Characteristics of disinfection byproducts from dissolved organic matter during chlor(am)ination of source water in Tibetan Plateau, China.

The Tibetan Plateau, a typical high-altitude area, is less affected by human activities such as industrial development, and the external pollution to water sources is extremely low. Then it is also an important source of water samples for exploring the molecular characteristics of precursors in the dissolved organic matter (DOM) of disinfection byproducts (DBPs) in drinking water. Research data on DBPs in drinking water on the Tibet Plateau remains insufficient, leading to uncertainty about DBP contamination in the area. This study explores the formation potential of 35 typical DBPs, including 6 trihalomethanes (THMs), 9 haloacetic acids (HAAs), 2 halogenated ketones (HKs), 9 nitrosamines (NAs), and 9 aromatic DBPs, during chlorination and chloramination of typical source water samples in the Tibet Plateau of China. Moreover, in order to further investigate the characteristics of the generation of DBPs, the molecular composition of DOM in the collected water samples was characterized by Fourier transform ion cyclotron resonance mass spectrometry. The findings reveal that, for chlorination and chloramination, the average concentration of the five classes of DBPs was ranked as follows (chlorination, chloramination): HAAs (268.1 µg/L, 54.2 µg/L) > THMs (44.0 µg/L, 2.0 µg/L) > HKs (0.7 µg/L, 1.8 µg/L) > NAs (26.5 ng/L, 74.6 ng/L) > Aromatics (20.4 ng/L, 19.5 ng/L). The dominant compounds in THMs, HAAs, and NAs are trichloromethane, dichloroacetic acid, trichloroacetic acid, and nitrosopyrrolidine, respectively. This study highlights a significant positive correlation between DBP generation and UV254, SUV254, and the double bond equivalents of DOM in the source water. It systematically elucidates DOM molecular composition characteristics and DBP formation potential in high-altitude water sources, shedding light on key factors influencing DBP generation at the molecular level in high-altitude areas.

Chiral Nanoclusters as Alternative Therapeutic Strategies to Confront the Health Threat from Antibiotic-Resistant Pathogens.

Pseudomonas aeruginosa (P. aeruginosa), a drug-resistant Gram-negative pathogen, is listed among the "critical" group of pathogens by the World Health Organization urgently needing efficacious antibiotics in the clinics. Nanomaterials especially silver nanoparticles (AgNPs) due to the broad-spectrum antimicrobial activity are tested in antimicrobial therapeutic applications. Pathogens rapidly develop resistance to AgNPs; however, the health threat from antibiotic-resistant pathogens remains challenging. Here we present a strategy to prevent bacterial resistance to silver nanomaterials through imparting chirality to silver nanoclusters (AgNCs). Nonchiral AgNCs with high efficacy against P. aeruginosa causes heritable resistance, as indicated by a 5.4-fold increase in the minimum inhibitory concentration (MIC) after 9 repeated passages. Whole-genome sequencing identifies a Rhs mutation related to the wall of Gram-negative bacteria that possibly causes morphology changes in resistance compared to susceptible P. aeruginosa. Nevertheless, AgNCs with laevorotary chirality (l-AgNCs) induce negligible resistance even after 40 repeated passages and maintain a superior antibacterial efficiency at the MIC. l-AgNCs also show high cytocompatibility; negligible cytotoxicity to mammalian cells including JB6, H460, HEK293, and RAW264.7 is observed even at 30-fold MIC. l-AgNCs thus are examined as an alternative to levofloxacin in vivo, healing wound infections of P. aeruginosa efficaciously. This work provides a potential opportunity to confront the rising threat of antimicrobial resistance by developing chiral nanoclusters.

Facet-dependent transformation and toxicity of nanoscale zinc oxide in the synthetic saliva.

