Una ingesta explosiva / An explosive intake

La ingesta de petardo supone un riesgo potencial para la vida del paciente si este contiene el compuesto tóxico denominado fósforo amarillo (FA). Afortunadamente, dicho material no es utilizado actualmente en nuestro país para la fabricación de productos de pirotecnia, no siendo así en otras regiones del mundo como Asia o América Latina. La ingesta de FA puede causar el fallecimiento del paciente hasta en un 20-50% de los casos por acumulación tóxica en el organismo, produciendo fundamentalmente fallo hepático y, consecuentemente, fallo multiorgánico. Los petardos en España contienen materiales no tóxicos para el organismo, por lo que su ingesta puede producir náuseas y molestias abdominales, pero no un riesgo letal para el paciente. (AU)

The ingestion of firecrackers poses a potential risk to the patient's life if they contain the toxic component called yellow phosphorus (YFP). Fortunately, this material is not currently used in our country for the manufacture of pyrotechnic products, but this is not the case in other regions of the world such as Asia or Latin America. The ingestion of YFP can cause the death of up to 20-50% of cases, by toxic accumulation in the organism, producing mainly hepatic failure and consequently multiorgan failure. Firecrackers in Spain contain non-toxic materials for the organism, so their ingestion may cause nausea and abdominal discomfort, but not a lethal risk for the patient. (AU)

A historical review of 'phossy jaw'.

The aim of this article is to stimulate interest and discussion on the pathogenesis of 'phossy jaw'. Historical evidence from newspapers and articles of the time is presented, as other scientific evidence is largely absent. It has stimulated considerable interest in present-day media due to the struggles of nineteenth century reformers to improve working conditions against an apathetic government and weak enforcement of regulation. Those afflicted were often young women who suffered severe pain, loss of segments of jaw, and disfigurement.

Identification of Phosphorus Stress Related Proteins in the Seedlings of Dongxiang Wild Rice (Oryza Rufipogon Griff.) Using Label-Free Quantitative Proteomic Analysis.

Phosphorus (P) deficiency tolerance in rice is a complex character controlled by polygenes. Through proteomics analysis, we could find more low P tolerance related proteins in unique P-deficiency tolerance germplasm Dongxiang wild rice (Oryza Rufipogon, DXWR), which will provide the basis for the research of its regulation mechanism. In this study, a proteomic approach as well as joint analysis with transcriptome data were conducted to identify potential unique low P response genes in DXWR during seedlings. The results showed that 3589 significant differential accumulation proteins were identified between the low P and the normal P treated root samples of DXWR. The degree of change was more than 1.5 times, including 60 up-regulated and 15 downregulated proteins, 24 of which also detected expression changes of more than 1.5-fold in the transcriptome data. Through quantitative trait locus (QTLs) matching analysis, seven genes corresponding to the significantly different expression proteins identified in this study were found to be uncharacterized and distributed in the QTLs interval related to low P tolerance, two of which (LOC_Os12g09620 and LOC_Os03g40670) were detected at both transcriptome and proteome levels. Based on the comprehensive analysis, it was found that DXWR could increase the expression of purple acid phosphatases (PAPs), membrane location of P transporters (PTs), rhizosphere area, and alternative splicing, and it could decrease reactive oxygen species (ROS) activity to deal with low P stress. This study would provide some useful insights in cloning the P-deficiency tolerance genes from wild rice, as well as elucidating the molecular mechanism of low P resistance in DXWR.

Black Phosphorus Nanosheet Encapsulated by Zeolitic Imidazole Framework-8 for Tumor Multimodal Treatments.

Black phosphorus (BP) nanosheet is easily oxidized by oxygen and water under ambient environment, thus, reliable BP passivation techniques for biomedical applications is urgently needed. A simple and applicable passivation strategy for biomedical applications was established by encapsulating BP nanosheet into zeolitic imidazole framework-8 (ZIF-8). The resulted BP nanosheet in ZIF-8 (BP@ZIF-8) shows not only satisfied chemical stability in both water and phosphate buffered saline (PBS), but also excellent biocompatibility. Notably, BP nanosheet endows the prepared BP@ZIF-8 with prominent photothermal conversion efficiency (31.90%). Besides passivation BP, ZIF-8 provides the BP@ZIF-8 with high drug loading amount (1353.3 mg g-1). Moreover, the loaded drug can be controlled release by pH stimuli. Both in vitro and in vivo researches verified the resulted BP@ZIF-8 an ideal candidate for tumor multimodal treatments.

