(+)- and (-)-Tedanine, a pair of new enantiomeric indolone alkaloids from the marine sponge Tedania sp.

(+)- and (-)-Tedanine [(+)-1 and (-)-1], a pair of new enantiomeric indolone alkaloids, along with nine compounds (2-10) were isolated from the marine sponge Tedania sp. The structures of (+)-1 and (-)-1 including absolute configurations were determined by spectroscopic analysis and quantum chemical calculation. Compounds (+)-1 and (-)-1 were the first examples of indolone alkaloids isolated from this genus. In addition, the cytotoxic and antibacterial activities of these compounds were also evaluated.

Analysis of risk factors for abdominal aortic calcification in dialysis patients and its influence on long-term recovery.

This study investigated the risk factors of abdominal aortic calcification (AAC) in patients with stage 5 chronic kidney disease (CKD) and the effects of AAC and different dialysis methods on the 3-year survival rate of patients with stage 5 CKD. A retrospective cohort study was conducted on stage 5 CKD patients who received dialysis treatment. The general data were collected, and all fasting venous blood samples were harvested before the first dialysis to detect biochemical markers. The AAC was evaluated by lateral abdominal X-ray. The patients were followed up with a cut-off date of March 31, 2022, with all-cause mortality as the endpoint event. A total of 205 patients were included. multivariable Cox regression analysis confirmed that AAC (hazard ratio (HR) = 2.173, 95% CI 1.029-4.588, p = 0.042), advanced age (HR = 1.061, 95% CI 1.031-1.093, p < 0.001), duration of dialysis (HR = 1.015, 95% CI 1.007-1.032, p < 0.001), diabetes (HR = 3.966, 95% CI 2.164-7.269, p < 0.001), and hypertension (HR = 1.897, 95% CI 1.089-3.303, p = 0.024) were independent risk factors for 3-year mortality. However, peritoneal dialysis (HR = 0.366, 95% CI 0.165-0.812, p = 0.013), high albumin (HR = 0.882, 95% CI 0.819-0.950, p = 0.001), and high hemoglobin (HR = 0.969, 95% CI 0.942-0.997, p = 0.031) were protective factors for 3-year mortality in stage 5 CKD patients. Increased age, long-term dialysis, high level of intact parathyroid hormone, diabetes, and hypertension are closely related to the occurrence of AAC in patients with stage 5 CKD. In addition, AAC is an independent risk factor for all-cause mortality in patients with stage 5 CKD.

Key role of •O2- in promoting deep degradation of VOCs in VUV-based process.

VUV photolysis presents a simple process for VOCs degradation, while the poor mineralization rate and extensive by-products greatly limit its application. In this study, the contribution and synergy between •OH and •O2- to toluene degradation in the VUV-based process were comprehensively investigated by controlling water and oxygen in the gas flow. It was found that •OH promoted the initial degradation of toluene and macromolecular intermediates, while •O2- dominated toluene mineralization by boosting the formation of small molecules and CO2. Compared with the •OH-dominated VUV photolysis, the presence of catalyst greatly changed the degradation pathway, promoted toluene mineralization into CO2 and reduced health toxicity via promoting •O2- formation. This study originally focuses on the key role of •O2- in VOCs deep oxidation and provides an effective strategy to boost its clean mineralization via the VUV-based process.

Enhanced methane production from the anaerobic co-digestion of food waste plus fruit and vegetable waste.

Food waste (FW) and fruit, vegetable waste (FVW) are important components of municipal solid waste, yet the performance and related mechanisms of anaerobic co-digestion of FW and FVW for methane production have been rarely investigated. In order to get a deeper understanding of the mechanisms involved, the mesophilic FW and FVW anaerobic co-digestion in different proportions was investigated. The experimental results showed that when the ratio of FW and FVW was 1/1 (in terms of volatile suspended solid), the maximum biomethane yield of 269.9 mL/g TCOD from the codigested substrate is significantly higher than that in FW or FVW anaerobic digestion alone. FW and FVW co-digestion promoted the dissolution and biotransformation of organic matter. When the recommended mixing ratio was applied, the maximum concentration of dissolved chemical oxygen demand (COD) was high as 11971 mg/L. FW and FVW co-digestion reduced the accumulation of volatile fatty acids (VFA) in the digestive system, thus reducing its negative impact on the methanogenesis process. FW and FVW co-digestion process synergistically enhanced microbial activity. The analysis of microbial population structure showed that when FW and FVW were co-digested at the recommended ratio, the relative abundance of Proteiniphilum increased to 26.5%, and the relative abundances of Methanosaeta and Candidatus Methanofastidiosum were also significantly increased. The results of this work provide a certain amount of theoretical basis and technical support for the co-digestion of FW and FVW.