The nanoscale zinc oxide (n-ZnO) was used in food packages due to its superior antibacterial activity, resulting in potential intake of n-ZnO through the digestive system, wherein n-ZnO interacted with saliva. In recent, facet engineering, a technique for controlling the exposed facets, was applied to n-ZnO, whereas risk of n-ZnO with specific exposed facets in saliva was ignored. ZnO nanoflakes (ZnO-0001) and nanoneedles (ZnO-1010) with the primary exposed facets of {0001} and {1010} respectively were prepared in this study, investigating stability and toxicity of ZnO-0001 and ZnO-1010 in synthetic saliva. Both ZnO-0001 and ZnO-1010 partially transformed into amorphous Zn3(PO4)2 within 1 hr in the saliva even containing orgnaic components, forming a ZnO-Zn3(PO4)2 core-shell structure. Nevertheless, ZnO-1010 relative to ZnO-0001 would likely transform into Zn3(PO4)2, being attributed to superior dissolution of {1010} facet due to its lower vacancy formation energy (1.15 eV) than {0001} facet (3.90 eV). The toxicity of n-ZnO to Caco-2 cells was also dependent on the primary exposed facet; ZnO-0001 caused cell toxicity through oxidative stress, whereas ZnO-1010 resulted in lower cells viability than ZnO-0001 through oxidative stress and membrane damage. Density functional theory calculations illustrated that ·O2- was formed and released on {1010} facet, yet O22- instead of ·O2- was generated on {0001} facet, leading to low oxidative stress from ZnO-0001. All findings demonstrated that stability and toxicity of n-ZnO were dependent on the primary exposed facet, improving our understanding of health risk of nanomaterials.

Recent advances of semiconductor photocatalysis for water pollutant treatment: mechanisms, materials and applications.

Semiconductor photocatalysis has become an increasing area of interest for use in water treatment methods. This review systematically presents the recent developments of emerging semiconductor photocatalysis system and their application in the removal of water pollutants. A brief overview of the semiconductor photocatalysis mechanism involved with the generation of reactive oxygen species (ROS) is provided first. Then a detailed explanation of the development of TiO2-based, g-C3N4-based, and bismuth-based semiconductor materials and their applications in the degradation of water pollutants are highlighted with recent illustrative examples. Furthermore, the future prospects of semiconductor photocatalysis for water treatment are critically analyzed.

New insights into sulfur input induced methylmercury production and accumulation in paddy soil and rice.

Sulfur has a high affinity for mercury (Hg) and can serve as effective treating agent for Hg pollution. However, conflict effects between reducing Hg mobility and promoting Hg methylation by sulfur were found in recent studies, and there is a gap in understanding the potential mechanism of MeHg production under different sulfur-treated species and doses. Here, we investigated and compared the MeHg production in Hg-contaminated paddy soil and its accumulation in rice under elemental sulfur or sulfate treatment at a relatively low (500 mg·kg-1) or high (1000 mg·kg-1) level. The associated potential molecular mechanisms are also discussed with the help of density functional theory (DFT) calculation. Pot experiments demonstrate that both elemental sulfur and sulfate at high exposure levels increased MeHg production in soil (244.63-571.72 %) and its accumulation in raw rice (268.73-443.50 %). Coupling the reduction of sulfate or elemental sulfur and decrease of soil redox potential leads to the detachment of Hg-polysulfide complexes from the surface of HgS which can be explained by DFT calculations. Enhancement of free Hg and Fe release through reducing Fe(III) oxyhydroxides further promotes soil MeHg production. The results provide clues for understanding the mechanism by which exogenous sulfur promotes MeHg production in paddies and paddy-like environments and give new insights for decreasing Hg mobility by regulating soil conditions.

Magnetic nanoparticle-assisted colonization of synthetic bacteria on plant roots for improved phytoremediation of heavy metals.

Phytoremediation is a facile strategy to remove environmental heavy metals by using metal-accumulating plants from the rhizosphere environment. However, its efficiency is frequently compromised by the weak activity of rhizosphere microbiomes. This study developed a magnetic nanoparticle-assisted root colonization technique of synthetic functional bacteria to regulate rhizosphere microbiome composition for enhanced phytoremediation of heavy metals. The iron oxide magnetic nanoparticles with the size of 15-20 nm were synthesized and grafted by chitosan, a natural bacterium-binding polymer. The synthetic Escherichia coli SynEc2, which highly exposed an artificial heavy metal-capturing protein, was then introduced with the magnetic nanoparticles to bind the Eichhornia crassipes plants. Confocal microscopy, scanning electron microscopy, and microbiome analysis revealed that the grafted magnetic nanoparticles strongly promoted colonization of the synthetic bacteria on the plant roots, leading to remarkable change of rhizosphere microbiome composition, with the increase in the abundance of Enterobacteriaceae, Moraxellaceae, and Sphingomonadaceae. Histological staining and biochemical analysis further showed that the combination of SynEc2 and the magnetic nanoparticles protected the plants from heavy metal-induced tissue damage, and increased plant weights from 29 g to 40 g. Consequently, the plants with the assistance of synthetic bacteria and the magnetic nanoparticles in combination exhibited much higher heavy metal-removing capacity than the plants treated by the synthetic bacteria or the magnetic nanoparticles alone, leading to the decrease in the heavy metal levels from 3 mg/L to 0.128 mg/L for cadmium, and to 0.032 mg/L for lead. This study provided a novel strategy to remodel rhizosphere microbiome of metal-accumulating plants by integrating synthetic microbes and nanomaterials for improving the efficiency of phytoremediation.