Bone mesenchymal stem cell derived exosomes alleviate high phosphorus-induced calcification of vascular smooth muscle cells through the NONHSAT 084969.2/NF-κB axis.

Our previous study showed that bone marrow mesenchymal stem cell derived exosomes (BMSC-Exos) suppress high phosphorus (Pi)-induced calcification of vascular smooth muscle cells (VSMCs). However, the mechanism had remained unclear. This study aimed to investigate the mechanism by which BMSC-Exos inhibit vascular calcification (VC). We found that BMSC-Exos reduced high Pi-induced Runx2, osteocalcin and BMP2 expression and inhibited the calcium deposition. Gene expression of human VSMCs stimulated by Pi or Pi plus BMSC-Exos (Pi + Exo) was systematically examined by microarray technology. NONHSAT 084969.2 and transcription factor p65 expression was significantly lower in the Pi + Exo group compared with the Pi group. This finding indicated that NONHSAT 084969.2 and the nuclear factor-κB pathway might play an important role in VC inhibition by BMSC-Exos. By silencing NONHSAT 084969.2 with small interfering RNA, Runx2, BMP2, and osteocalcin expression was decreased significantly. The calcified nodule content and alkaline phosphatase activity were reduced after NONHSAT 084969.2 inhibition and p65, p50, and IκB kinase-α expression was decreased significantly. These results indicated that BMSC-Exos inhibited Pi-induced transdifferentiation and calcification of VSMCs by regulating the NONHSAT 084969.2/nuclear factor-κB axis.

Investigation into the trophic transfer and acute toxicity of phosphorus-based nano-agromaterials in Caenorhabditis elegans.

Biogenic phosphorus (P) based - nanomaterials (NMs) are currently being explored as nanofertilizers. In this study, the acute toxic effects and trophic transfer of multiple types of P-based NMs were examined on soil-dwelling nematode, Caenorhabditis elegans. The study involved four variants of nanohydroxyapatites (nHAPs) synthesized either via a biogenic or a chemical route and another NM, nanophosphorus (nP), biosynthesized from bulk rock phosphate (RP). The pristine NMs differed in their physicochemical properties with each possessing different shapes (biogenic nHAP: platelet-shaped, ˜35 nm; biogenic nP, ˜5-10 nm: dots; chemically synthesized nHAPs: spherical, ˜33 nm, rod, ˜80 nm and needle-shaped, ˜64 nm). The toxic effects of NMs' in C. elegans were assessed using survival, hatching and reproductive cycle as the key endpoints in comparison to bulk controls, calcium phosphate and RP. The interactions and potential uptake of fluorescent-tagged nHAP to E. coli OP50 and C. elegans were investigated using confocal microscopy. The transformation of NMs within the nematode gut was also explored using dynamic light scattering and electron microscopy. C. elegans exposed to all of the variants of nHAP and the nP had 88-100% survival and 82-100% hatch rates and insignificant effects on brood size as observed at the tested environmentally relevant concentrations ranging from 5 to 100 µg.mL-1. Confocal microscopy confirmed the interaction and binding of fluorescent-tagged nHAP with the surface of E. coli OP50 and their trophic transfer and internalization into C. elegans. Interestingly, there was only a small reduction in the hydrodynamic diameter of the nHAP after their uptake into C. elegans and the transformed NMs did not induce any additional toxicity as evident by healthy brood sizes after 72 h. This study provides key information about the environmental safety of agriculturally relevant P-based NMs on non-target species.

Cytotoxicity of black phosphorus quantum dots on lung-derived cells and the underlying mechanisms.