A new chlorobenzoate derivative from the red alga Solieria sp.

A new chlorobenzoate derivative, solieriate (1), together with six known compounds (2-7), were isolated from the red alga Solieria sp. The structures of 1-7 were determined by comprehensive spectroscopic methods and X-ray diffraction analysis. Compound 1 is the first example of halogenated derivative isolated from this genus. In addition, 1 exhibited moderate antibacterial activity on A. baumannii with MIC value of 64 µg/ml.

Impacts of hydraulic conditions on microplastics biofilm development, shear stresses distribution, and microbial community structures in drinking water distribution pipes.

Both microplastic and biofilm are contamination sources in drinking water, but their integrated impacts on water quality have been rarely studied, especially in drinking water distribution pipes with complex hydraulic conditions. This study explored the impacts of hydraulic conditions (0-2 m/s) on microplastic biofilm (MP-BM) development, shear stresses distribution, and microbial community structures. The research was conducted for two weeks using a pilot test device to simulate practical water pipes. The following were the primary conclusions: (1) According to morphology analysis, clusters (>5 µm) significantly increased in the plastisphere when the flow velocity ranged from 0.55 m/s to 0.95 m/s, and average size of clusters decreased when the flow velocity ranged from 1.14 m/s to 1.40 m/s (2) Characteristics of MP-BM impact shear stress on both plastisphere and pipe wall biofilm. Shear stresses were positively correlated with flow velocity, number of MP-BM, and size of MP-BM, while negatively correlated with diameters of pipes. (3) 31 genera changed strictly and monotonously with the fluid velocity, accounting for 15.42%. Opportunistic pathogens in MP-BM such as Sediminibacterium, Curvibacter, and Flavobacterium were more sensitive to hydraulic conditions. Moreover, microplastics (<100 µm) deserve more attention to avoid human ingestion and to prevent mechanical damage and bio-chemical risks.

Interactive impacts of microplastics and chlorine on biological stability and microbial community formation in stagnant water.

Possibility of human exposure to microplastics (MPs) in water environment has been escalating, and subsequent challenges of MPs to biostability and biosafety in drinking water deserve more attention, especially in stagnant water. The present study explored the integrated impacts of MPs and chlorine on disinfection kinetics, microbial growth, and microbial community formation in drinking water, by setting MPs or microplastic-biofilm (MP-BM) under different disinfection conditions. The following were the primary conclusions: (1) The presence of MP and MP-BM led to the deterioration of water indices (especially turbidity) when chlorine was less than 1 mg/L. (2) MP/MP-BM accelerated the decay of disinfectants and MP-BM consumed more rapidly. Meanwhile, chlorine contributed to the level of BRP, ranging from 4.78 × 105 CFU/mL to 1.42 × 107 CFU/mL. (3) MP/MP-BM and chlorine integrally shaped microbial communities in water samples and biofilm samples. Microbial dissimilarity between isolated and hybrid MP-BM indicated manners of microbial field or non-contact communication. Microbial abundance and OPs were effectively controlled when chlorine was over 1 mg/L. (4) According to time-lag differential equations simulation, impulsive chlorination contributed to controlling microbial risks and DBPs induced by MP/MP-BM and water stagnation.

Producing and storing self-sustaining drinking water from rainwater for emergency response on isolated island.