Generation Mechanism of Perfluorohexanesulfonic Acid from Polyfluoroalkyl Sulfonamide Derivatives During Chloramination in Drinking Water.

Per- and polyfluoroalkyl substances (PFASs), including perfluorohexanesulfonic acid (PFHxS), as emerging persistent organic pollutants widely detected in drinking water, have drawn increasing concern. The PFHxS contamination of drinking water always results from direct and indirect sources, especially the secondary generations through environmental transformations of precursors. However, the mechanism of the transformation of precursors to PFHXS during the drinking water treatment processes remains unclear. Herein, the potential precursors and formation mechanisms of PFHxS were explored during drinking water disinfection. Simultaneously, the factors affecting PFHxS generation were also examined. This study found PFHxS could be generated from polyfluoroalkyl sulfonamide derivatives during chlorination and chloramination. The fate and yield of PFHxS varied from different precursors and disinfection processes. In particular, monochloramine more favorably formed PFHxS. Several perfluoroalkyl oxidation products and decarboxylation intermediates were detected and identified in the chloraminated samples using Fourier-transform ion cyclotron resonance mass spectrometry. Combined with density functional theory calculations, the results indicated that the indirect oxidation via the attack of the nitrogen atom in sulfonamide groups might be the dominant pathway for generating PFHxS during chloramination, and the process could be highly affected by the monochloramine dose, pH, and temperature. This study provides important evidence of the secondary formation of PFHxS during drinking water disinfection and scientific support for chemical management of PFHxS and PFHxS-related compounds.

Vital Environmental Sources for Multitudinous Fluorinated Chemicals: New Evidence from Industrial Byproducts in Multienvironmental Matrices in a Fluorochemical Manufactory.

Direct emissions from fluorochemical manufactory are an important source of per- and polyfluoroalkyl substances (PFASs) to the environment. In this study, a wide range of PFASs, including 8 legacy PFASs, 8 long-chain perfluoroalkyl carboxylic acids (PFCAs), and 40 emerging PFASs, were investigated through a target screening in multienvironmental matrices from a fluorochemical manufactory in China. Indoor dust was the most polluted matrix, wherein 52 PFASs were detected, and the median concentration of long-chain PFCA was 276 ng/g. A high level of short-chain PFAS in total suspended particles (median concentration = 416 ng/m3) and the effluent in the manufactory (Σ48PFAS = 212 µg/L) will undoubtedly increase the burden on the surrounding environment. Twenty-four industrial byproducts were ascertained to be generated during the electrochemical fluorination (ECF) process, and eight fluorinated alternatives were considered to be produced during product development. Twelve PFASs were quantified for the first time in the working environments. Perfluoropropane sulfonic acid, perfluoro (2-ethoxyethane) sulfonic acid (PFEESA), and 2-perfluorohexyl ethanoic acid are abundant fluorinated alternatives, with median levels of 1187-17204 ng/g in the dust. Significant positive correlations between ECF-related PFAS products and byproducts indicate that the detected values are strongly connected with the industrial source. Hierarchical cluster analysis further manifests their affiliation. Our findings raise the need for further investigations of emerging PFAS (including the first report of PFAS, such as PFEESA, in the environment) which may be released during the production process in the fluorochemical manufactories.

Effect of polar/non-polar facets on the transformation of nanoscale ZnO in simulated sweat and potential impacts on the antibacterial activity.