Black phosphorus quantum dots (BP-QDs) are a new type of zero-dimensional (0D) nanomaterial that has been widely used due of their superior properties in many biomedical fields, but limited studies have focused on the biocompatibility of BP-QDs, particularly in the respiratory system. In this study, we investigated the potential lung cell toxicity of BP-QDs in vitro. Two human lung-derived cells, A549 and Beas-2B, were treated with 5∼20 µg/mL BP-QDs for 24 h. The results showed that BP-QDs triggered significant lung cell toxicity, including a dose-dependent decrease in cell viability, lactate dehydrogenase (LDH) leakage, cell shape changes, cellular oxidative stress and cell cycle arrest. In addition, pretreatment with the classical phagocytosis inhibitor cytochalasin D (Cyto D) alleviated the decrease in cell viability and LDH leakage induced by BP-QDs. In contrast, BP-QDs induced the production of cellular reactive oxygen species (ROS) and decreases in the glutathione level, whereas the ROS scavenger N-acetyl-L-cysteine (NAC) could protect A549 and Beas-2B cells from BP-QD-induced cellular oxidative stress. Taken together, the results from this study indicate that the potential toxic effects and mechanisms of BP-QDs in two different human lung cells should be considered to evaluate the lung cell safety of BP-QDs.

Lack of Endothelial Nitric Oxide Synthase Accelerates Ectopic Calcification in Uremic Mice Fed an Adenine and High Phosphorus Diet.

Ectopic calcification is a risk of cardiovascular disease in chronic kidney disease (CKD) patients, and impaired endothelial nitric oxide synthase (eNOS) is involved in the CKD complications. However, whether eNOS dysfunction is a cause of ectopic calcification in CKD remains to be elucidated. To address this issue, we investigated the role of eNOS in ectopic calcification in mice with renal injury caused by an adenine and high-phosphorus (Ade + HP) diet. DBA/2J mice, a calcification-sensitive strain, were fed Ade + HP for 3 weeks. Expression levels of eNOS-related genes were reduced significantly in their calcified aorta. C57BL/6J is a calcification-resistant strain, and wild-type mice showed mild calcified lesions in the aorta and kidney when given an Ade + HP diet for 4 weeks. In contrast, a lack of eNOS led to the development of severe aortic calcification accompanied by an increase in runt-related transcription factor 2, an osteochondrogenic marker. Increased renal calcium deposition and the tubular injury score were remarkable in mice lacking eNOS-fed Ade + HP. Exacerbation of ectopic calcification by a lack of eNOS is associated with increased oxidative stress markers such as nicotinamide adenine dinucleotide phosphate oxidases. In conclusion, eNOS is critically important in preventing ectopic calcification. Therefore, the maintenance of eNOS is useful to reduce cardiovascular disease events and to improve prognosis in CKD patients.

Effects of aging and transformation of anatase and rutile TiO2 nanoparticles on biological phosphorus removal in sequencing batch reactors and related toxic mechanisms.

The effect of nanomaterials aging, namely the transformation of comprehensive characteristics after experiencing real or complex environmental behaviors, on their ecotoxicology is still lacking. Moreover, the mechanisms by which NPs influence biological phosphorus (P) removal during sewage treatment require further elucidation. Therefore, we used both pristine and aged anatase (TiO2-A) and rutile (TiO2-R) NPs to investigate the mechanisms by which NPs affect P removal in a SBR. At 0.1 mg/L, the four types of NPs (pristine and aged) had no significant effect on sludge purification after acute (72-h) exposure under simulated sunlight. However, at 50 mg/L-regardless of the crystalline phase of the NPs-SOP and COD removal efficiency dropped steeply to approximately 42.2-82.4 % (p < 0.05) and 69.8-83.3 % (p < 0.05), respectively, especially in the pristine TiO2-NPs groups because of decrease of richness and diversity of genus level of PAOs and enzyme activity of both PPK and PPX, and the sluggish transformation of PHA and glycogen. Aging reduced the ability of NPs toxicity. The toxicity mechanisms of TiO2-NPs included lipid peroxidation and contact damage, or leakage from bacterial cytoplasmic membrane, which are closely related to photooxidation capacity and aqueous solution stability-i.e., nanoscale effects-and the impacts of aging or inclusion.

