocalization in mitochondria on FISH, RNA immunoprecipitation, and RNA pulldown coupled with luciferase reporter assay. circMTND5 knockdown upregulated MIR6812, decreased mitochondrial functional gene expression, and increased profibrotic gene expression. Overexpression of circMTND5 reversed these effects in hTGF-ß stimulated HK-2 cells. Similar effects were observed in HK-2 cells with overexpression and with knockdown of MIR6812. We conclude that circMTND5 alleviates renal mitochondrial injury and kidney fibrosis by sponging MIR6812 in LN.

LNA-anti-miR-150 alleviates renal interstitial fibrosis by reducing pro-inflammatory M1/M2 macrophage polarization.

Renal interstitial fibrosis (RIF) is a common pathological feature contributing to chronic injury and maladaptive repair following acute kidney injury. Currently, there is no effective therapy for RIF. We have reported that locked nuclear acid (LNA)-anti-miR-150 antagonizes pro-fibrotic pathways in human renal tubular cells by regulating the suppressor of cytokine signal 1 (SOCS1)/Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. In the present study, we aimed to clarify whether LNA-anti-miR-150 attenuates folic acid-induced RIF mice by regulating this pathway and by reducing pro-inflammatory M1/M2 macrophage polarization. We found that renal miR-150 was upregulated in folic acid-induced RIF mice at day 30 after injection. LNA-anti-miR-150 alleviated the degree of RIF, as shown by periodic acid-Schiff and Masson staining and by the expression of pro-fibrotic proteins, including alpha-smooth muscle actin and fibronectin. In RIF mice, SOCS1 was downregulated, and p-JAK1 and p-STAT1 were upregulated. LNA-anti-miR-150 reversed the changes in renal SOCS1, p-JAK1, and p-STAT1 expression. In addition, renal infiltration of total macrophages, pro-inflammatory M1 and M2 macrophages as well as their secreted cytokines were increased in RIF mice compared to control mice. Importantly, in folic acid-induced RIF mice, LNA-anti-miR-150 attenuated the renal infiltration of total macrophages and pro-inflammatory subsets, including M1 macrophages expressing CD11c and M2 macrophages expressing CD206. We conclude that the anti-renal fibrotic role of LNA-anti-miR-150 in folic acid-induced RIF mice may be mediated by reducing pro-inflammatory M1 and M2 macrophage polarization via the SOCS1/JAK1/STAT1 pathway.

Contrasting assembly mechanisms explain the biogeographic patterns of benthic bacterial and fungal communities on the Tibetan Plateau.

The Tibetan Plateau characterized by high altitude and low temperature, where a great number of lakes are located, is a hotspot of global biodiversity research. Both bacterial and fungal communities are vital participants of biogeochemical cycling in lake ecosystems. However, we know very little about the large-scale biogeographic patterns and the underlying assembly mechanisms of lake benthic microbial communities on the Tibetan Plateau. To investigate the biogeographic patterns and their underlying assembly mechanisms of benthic bacterial and fungal communities, we collected sediment samples from 11 lakes on the Tibetan Plateau (maximum geographic distance between lakes over 1100 km). Benthic community diversity and composition were determined using the high-throughput sequencing technique. Our results indicated that there were contrasting distance-decay relationships between benthic bacterial and fungal communities on a regional scale. Benthic bacterial communities showed a significant distance-decay relationship, whereas no significant relationship was observed for benthic fungal communities. Deterministic processes dominated the bacterial community assembly, whereas fungal community assembly was more stochastic. pH was a dominant factor in influencing the geographic distribution of benthic microbial communities. Co-occurrence network analysis revealed that bacterial communities showed higher complexity and greater stability than those of the fungal communities. Taken together, this study contributes to a novel understanding of the assembly mechanisms underlying the biogeographic distribution of plateau benthic bacterial and fungal communities at a large scale.

Disentangling the assembly mechanisms of bacterial communities in a transition zone between the alpine steppe and alpine meadow ecosystems on the Tibetan Plateau.