The use of nanoscale zinc oxide (n-ZnO) in the personal care products would cause interactions between n-ZnO and human sweat. Facet engineering has been applied to n-ZnO to improve its activity. Nevertheless, it is not clear whether the exposed facet would affect transformation of n-ZnO in sweat. Herein, we prepared ZnO nanoneedles with the dominant (1010) non-polar facet (i.e., ZnO-1010) and ZnO nanoflakes with the dominant (0001) polar facet (i.e., ZnO-0001), respectively. We found that n-ZnO can undergo chemical transformation in the simulated sweat within 168 h or 24 h, transforming into amorphous materials and Zn3(PO4)20.4 H2O and/or Na(ZnPO4)·H2O. Given the rate constant (e.g., 0.093 h-1 for ZnO-0001 vs. 0.033 h-1 for ZnO-1010) of ZnO depletion and components of the precipitate from the simulated sweat, nevertheless, the transformation is highly dependent on the dominant exposed facet of n-ZnO. The ZnO-0001 relative to ZnO-1010 would likely undergo chemical transformation, demonstrating that the (0001) polar facet compared to (1010) non-polar facet had a superior activity to the dihydrogen phosphate anions in the simulated sweat, which is supported by density functional theory calculations. The chemical transformation can affect the antibacterial activity of n-ZnO to E. coli, moderating the toxicity due to a great decrease in the concentration of the dissolved zinc. In total, our findings provided insights into the facet-dependent transformation for n-ZnO in the simulated sweat, improving our understanding of potential risk of n-ZnO.

Roles of plant-associated microorganisms in regulating the fate of Hg in croplands: A perspective on potential pathways in maintaining sustainable agriculture.

In heavy metal-contaminated croplands, plant-associated microorganisms play important roles in the adaptation of crops to heavy metals. Plant-associated microbes can interact with Hg and stimulate plant resistance to Hg toxicity, which is crucial for impeding Hg accumulation along the food chain. The roles of rhizosphere microorganisms for the improvement of plant growth and Hg resistance have drawn great research attention. However, the interactions among plant-endophyte-Hg have been neglected although they might be important for in vivo Hg detoxification. In this study, we systematically summarized 1) the roles of plant-associated microorganisms in Hg detoxification and plant growth, 2) Hg methylation and demethylation driven by plant-associated microbes, 3) the relationships between plant-associated microbes and Hg biogeochemical cycling. The possible mechanisms underlying crop-endophyte-Hg interactions were discussed, although limited studies on this aspect are available to date. The challenges and perspectives of plant-endophytes in dampening Hg phytotoxicity and controlling Hg accumulation in croplands were proposed on the basis of the present knowledge. Taken together, this work provides evidence for further understanding the interactions between soil-plant-endophyte-Hg systems and as well as new interpretations and perspectives into regulating the fate of Hg in croplands.

Mercury Reduction, Uptake, and Species Transformation by Freshwater Alga Chlorella vulgaris under Sunlit and Dark Conditions.

As a major entry point of mercury (Hg) to aquatic food webs, algae play an important role in taking up and transforming Hg species in aquatic ecosystems. However, little is known how and to what extent Hg reduction, uptake, and species transformations are mediated by algal cells and their exudates, algal organic matter (AOM), under either sunlit or dark conditions. Here, using Chlorella vulgaris (CV) as one of the most prevalent freshwater model algal species, we show that solar irradiation could enhance the reduction of mercuric Hg(II) to elemental Hg(0) by both CV cells and AOM. AOM reduced more Hg(II) than algal cells themselves due to cell surface adsorption and uptake of Hg(II) inside the cells under solar irradiation. Synchrotron radiation X-ray absorption near-edge spectroscopy (SR-XANES) analyses indicate that sunlight facilitated the transformation of Hg to less bioavailable species, such as ß-HgS and Hg-phytochelatins, compared to Hg(Cysteine)2-like species formed in algal cells in the dark. These findings highlight important functional roles and potential mechanisms of algae in Hg reduction and immobilization under varying lighting conditions and how these processes may modulate Hg cycling and bioavailability in the aquatic environment.

Mobilization and methylation of mercury with sulfur addition in paddy soil: Implications for integrated water-sulfur management in controlling Hg accumulation in rice.