N, P-co-doped carbon dots as a dual-mode colorimetric/ratiometric fluorescent sensor for formaldehyde and cell imaging via an aminal reaction-induced aggregation process.

Novel colorimetric and ratiometric fluorometric dual-mode N, P-co-doped carbon nanodots, BPEI-CDs, for highly sensitive and selective detection of formaldehyde (FA) were successfully prepared from N-(phosphonomethyl)iminodiacetic acid (PMIDA) and branched polyethyleneimine (BPEI). The treatment of FA caused a remarkable linear enhancement of ratiometric fluorescence (F501 nm/F408 nm) in a wide range of 0-40 µM with a detection limit (LOD) of 0.47 µM (3σ/k), along with distinct color changes from colorless to light yellow. Mechanistic study shows that this electron-rich system, formed by the cooperative roles of N and P, promoted the FA-induced Schiff bases formation reaction, which contributed to the CD aggregation-induced emission (AIE) "turn-on" response and enhancement of π-conjugation-induced bathochromic behaviors. Furthermore, N, P-co-doped BPEI-CDs were successfully applied to the determination of FA in bean sprout samples. Using the standard addition method, the recoveries ranged from 96.9 to 101.8%, and the relative standard deviation (RSD) was in the range 2.23 to 3.21%. The application for intracellular FA sensing further verified that this novel nanoprobe may offer a new venue for the design of simple, low-cost, and sensitive biosensors. Graphical abstract.

Phosphorus toxicity disrupts Rubisco activation and reactive oxygen species defence systems by phytic acid accumulation in leaves.

Phosphorus (P) is an essential mineral nutrient for plants. Nevertheless, excessive P accumulation in leaf mesophyll cells causes necrotic symptoms in land plants; this phenomenon is termed P toxicity. However, the detailed mechanisms underlying P toxicity in plants have not yet been elucidated. This study aimed to investigate the molecular mechanism of P toxicity in rice. We found that under excessive inorganic P (Pi) application, Rubisco activation decreased and photosynthesis was inhibited, leading to lipid peroxidation. Although the defence systems against reactive oxygen species accumulation were activated under excessive Pi application conditions, the Cu/Zn-type superoxide dismutase activities were inhibited. A metabolic analysis revealed that excessive Pi application led to an increase in the cytosolic sugar phosphate concentration and the activation of phytic acid synthesis. These conditions induced mRNA expression of genes that are activated under metal-deficient conditions, although metals did accumulate. These results suggest that P toxicity is triggered by the attenuation of both photosynthesis and metal availability within cells mediated by phytic acid accumulation. Here, we discuss the whole phenomenon of P toxicity, beginning from the accumulation of Pi within cells to death in land plants.

Gold nanobipyramid-loaded black phosphorus nanosheets for plasmon-enhanced photodynamic and photothermal therapy of deep-seated orthotopic lung tumors.