Alpine meadows and alpine steppes are two major grassland types distributed on the Tibetan Plateau. Due in large part to the differences in hydrothermal and nutrient conditions following the thawing of lakeshore permafrost, alpine meadows and alpine steppes which are characterized by disparate above- and below-ground biomass, could emerge together in the grassland transition zone between meadows and steppes of the Tibetan Plateau. Bacterial communities are essential components of alpine grassland ecosystems and respond rapidly to environmental changes. Despite their ecological significance, it remains poorly elucidated whether and how the assembly patterns of bacterial communities differed between alpine meadows and alpine steppes. Here, to disentangle the assembly mechanisms of bacterial communities from alpine meadows and alpine steppes, we collected samples from three diverse habitats (i.e., sediments, rhizosphere soils and bulk soils) in both alpine meadow and steppe ecosystems on the Tibetan Plateau. Our results indicated that in both meadows and steppes, rhizosphere bacterial communities exhibited higher alpha-diversity but lower beta-diversity compared to the bacterial communities in sediments and bulk soils. However, the close relationships of bacterial communities between different habitats weakened from meadows to steppes. Null model analysis indicated that the importance of environmental selection shaping bacterial community assemblages in all habitats decreased from meadows to steppes, whereas the role of dispersal limitation showed an opposite pattern. Moreover, pH was the primary driver of phylogenetic turnover of bacterial communities in the steppes across all habitats, whereas the dominant drivers of phylogenetic turnover of bacterial communities in meadows varied with habitat types. Overall, our findings provide novel insights into understanding the differences in microbial communities between meadows and steppes in the grassland transition zone on the Tibetan Plateau.

Eutrophication in subtropical lakes reinforces the dominance of balanced-variation component in temporal bacterioplankton community heterogeneity by lessening stochastic processes.

Unveiling the rules of bacterioplankton community assembly in anthropogenically disturbed lakes is a crucial issue in aquatic ecology. However, it is unclear how the ecological processes underlying the seasonally driven bacterioplankton community structure respond to varying degrees of lake eutrophication. We, therefore, collected water samples from three subtropical freshwater lakes with various trophic states (i.e. oligo-mesotrophic, mesotrophic, and eutrophic states) on a quarterly basis between 2017 and 2018. To innovatively increase our understanding of bacterioplankton community assembly along the trophic state gradient, the total bacterioplankton community dissimilarity was subdivided into balanced variation in abundances and abundance gradients. The results indicated that balanced-variation component rather than abundance-gradient component dominated the total temporal ß-diversity of bacterioplankton communities across all trophic categories. Ecological stochasticity contributed more to the overall bacterioplankton community assembly in the oligo-mesotrophic and mesotrophic lakes than in the eutrophic lake. The reduced bacterioplankton network complexity at the eutrophic level was closely associated with the enhancement of environmental filtering, showing that bacterioplankton communities in eutrophic lakes are likely to be less stable and more vulnerable to water quality degradation. Together, this study offers essential clues for biodiversity conservation in subtropical lakes under future intensified eutrophication.

Co-occurrence of IgA nephropathy and IgG4-Tubulointersitial nephritis effectively treated with tacrolimus: a case report.

BACKGROUND: Cases of concurrent immunoglobulin A nephropathy (IgAN) and IgG4-related tubulointerstitial nephritis (IgG4-TIN) are rare and previous case reports have lacked important data. KDIGO suggests a treatment with systemic glucocorticoids in IgAN patients. Glucocorticoids are recommended as the first-line therapy for IgG4-TIN. The use of tacrolimus as a long-term maintenance treatment has not been described. We report the case of a man who developed IgAN and IgG4-TIN without abnormalities in extra-renal tissue, without renal function abnormalities or impairment as well, and was treated by tacrolimus as a long-term maintenance during 45 months follow-up. CASE PRESENTATION: A 56-year-old Chinese man first presented to our hospital with the chief complaint of foamy urine for 1 year and hematuria for 3 months, with a medical history of hypertension. Testing revealed a notable increase in serum IgG4 level without abnormalities in renal function or imaging, or in dysfunction other organs. Renal biopsy showed mesangial extracellular matrix proliferation, increased mesangial cell numbers and infiltration of plasma cells. Immunofluorescence showed mesangial positivity for IgA and C3. Immunohistochemistry staining showed widespread IgG4 and increased CD38 and CD138 expression. Electron microscopy showed immune complexes located on the tubular basement membrane. He was diagnosed with IgAN and IgG4-TIN. He received glucocorticoids, leflunomide and tacrolimus to induce remission. He was given tacrolimus as long-term maintenance treatment. When tacrolimus was temporarily withdrawn, proteinuria recurred. After resuming tacrolimus therapy, he again entered complete remission. After 45 months of therapy, he remains in complete remission and the serum IgG4 level is normal. CONCLUSIONS: The finding of concurrent IgAN and IgG4-TIN without abnormalities in renal function, imaging or extra-renal tissue is rare and their coexistence may be coincidental. Long-term treatment with tacrolimus proved effective and he has remained in remission during 45 months follow-up.