Sulfur-fertilizer is commonly applied in croplands and in immobilizing Hg in contaminated soil. However, there is still great uncertainty and controversy concerning Hg transportability and transformation when supplying sulfur in paddies with complex conditions. Herein, we explored the effect of adding sulfate in paddy soil at different rice growth stages on soil Hg release and MeHg accumulation in rice and uncovered the correlation between sulfur induced MeHg production and the dynamically changed soil Eh, dissolved Fe, and dissolved organic carbon (DOC). In specific, sulfate addition at early stages (flooding period) triggered the decrease of Eh and increase of DOC and dissolved Fe, which in turn promoted Hg release and favored MeHg generation (increased by 235.19-555.07% vs control). Interestingly, adding sulfate at late stages (drainage condition), as compared with that at early stages, alleviated Hg release and MeHg production accompanied by the increase of Eh and decrease of dissolved Fe and DOC. The microcosmic experiment further confirmed the reduction of sulfate to sulfide promoted the change of Eh, thereby stimulating HgS dissolution in soil extract. The results give clues on the rational application of sulfur-fertilizer and through the water-sulfur fertilizer management considering the correspondingly changed soil conditions to diminish Hg bioavailability and MeHg production in paddies and paddy-like environments.

Detection and remediation of mercury contaminated environment by nanotechnology: Progress and challenges.

Hg pollution is a global concern due to its high ecotoxicity and health risk to human beings. A comprehensive understanding of the fast-developed technology applied in determining and controlling Hg pollution is beneficial for risk assessment and field remediation. Herein, we mainly assembled the recent progress on Hg treatment in the environment by nanotechnology. The advantages and disadvantages of the conventional and nanotechnology-based methods commonly used in water-/soil-Hg remediation were compared and summarized. Specifically, green nanomaterials derived from plant tissues (e.g., nanocellulose) have prominent merits in remediation of Hg contaminated environments, including high efficiency in Hg removal, low cost, environment-friendly, and easily degradable. Based on the theories of Hg biogeochemistry and existed researches, four promising pathways are proposed, 1) developing surface-modified green nanocellulose with high selectivity and affinity towards Hg; 2) designing effective dispersants in preventing nanocellulose from agglomeration in soil; 3) mediating soil properties by adding green nanomaterials-based fertilizers; 4) improving plant-Hg-extract capacity with green nanomaterials addition. Briefly, more efficient and available approaches are still expected to be developed and implemented in the natural environment for Hg remediation.

The Transient Receptor Potential Channel Yvc1 Deletion Recovers the Growth Defect of Calcineurin Mutant Under Endoplasmic Reticulum Stress in Candida albicans.

Transient receptor potential (TRP) channel Yvc1 was related with hyphal growth, oxidative stress response, and pathogenicity. Calcineurin subunit Cnb1 was activated immediately in yeasts when exposed to severe stimulation. However, the relationship between Yvc1 and Cnb1-governed calcium ions and endoplasmic reticulum (ER) stress response remains unrevealed. In this study, we found that the mutant cnb1Δ/Δ was sensitive to TN, which was related with the overexpression of membrane calcium ion channels that could increase the cytosol calcium concentration. However, the growth of the cnb1Δ/Δyvc1Δ/Δ mutant was recovered and its cell vitality was better than the cnb1Δ/Δ strain. Meanwhile, the cellular calcium concentration was decreased and its fluctuation was weakened under ER stress in the cnb1Δ/Δyvc1Δ/Δ strain. To verify the regulation role of Yvc1 in the calcium concentration, we found that the addition of CaCl2 led to the worse viability, while the growth state was relieved under the treatment of EGTA in the cnb1Δ/Δ strain. In conclusion, the deletion of YVC1 could reduce the cellular calcium and relieve the ER stress sensitivity of the cnb1Δ/Δ strain. Thereby, our findings shed a novel light on the relationship between the Yvc1-governed cellular calcium concentration and ER stress response in C. albicans.

Oleic Acid and Eicosapentaenoic Acid Reverse Palmitic Acid-induced Insulin Resistance in Human HepG2 Cells via the Reactive Oxygen Species/JUN Pathway.