Various types of photodynamic agents have been explored for photodynamic therapy (PDT) to destroy cancers located in deep tissues. However, these agents are generally limited by low singlet oxygen (1O2) yields owing to weak absorption in the optical transparent window of biological tissues. Accordingly, in this work, we developed a nanocomposite through the assembly of gold nanobipyramids (GNBPs) on black phosphorus nanosheets (BPNSs). This nanocomposite could simultaneously enhance 1O2 generation and hyperthermia by localized surface plasmon resonance in cancer therapy. As two-dimensional inorganic photosensitizers, BPNSs were hybridized with GNBPs to form BPNS-GNBP hybrid nanosheets. The hybridization markedly increased 1O2 production by the BPNSs through plasmon-enhanced light absorption. The nanocomposite exhibited a higher photothermal conversion efficiency than the BPNSs alone. In vitro and in vivo assays indicated that the BPNS-GNBP hybrid nanocomposite exhibited good tumor inhibition efficacy owing to simultaneous dual-modality phototherapy. In vivo, the nanocomposite suppressed deep-seated tumor growth with minimal adverse effects in mice bearing orthotopic A549 human lung tumors. Taken together, these results demonstrated that our BPNS-GNBP nanocomposite could function as a promising dual-modality phototherapeutic agent for enhanced cancer therapy in future cancer treatments. STATEMENT OF SIGNIFICANCE: In this study, we established a new nanocomposite by assembly of gold nanobipyramids (GNBPs) on black phosphorus nanosheets (BPNSs). Characterization of this nanocomposite showed that BPNS-GNBP enhanced 1O2 generation and hyperthermia. BPNS-GNBP exhibited good tumor inhibition efficacy in vivo and in vitro owing to simultaneous dual-modal phototherapy functions. Moreover, BPNS-GNBP suppressed deep-seated tumor growth in vivo and did not show adverse effects in mice bearing orthotopic A549 human lung tumors. Overall, these results showed that BPNS-GNBP may be used as a promising dual-modal phototherapeutic agent for enhanced cancer therapy in future clinical applications.

LVFFARK-PEG-Stabilized Black Phosphorus Nanosheets Potently Inhibit Amyloid-ß Fibrillogenesis.

Deposition of amyloid-ß (Aß) aggregates in the brain is a main pathological hallmark of Alzheimer's disease (AD), so inhibition of Aß aggregation has been considered as a promising strategy for AD prevention and treatment. Black phosphorus (BP) is a 2D nanomaterial with high biocompatibility and unique biodegradability, but its potential application in biomedicine suffers from the rapid degradability and unfunctionability. To overcome the drawbacks and broaden its application, we have herein designed an Aß inhibitor (LK7)-coupled and polyethylene glycol (PEG)-stabilized BP-based nanosystem. The PEGylated-LK7-BP nanosheets (PEG-LK7@BP) not only exhibited a good stability but also demonstrated a significantly enhanced inhibitory potency on Aß42 fibrillogenesis in comparison with its counterparts. This elaborately designed PEG-LK7@BP stopped the conformational transition and suppressed the fibrillization of Aß42, so it could completely rescue cultured cells from the toxicity of Aß42 (by increasing the cell viability from 72 to 100%) at 100 µg/mL. It is considered that PEG-LK7@BP could bind Aß species by enhanced electrostatic and hydrophobic interactions and thus efficiently alleviated Aß-Aß interactions. Meanwhile, the coupled LK7 on the BP surface formed a high local concentration that enhanced the affinity between the nanosystem and Aß species. Finally, PEG could improve the stability and dispersibility of the nanoplatform to make it show an increased inhibitory effect on the amyloid formation. Hence, this work proved that PEG-LK7@BP is a promising nanosystem for the development of amyloid inhibitors fighting against AD.

Directional extraction and penetration of phosphorene nanosheets to cell membranes.

Recently, phosphorene, a novel two-dimensional nanomaterial with a puckered surface morphology, was shown to exhibit cytotoxicity, but its underlying molecular mechanisms remain unknown. Herein, using large scale molecular dynamics simulations, we show that phosphorene nanosheets can penetrate into and extract large amounts of phospholipids from the cell membranes due to the strong dispersion interaction between phosphorene and lipid molecules, which would reduce cell viability. The extracted phospholipid molecules are aligned along the wrinkle direction of the phosphorene nanosheet because of its unique puckered structure. Our results also reveal that small phosphorene nanosheets penetrate into the cell membrane in a specific direction which is determined by the size and surface topography of phosphorene and the thickness of the membrane. These findings might shed light on understanding phosphorene's cytotoxicity and would be helpful for the future potential biomedical applications of phosphorene, such as biosensors and antibacterial agents.

In Vitro and In Vivo Toxicity of Black Phosphorus Nanosheets.