Nrf2 deficiency aggravates the kidney injury induced by subacute cadmium exposure in mice.

Cadmium (Cd) is a heavy metal pollutant that adversely effects the kidney. Oxidative stress and inflammation are likely major mechanisms of Cd-induced kidney injury. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is crucial in regulating antioxidant and inflammatory responses. To investigate the role of Nrf2 in the development of subacute Cd-induced renal injury, we utilized Nrf2 knockout (Nrf2-KO) and control mice (Nrf2-WT) which were given cadmium chloride (CdCl2, 1 or 2 mg/kg i.p.) once daily for 7 days. While subacute CdCl2 exposure induced kidney injury in a dose-dependent manner, after the higher Cd dosage exposure, Nrf2-KO mice showed elevated blood urea nitrogen (BUN) and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels compared to control. In line with the findings, the renal tubule injury caused by 2 mg Cd/kg, but not lower dosage, in Nrf2-KO mice determined by Periodic acid-Schiff staining was more serious than that in control mice. Further mechanistic studies showed that Nrf2-KO mice had more apoptotic cells and severe oxidative stress and inflammation in the renal tubules in response to Cd exposures. Although there were no significant differences in Cd contents of tissues between Cd-exposed Nrf2-WT and Nrf2-KO mice, the mRNA expression of Nrf2 downstream genes, including heme oxygenase 1 and metallothionein 1, were significantly less induced by Cd exposures in the kidney of Nrf2-KO compared with Nrf2-WT mice. In conclusion, Nrf2-deficient mice are more sensitive to kidney injury induced by subacute Cd exposure due to a muted antioxidant response, as well as a likely diminished production of specific Cd detoxification metallothioneins.

circHIPK3 Exacerbates Folic Acid-Induced Renal Tubulointerstitial Fibrosis by Sponging miR-30a.

Renal tubulointerstitial fibrosis is a common pathological feature of progressive chronic kidney disease (CKD), and current treatment has limited efficacy. The circular RNA circHIPK3 is reported to participate in the pathogenesis of various human diseases. However, the role of circHIPK3 in renal fibrosis has not been examined. In this study, we aimed to determine whether and how circHIPK3 might participate in the pathogenesis of renal fibrosis. Mice received a peritoneal injection of folic acid (250 mg/kg). Of note, 30 days later, renal fibrosis was present on periodic acid-Schiff (PAS) and Masson staining, and mRNA and protein of profibrotic genes encoding fibronectin (FN) and collagen 1 (COL1) were increased. Renal circHIPK3 was upregulated, while miR-30a was downregulated, assessed by quantitative PCR (qPCR) and fluorescence in situ hybridization (FISH). The expression of transforming growth factor beta-1 (TGF-ß1) was increased by qPCR analysis, immunoblotting, and immunofluorescence. Renal circHIPK3 negatively correlated with miR-30a, and kidney miR-30a negatively correlated with TGF-ß1. Target Scan and miRanda algorithms predicted three perfect binding sites between circHIPK3 and miR-30a. We found that circHIPK3, miR-30a, and TGF-ß1 colocalized in the cytoplasm of human tubular epithelial cells (HK-2 cells) on FISH and immunofluorescence staining. We transfected circHIPK3 and a scrambled RNA into HK-2 cells; miR-30a was downregulated, and the profibrotic genes such as TGF-ß1, FN, and COL1 were upregulated and assessed by qPCR, immunoblotting, and immunofluorescence staining. Third, the upregulation of circHIPK3, downregulation of miR-30a, and overproduction of profibrotic FN and COL1 were also observed in HK-2 cells exposed to TGF-ß1. Finally, renal biopsies from patients with chronic tubulointerstitial nephritis manifested similar expression patterns of circHIPK3, miR-30a, and profibrotic proteins, such as TGF-ß1, FN, and COL1 as observed in the experimental model. A feed-forward cycle was observed among circHIPK3, miR-30a, and TGF-ß1. Our results suggest that circHIPK3 may contribute to progressive renal fibrosis by sponging miR-30a. circHIPK3 may be a novel therapeutic target for slowing CKD progression.

miR-150-Based RNA Interference Attenuates Tubulointerstitial Fibrosis through the SOCS1/JAK/STAT Pathway In Vivo and In Vitro.