Drinking water on isolated islands includes treated rainwater, water shipped from the mainland, and desalinated seawater. However, marine transportation and desalination plants are vulnerable to emergencies, such as extreme weather, making self-sustaining stand-by water for emergency response essential. Rainwater is ideal for producing the stand-by water, and rainwater harvesting is sustainable and clean, and prolonged biostability can be ensured by managing biological and chemical parameters. The present study applied a stand-by drinking water purification system (primarily including nanofiltration and low-dose chlorination) to explore the feasibility of producing and storing cleaner drinking water from rainwater and the following conclusions were drawn. First, treatment of rainwaters ensures biosafety for seven days, which is longer than that for untreated rainwater; the proportion of opportunistic pathogens decreased from 23.40-7.77% after nanofiltration, and it was proposed that the microbial community converges after advanced water treatment. Second, chemical qualities were improved. Local resource coral sand prevents pH in rainwater from decreasing below 6.5, and treated rainwater had lower disinfection by-product potential and higher disinfection efficiency, allowing periodical rainwater recycling. Third, harvesting rainwater was extremely cost-effective, with an operation cost of 1.5-2.5 RMB/m3. From biosafety, chemical safety, and economic cost perspectives, self-sustaining water from rainwater can contributes to the development of sustainable and cost-effective water supply systems on isolated islands. Mixing treated rainwater and desalinated seawater reasonably guarantees sufficiency and safety.

Overexpression of DJ-1 alleviates autosomal dominant polycystic kidney disease by regulating cell proliferation, apoptosis, and mitochondrial metabolism in vitro and in vivo.

BACKGROUND: DJ-1 is critical for the mitochondrial function associated with autosomal dominant polycystic kidney disease (ADPKD). We aimed to investigate DJ-1's function in the pathogenesis of ADPKD. METHODS: DJ-1 was knocked-down in IMCD3 cells to evaluate the effects of DJ-1 on cell phenotype and mitochondrial function in vitro. Furthermore, we generated three groups of mice with different expression levels of DJ-1 within an established ADPKD model: ADPKD, ADPKDpcDNA, and ADPKDpcDNA-DJ-1. RESULTS: DJ-1 knock-down significantly increased oxidative stress as well as the proliferation and apoptosis rate of IMCD3 cells, along with Bcl-2 down-regulation and the up-regulation of Ki67, PCNA, Bax, cleaved caspase-3, and cleaved caspase-9. DJ-1 knock-down suppressed the cellular respiration, Ca2+ absorption, and mitochondrial complex I activity in mitochondria. In vivo, we verified that DJ-1 was down-regulated in ADPKD models, and its overexpression attenuated the renal dysfunction in ADPKD models. The transgenic mice had a significantly smaller renal cyst and less interstitial fibrosis than control, accompanied byα-SMA, fibronectin, and TGF-ß1 up-regulation. Moreover, in vivo results confirmed DJ-1 overexpression inhibited the proliferation and apoptosis of tubular epithelial cells along with down-regulation of Ki67, PCNA, p53, intracellular Cyt c, cleaved caspase-3, and cleaved caspase-9 and the up-regulation of Bcl-2. CONCLUSIONS: DJ-1 was down-regulated in ADPKD models, and its overexpression may attenuate the renal dysfunction and pathological damage by regulating the proliferation, apoptosis, oxidative stress and mitochondrial metabolism, which may be mediated by the p53 signaling pathway.

Mitochondrial TRPC3 promotes cell proliferation by regulating the mitochondrial calcium and metabolism in renal polycystin-2 knockdown cells.