As a new kind of two-dimensional nanomaterial, black phosphorus (BP) nanosheets have attracted significant interests in diverse bioapplications due to their unique structure and physicochemical properties. Despite BP nanosheets' advantages in cancer diagnosis and therapy applications, their biosafety issues are still unclear. Herein, we report a systematic study on the In Vitro and In Vivo toxicity of BP nanosheets. In Vitro experiments showed that BP nanosheets decrease the viability of human bronchial epithelial cells in a time- and dose-dependent manner. The mechanism study showed that BP nanosheets interfere with mitochondrial membrane potential, leading to an increase in intracellular ROS. These responses further initiated the activation of the caspase-3 and ultimately dictated cells to undergo apoptosis. Then, the In Vivo experiments of BP nanosheets revealed that single injection of BP nanosheets does not cause toxicity to mice in a short period of time, whereas multiple injections of BP nanosheets exert adverse effects on liver and renal function of mice. Interestingly, the liver and renal function of the mice returned to normal after a recovery period. Our findings provide insights into the rational design of BP nanosheets and guide their applications in biomedical fields.

Antagonistic co-limitation through ion promiscuity - On the metal sensitivity of Thalassiosira oceanica under phosphorus stress.

Nutrient limitation of primary producers is a fundamental principle in biogeochemical oceanography and has been used with great success in prescribing understanding to patterns of marine primary productivity. In recent years the paradigm of nutrient limitation has expanded from single nutrient limitation towards concepts of co-limitation by multiple resources. Interactive effects between multiple limiting resources are now thought commonplace in marine microbial communities. Here we investigate the response exhibited by phosphate-limited Thalassiosira oceanica to elevated concentrations of the phosphate analogs vanadate, arsenate and molybdate. Enrichments in external arsenate and vanadate to phosphate-limited cultures act to suppress growth rates entirely, an effect not seen in phosphate replete conditions. Retardation of growth rates is attributed to mistaken uptake through ion promiscuity as evidenced by observations of significant intracellular accumulation of both arsenic and vanadium under phosphate limited conditions. We describe this novel co-limitation scenario as dependent antagonistic co-limitation (DAC), and suggest that this phenomenon of non-deliberate intracellular accumulation could be used as both a proxy of phosphate stress in the modern ocean and a possible marker of phosphate depletion limiting the duration of oceanic anoxic events.

Nitrogen, phosphorus and sulfur tri-doped carbon dots are specific and sensitive fluorescent probes for determination of chromium(VI) in water samples and in living cells.

A rapid, sensitive, and selective fluorometric assay is described for the determination of chromium(VI) in real waters and living cells. The method is making use of nitrogen, phosphorus, and sulfur tri-doped carbon dots (NPS-CDs) which have absorption/emission maxima at 360/505 nm/nm. Cr(VI) has an absorption maximum at 350 nm and causes an inner filter effect (IFE) on the blue fluorescence of the NPS-CDs. The NPS-CDs were hydrothermally synthesized using p-aminobenzenesulfonic acid and tetrakis(hydroxymethyl)phosphonium chloride as precursors. The NPS-CDs were characterized by transmission electron microscopy, X-ray diffraction, and several spectroscopic methods. They are biocompatible and negligibly cytotoxic when tested with HeLa cells and MCF-7 cells even after 48 h of incubation. The NPS-CDs were used as fluorescent probes for Cr(VI). The detection limit is 0.23 µM (three times standard deviation versus slope), and the linear response covers the 1 to 500 µM chromate concentration range. The NPS-CDs were applied to the determination of Cr(VI) in real waters and living cells (HeLa and MCF-7) and gave satisfying results. Graphical abstractSchematic representation of hydrothermal synthesis of nitrogen, phosphorus, and sulfur tri-doped carbon dots (NPS-CDs) for Cr(VI) detection via inner filter effect (IFE). NPS-CDs were applied to the determination of Cr(VI) in living cells (HeLa and MCF-7) with satisfying results.

Mechanistically derived Toxicant-mediated predator-prey model under Stoichiometric constraints.