We investigated whether microRNA-150 (miR-150)-based RNA interference (RNAi) ameliorates tubular injury and tubulointerstitial fibrosis. Mice injected with folic acid developed tubulointerstitial fibrosis at day 30. miR-150 levels were increased at day 7 and peaked at day 30. At day 30, protein levels of α-smooth muscle actin, fibronectin (FN), and collagen 1 (COL-1) were increased, while suppressor of cytokine signal 1 (SOCS1) was decreased. Kidneys manifested increased macrophage numbers and increased expression of potential mediators: interferon-γ, interleukin-6, and tumor necrosis factor-α. Locked nucleic acid-anti-miR-150, started prior to or after tubular injury and administered twice weekly for 4 weeks, reversed renal inflammation and fibrosis. In HK-2 cells, co-culture with macrophages increased miR-150 expression and decreased SOCS1. Janus kinase (JAK) and signal transducer and activators of transcription (STAT) pathway-related proteins p-JAK1, p-JAK2, p-STAT1, p-STAT3, and pro-fibrotic genes encoding α-smooth muscle actin, FN, and COL-1 were all upregulated. The miR-150 antagonist reversed these transcriptional changes. Lastly, in renal biopsies from patients with chronic interstitial fibrosis, renal miR-150, and pro-fibrotic gene expression and macrophage numbers were increased, while SOCS1 expression was decreased. In conclusion, miR-150-based RNAi is as a potential novel therapeutic agent for tubulointerstitial fibrosis, suppressing the SOCS1/JAK/STAT pathway and reducing macrophage influx.

CircZNF609 is involved in the pathogenesis of focal segmental glomerulosclerosis by sponging miR-615-5p.

As a set of distinct syndromes, focal segmental glomerulosclerosis (FSGS) is the most common cause of adult nephrotic syndrome with diverse mechanisms. We recently found that expression of the circular RNA circZNF609 is increased in renal biopsies of lupus nephritis patients. In the present study, we aimed to determine whether circZNF609 participates in the pathogenesis of FSGS in mice given Adriamycin. In FSGS mice, circZNF609 was upregulated while miR-615-5p was downregulated in FSGS mice analyzed by qPCR and fluorescence in situ hybridization (FISH). Expression of podocyte proteins Wilms tumor 1 (WT1) and podocin were decreased, while expression of collagen 1 (COL1) and transforming growth factor-beta1 (TGF-ß1) were increased on Western blotting. Renal circZNF609 levels were positively correlated and miR-615-5p levels were negatively correlated with the degree of podocyte injury and renal fibrosis. Importantly, circZNF609 and miR-615-5p co-localized to glomeruli and tubules on FISH. Perfect match seeds were found between circZNF609 and miR-615-5p and COL1 mRNA, leading us to explore mechanisms of circZNF609 in bovine serum albumin (BSA) stimulating HK-2 cells, which model the toxicity of proteinuria on tubular cells. In vitro studies, circZNF609 increased and miR-615-5p decreased after BSA treatment and were negatively correlated with each other. COL1 and TGF-ß1 were both upregulated and negatively correlated with miR-615-5p. Lastly, circZNF609 expression increased in glomeruli and tubules of FSGS patient renal biopsies. We conclude that circZNF609 may play an important role in FSGS by sponging miR-615-5p.

Disentangling the seasonal co-occurrence patterns and ecological stochasticity of planktonic and benthic bacterial communities within multiple lakes.

Both the planktonic bacterial community (PBC) and benthic bacterial community (BBC) are important for biogeochemical processes in freshwater lakes. Despite their ecological significance, little is known about their seasonal co-occurrence patterns and the ecological processes that drive them. In this study, we aimed to investigate the ecological associations among bacterial taxa and assembly processes of PBC and BBC in different seasons. We used 16S rRNA gene high-throughput sequencing of a total of 150 water and sediment samples collected from multiple lakes distributed in an urban region of China during winter and summer. Our results revealed that PBC showed stronger seasonal variations in co-occurrence patterns than BBC, suggesting that BBC had greater temporal stability than PBC. Winter PBC network was characterized by higher connectivity and complexity, and thereby the formation of a highly stable community structure; whereas lower connectivity arising from the presence of fewer predicted keystone taxa (hubs and connectors in a network) was destabilizing to summer PBC network. In addition, the phylum Firmicutes identified as a putative keystone taxon of PBC in both seasons played a non-negligible role in maintaining network structure which may result from strong functional associations with other bacterioplankton. Temperature and pH were the best explanatory factors predicting the seasonal co-occurrence patterns of PBC and BBC, respectively. Normalized stochasticity ratio based on null-model analysis indicated that deterministic processes overwhelmed stochastic processes in governing the assembly of PBC and BBC in both seasons. However, we observed a greater influence of ecological stochasticity on BBC assembly than PBC assembly in both seasons. Taken together, these findings provide insights into understanding the impacts of habitat heterogeneity and seasonal variability on microbial assemblage patterns in lake ecosystems.