PURPOSE: Previous studies indicate that autosomal dominant polycystic kidney disease (ADPKD) cells exhibited dysregulated calcium homeostasis and enhanced cell proliferation. TRPC3 has been shown to function in the modulation of calcium and sodium entry, but whether TRPC3 plays a role in cellular abnormalities of ADPKD cells has not been defined. METHODS: Human conditionally immortalized proximal tubular epithelial cells and mouse IMCD3 cells were used with polycystin-2 (PC2, TRPP2) knockdown. Cell proliferation assay was used to detect the cell proliferations upon different treatments. QRT-PCR and western blotting were used to measure the expression profiles of TRPP2 and other proteins. High-resolution respirometry, enzymic activities and ROS levels were detected to reflect the mitochondrial functions. Calcium and sodium uptakes were measured using Fura2-AM and SBFI dyes. RESULTS: We showed that PC2 knockdown promoted cell proliferation, ROS productions and ERK phosphorylation, compared with negative control. Meanwhile, we demonstrated that receptor-operated calcium entry (ROCE) exhibited less reductions compared with store-operated calcium entry (SOCE) upon PC2 knockdown. Inhibition of ROCE and SOCE by specific inhibitors partially reversed the enhanced cell proliferation, ROS productions and ERK phosphorylation induced by PC2 knockdown. Moreover, TRPC3 upregulation was observed upon PC2 knockdown, which acted as both SOC and ROC, promoting cation entry, cell proliferation and ERK phosphorylation. Furthermore, we showed that mitochondrial located TRPC3 was upregulated and modulating mitochondrial calcium uptake, thus promoting the ROS productions in the presence of PC2 knockdown. CONCLUSIONS: We demonstrated that TRPC3 upregulation upon PC2 knockdown aggravated the mitochondrial abnormalities and cell proliferation by modulating mitochondrial calcium uptake. Targeting TRPC3 might be a promising target for ADPKD treatment.

The combination of metformin and 2-deoxyglucose significantly inhibits cyst formation in miniature pigs with polycystic kidney disease.

BACKGROUND AND PURPOSE: The pathogenic mechanism of autosomal dominant polycystic kidney disease (ADPKD) is unclear. Similar to tumour cells, polycystic kidney cells are primarily dependent on aerobic glycolysis for ATP production. Compared with rodents, miniature pigs are more similar to humans. This study is the first time to investigate the effects of the combination of metformin and 2-deoxyglucose (2DG) in a pig model of chronic progressive ADPKD. EXPERIMENTAL APPROACH: A miniature pig ADPKD model was established by inducible deletion of the PKD1 gene. Blood, urine and kidney biopsy specimens were collected for analysis at specific times. The renal vesicle index was analysed by three-dimensional reconstruction of CT scans. Markers of the mammalian target of rapamycin (mTOR) and ERK signalling pathways and associated metabolism were detected by Western blots and colorimetry. KEY RESULTS: The three-dimensional reconstruction of CT scans indicated a markedly lower renal vesicle index in the combination therapy group. Each drug intervention group showed a significantly lower serum creatinine and urinary protein/creatinine ratio. This treatment regimen also inhibited the activities of markers of the proliferation-related mTOR and ERK pathways, and the expression of key enzymes involved in glycolysis, as well as reducing the production of ATP and lactic acid. CONCLUSIONS AND IMPLICATIONS: This study showed that the combination of metformin and 2DG blocked the formation of renal cysts and improved the renal function in ADPKD miniature pigs. Our results indicate that the combination of metformin and 2DG may be a promising therapeutic strategy in human ADPKD.

The changes in glucose metabolism and cell proliferation in the kidneys of polycystic kidney disease mini-pig models.

The pathogenic mechanism of polycystic kidney disease (PKD) is unclear. Abnormal glucose metabolism is maybe involved in hyper-proliferation of renal cyst epithelial cells. Mini-pigs are more similar to humans than rodents and therefore, are an ideal large animal model. In this study, for the first time, we systematically investigated the changes in glucose metabolism and cell proliferation signaling pathways in the kidney tissues of chronic progressive PKD mini-pig models created by knock-outing PKD1gene. The results showed that in the kidneys of PKD mini-pigs, the glycolysis is increased and the expressions of key oxidative phosphorylation enzymes Complexes I and IV significantly decreased. The activities of mitochondrial respiration chain Complexes I and IV significantly decreased; the phosphorylation level of key metabolism-modulating molecule AMP-activated protein kinase (AMPK) significantly decreased; and the mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK) signaling pathway are activated obviously. This study showed that in the kidneys of PKD mini-pigs, the level of glycolysis significantly increased, oxidative phosphorylation significantly decreased, and cell proliferation signaling pathways significantly activated, suggesting that metabolic changes in PKD may result in the occurrence and development of PKD through the activation of proliferation signaling pathways.