Studies in ecological stoichiometry highlight that grazer dynamics are affected by insufficient food nutrient content (low phosphorus (P)/carbon (C) ratio) as well as excess food nutrient content (high P:C). Contaminant stressors affect all levels of the biological hierarchy, from cells to organs to organisms to populations to entire ecosystems. Eco-toxicological modeling under the framework of ecological stoichiometry predicts the risk of bio-accumulation of a toxicant under stoichiometric constraints. In this paper, we developed and analyzed a Lotka-Volterra type predator- prey model which explicitly tracks the environmental toxicant as well as the toxicant in the populations under stoichiometric constraints. Analytic, numerical, slow-fast steady state and bifurcation theory are employed to predict the risk of toxicant bio-accumulation under varying food conditions. In some cases, our model predicts different population dynamics, including wide amplitude limit cycles where producer densities exhibit very low values and may be in danger of stochastic extinction.

Bone marrow mesenchymal stem cell-derived exosomes alleviate high phosphorus-induced vascular smooth muscle cells calcification by modifying microRNA profiles.

Vascular calcification is a common complication in patients with chronic kidney disease (CKD). It is an important predictor of cardiovascular disease and all-cause mortality. Previous studies have confirmed that bone marrow mesenchymal stem cell (BMSC) therapy can reduce vascular calcification, but the specific mechanism is still controversial. In this study, we aimed to investigate the mechanisms of BMSC-derived exosomes (EXO) in improving vascular calcification. BMSCs were cultured and EXO were isolated using the Total Exosome Isolation Reagent. Human aortic vascular smooth muscle cells (HA-VSMCs) were cultured into three groups: control group, high phosphorus group, and high phosphorus plus EXO group. Then, indicators related to smooth muscle cell calcification and microRNA profiles were analyzed. BMSC-derived exosomes inhibited high phosphorus-induced calcification in HA-VSMCs. Besides, EXO treatment reduced calcium content and decreased the alkaline phosphatase (AKP) activity in high phosphorus co-incubated HA-VSMCs. MicroRNA (miRNA) and mRNA expression profiles analyses revealed that 63 miRNAs were significantly upregulated and 1424 genes were significantly downregulated in HA-VSMCs after EXO treatment. Functional miRNA-gene regulatory network revealed that mTOR, MAPK, and Wnt signaling pathway were involved in vascular calcification. BMSC-derived exosomes alleviated high phosphorus-induced calcification in HA-VSMC through modifying miRNA profiles.

Immediate and legacy effects of urban pollution on river ecosystem functioning: A mesocosm experiment.

Effluents from urban wastewater treatment plants (WWTP) consist of complex mixtures of substances that can affect processes in the receiving ecosystems. Some of these substances (toxic contaminants) stress biological activity at all concentrations, while others (e.g., nutrients) subsidize it at low concentrations and stress it above a threshold, causing subsidy-stress responses. Thus, the overall effects of WWTP effluents depend mostly on their composition and the dilution capacity of the receiving water bodies. We assessed the immediate and legacy effects of WWTP effluents in artificial streams, where we measured the uptake of soluble reactive phosphorus (SRP) by the biofilm, biomass accrual, benthic metabolism and organic matter decomposition (OMD). In a first phase (32 d), the channels were subjected to a gradient of effluent contribution, from pure stream water to pure effluent. WWTP effluent affected the ecosystem processes we measured, although we found no clear subsidy-stress patterns except for biofilm biomass accrual. Instead, most of the processes were subsidized, although they showed complex and process-specific patterns. Benthic metabolism and OMD were subsidized without saturation, as they peaked at medium and high levels of pollution, respectively, but they never fell below control levels. SRP uptake was the only process that decreased with increasing effluent concentration. In a second phase of the experiment (23 d), all channels were kept on pure stream water to analyse the legacy effects of the effluent. For most of the processes, there were clear legacy effects, which followed either subsidy, stress, or subsidy-stress patterns. SRP uptake capacity was stressed with increasing pollution legacy, whereas algal accrual and benthic metabolism continued being subsidized. Conversely, biofilm biomass accrual and OMD showed no legacy effects. Overall, the WWTP effluent caused complex and process-specific responses in our experiment, mainly driven by the mixed contribution of subsidizers and stressors. These results help improving our understanding of the effects of urban pollution on stream ecosystem functioning.