miR-150 inhibitor ameliorates adriamycin-induced focal segmental glomerulosclerosis.

Focal segmental glomerulosclerosis (FSGS) is the most common cause of adult nephrotic syndrome in USA. Its mechanisms remain unclear and the effective treatment lacks. We previously reported that upregulation of microRNA (miR)-150 in human podocytes increases profibrotic proteins and decreases anti-fibrotic suppressor of cytokine signaling 1 (SOCS1). We aimed to clarify whether miR-150 inhibitor can ameliorate glomerular injury and to identify its corresponding mechanisms in adriamycin-induced FSGS mice. We found that renal miR-150 increased in adriamycin-induced FSGS mice and FAM-labeled locked nucleic acid-anti-miR-150 (LNA-anti-miR-150) was absorbed by the animal kidneys 6 h after subcutaneous injection. The administration of LNA-anti-miR-150 (2 mg/kg BW twice weekly for 6 w) inhibited renal miR-150 levels without systemic toxicity. With renal miR-150 inhibition, proteinuria, hypoalbuminemia, and hyperlipemia were ameliorated in FSGS mice compared to the scrambled LNA. Meanwhile, the elevated profibrotic proteins and proinflammatory cytokines, decreased antifibrotic SOCS1, and the filtration of T cells in FSGS mice were reverted by LNA-anti-miR-150. Finally, we found that miR-150 most located on podocytes in renal biopsies of FSGS patients. We conclude that LNA-anti-miR-150 might be a novel promising therapeutic agent for FSGS. The renal protective mechanisms might be mediated by anti-fibrosis and anti-inflammation as well as reducing infiltration of T cells in the kidney.

LNA-anti-miR-150 ameliorated kidney injury of lupus nephritis by inhibiting renal fibrosis and macrophage infiltration.

BACKGROUND: The prevalence of lupus nephritis (LN) remains high despite various emerging monoclonal antibodies against with targeting systemic lupus erythematosus (SLE). Renal fibrosis is the main feature of late stage LN, and novel therapeutic agents are still needed. We previously reported that microRNA (miR)-150 increases in renal biopsies of American LN patients and that miR-150 agonist promotes fibrosis in cultured kidney cells. Presently, we aim to verify whether locked nucleic acid (LNA)-anti-miR-150 can ameliorate LN in mice and to investigate its corresponding mechanisms. METHODS: We first observed natural history and renal miR-150 expression in female Fcgr2b-/- mice of a spontaneously developed LN model. We then verified miR-150 renal absorption and determined the dose of the suppressed miR-150 by subcutaneous injection of LNA-anti-miR-150 (2 and 4 mg/kg). Thirdly, we investigated the therapeutic effects of LNA-anti-miR-150 (2 mg/kg for 8 weeks) on LN mice and the corresponding mechanisms by studying fibrosis-related genes, cytokines, and kidney resident macrophages. Lastly, we detected the expression of renal miR-150 and the mechanism-associated factors in renal biopsies from new onset untreated LN patients. RESULTS: Fcgr2b-/- mice developed SLE indicated by positive serum autoantibodies at age 19 weeks and LN demonstrated by proteinuria at age 32 weeks. Renal miR-150 was overexpressed in LN mice compared to wild type mice. FAM-labeled LNA-anti-miR-150 was absorbed by both glomeruli and renal tubules. LNA-anti-miR-150 suppressed the elevated renal miR-150 levels in LN mice compared to the scrambled LNA without systemic toxicity. Meanwhile, serum double strand-DNA antibody, proteinuria, and kidney injury were ameliorated. Importantly, the elevated renal pro-fibrotic genes (transforming growth factor-ß1, α-smooth muscle antibody, and fibronectin) and decreased anti-fibrotic gene suppressor of cytokine signal 1 were both reversed. Renal pro-inflammatory cytokines (interferon-γ, interleukin-6, and tumor necrosis factor-α) and macrophages were also decreased. In addition, the changes of renal miR-150 and associated proteins shown in LN mice were also seen in human subjects. CONCLUSIONS: LNA-anti-miR-150 may be a promising novel therapeutic agent for LN in addition to the current emerging monoclonal antibodies, and its renal protective mechanism may be mediated by anti-fibrosis and anti-inflammation as well as reduction of the infiltrated kidney resident macrophages.

Variations of bacterial community during the decomposition of Microcystis under different temperatures and biomass.

BACKGROUND: The decomposition of Microcystis can dramatically change the physicochemical properties of freshwater ecosystems. Bacteria play an important role in decomposing organic matters and accelerating the cycling of materials within freshwater lakes. However, actions of the bacterial community are greatly influenced by temperature and the amount of organic matter available to decompose during a bloom. Therefore, it is vital to understand how different temperatures and biomass levels affect the bacterial community during the decomposition of Microcystis. RESULTS: Microcystis addition reduced the diversity of bacterial community. The composition of bacterial community differed markedly between samples with different biomass of Microcystis (no addition, low biomass addition: 0.17 g/L, and high biomass addition: 0.33 g/L). In contrast, temperature factor did not contribute much to the different bacterial community composition. Total nitrogen (TN), total phosphorus (TP), total organic carbon (TOC), ammonia nitrogen (NH4+-N) and oxidation-reduction potential (ORP) were the key measured environmental variables shaping the composition of bacterial community. CONCLUSIONS: Decomposition of Microcystis changed the physicochemical characteristics of the water and controlled the diversity and composition of the bacterial community. Microcystis biomass rather than temperature was the dominant factor affecting the diversity and composition of the bacterial community.

Seasonality overwhelms aquacultural activity in determining the composition and assembly of the bacterial community in Lake Taihu, China.

Aquaculture accounts for an extremely valuable and rapidly expanding sector of global food production, yet its environmental impacts on aquatic ecosystems have attracted much concern. In this study, we collected water samples from eastern Lake Taihu, China. We targeted sites varying in their intensity of aquacultural activities and sampled them over multiple seasons. For each sample, we measured physicochemical variables, and we sequenced the 16S rRNA gene of the respective bacterial communities using an Illumina second-generation sequencing platform. Marked differences in diversity and bacterial community composition were observed between seasons, whereas we observed relatively weak differences between sites. Remarkable differences in the abundance of the bacterial community were observed at the phylum and genus levels across the different seasons. Stochastic processes dominated the assembly of bacterial communities in the aquaculture-influenced systems, and the assembly processes of bacterial community differed between seasons. Our observations highlight the effect of seasonality on bacterial communities and provide a more complete knowledge base for the proper assessment of the effects of aquacultural activities on freshwater ecosystems.

Clinical significance and expression of serum Golgi protein 73 in primary hepatocellular carcinoma.

BACKGROUND: Golgi protein 73 (GP73) is a potential serum marker for the diagnosis of hepatocellular carcinoma (HCC). However, the diagnostic value of GP73 for HCC remains controversy, and little is known about the relationship between serum GP73 concentration and clinical characteristics of HCC. This study was designed to analyze the clinical values of GP73 in diagnosing HCC and the relationship between GP73 level and clinical characteristics in HCC patients. MATERIALS AND METHODS: In this study, a total of 443 serum samples including 180 patients with HCC, 61 patients with liver cirrhosis (LC), 99 chronic hepatitis patients, and 103 healthy individuals were enrolled from November 2011 to April 2013. Enzyme-linked immunosorbent assay and chemiluminescent immunoassay were used to detect the serum level of GP73 and other biomarkers. RESULTS: GP73 level in HCC group was significantly higher than LC group, chronic hepatitis B group, and healthy control group. In HCC group, GP73 level significantly increased in patients with lymphatic metastasis; moreover, GP73 level in Child-Pugh Class B and C groups was statistically significantly higher than that in Child-Pugh Class A group (P < 0.05). The area under the receiver operating characteristic (AUROC) curve of GP73 and alpha-fetoprotein (AFP) was 0.840 and 0.718, respectively, when diagnosing HCC. Moreover, the AUROC curve by use of the combination of GP73 and AFP was 0.903. The differences among these three aspects were statistically significant (P < 0.05). CONCLUSION: GP73 was better than AFP for the diagnosis of HCC, and the expression of serum GP73 is related with the clinical characteristics of HCC patients.