Oleic acid (OA), a monounsaturated fatty acid (MUFA), has previously been shown to reverse saturated fatty acid palmitic acid (PA)-induced hepatic insulin resistance (IR). However, its underlying molecular mechanism is unclear. In addition, previous studies have shown that eicosapentaenoic acid (EPA), a ω-3 polyunsaturated fatty acid (PUFA), reverses PA-induced muscle IR, but whether EPA plays the same role in hepatic IR and its possible mechanism involved need to be further clarified. Here, we confirmed that EPA reversed PA-induced IR in HepG2 cells and compared the proteomic changes in HepG2 cells after treatment with different free fatty acids (FFAs). A total of 234 proteins were determined to be differentially expressed after PA+OA treatment. Their functions were mainly related to responses to stress and endogenous stimuli, lipid metabolic process, and protein binding. For PA+EPA treatment, the PA-induced expression changes of 1326 proteins could be reversed by EPA, 415 of which were mitochondrial proteins, with most of the functional proteins involved in oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle. Mechanistic studies revealed that the protein encoded by JUN and reactive oxygen species (ROS) play a role in OA- and EPA-reversed PA-induced IR, respectively. EPA and OA alleviated PA-induced abnormal adenosine triphosphate (ATP) production, ROS generation, and calcium (Ca2+) content. Importantly, H2O2-activated production of ROS increased the protein expression of JUN, further resulting in IR in HepG2 cells. Taken together, we demonstrate that ROS/JUN is a common response pathway employed by HepG2 cells toward FFA-regulated IR.

Transcription profiling-guided remodeling of sulfur metabolism in synthetic bacteria for efficiently capturing heavy metals.

Heavy metal contamination is becoming a global problem threatening human health. Heavy metal removal by engineered microbes by cellular adsorption and uptake is a promising strategy for treatment of heavy metal contamination. However, this strategy is confronted with limited heavy metal-capturing elements. In this study, we performed a transcription profiling-guided strategy for construction of heavy metal-capturing synthetic bacteria. Transcription profiling of a heavy metal-tolerating Cupriavidus taiwanensis strain revealed up-regulation of sulfur metabolism-related operons (e.g., iscSAU and moaEDAB) by Pb2+ and Cd2+. A synthetic Escherichia coli strain, EcSSMO, was constructed by design of a synthetic sulfur metabolism operon (SSMO) based on iscSAU/moaEDAB. Biochemical analysis and X-ray photoelectron spectroscopy (XPS) revealed that the synthetic bacteria had remodeled sulfur metabolism and enhanced heavy metal-tolerating capacity, with higher surviving EcSSMO cells than the surviving control cells Ec0 (not containing SSMO) at 50 mg/L of Pb2+ and Cd2+ (>92 % versus <10 %). Moreover, EcSSMO exhibited much higher heavy metal-capturing capacity than Ec0, removing>90 % of Pb2+ and Cd2+ at 5 mg/L of Pb2+ and Cd2+, and >40 % of both heavy metals even at 50 mg/L of Pb2+ and Cd2+. This study reveals emphasizes feasibility of transcription profiling-guided construction of synthetic organisms by large-scale remodeling metabolic network.

Long-range atmospheric transport and alpine condensation of short-chain chlorinated paraffins on the southeastern Tibetan Plateau.

Pristine alpine regions are ideal regions for investigating the long-range atmospheric transport and cold trapping effects of short chain chlorinated paraffins (SCCPs). The concentrations and alpine condensation of SCCPs were investigated in lichen samples collected from the southeastern Tibetan Plateau. The concentrations of SCCPs ranged from 3098 to 6999 ng/g lipid weight (lw) and appeared to have an increasing trend with altitude. For congeners, C10 dominated among all the congener groups. The different environmental behavior for different congener groups was closely related to their octanol-air partition coefficient (Koa). C10 congeners showed an increasing trend with altitude, whereas C13 congeners were negatively correlated with altitude. Volumetric bioconcentration factors (BCF) of SCCPs reached 8.71 in lichens, which were higher than other semivolatile organic compounds (SVOCs) such as organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), and hexabromocyclododecane (HBCD). These results suggested that SCCPs were prone to accumulate in the lichen from the air and provided evidence for the role of lichens as a suitable atmospheric indicator in the Tibetan Plateau.

The V-ATPase regulates localization of the TRP Ca2+ channel Yvc1 in response to oxidative stress in Candida albicans.

The vacuolar-type H+-ATPase (V-ATPase) is a highly conserved protein complex among the eukaryotic cells. We previously revealed that both the V-ATPase and the transient receptor potential (TRP) channel Yvc1 are involved in oxidative stress response (OSR). However, the relationship between V-ATPase and Yvc1 during OSR remains unknown. In this study, disruption of the V-ATPase-encoding genes VPH2 and TFP1, similar with disruption of YVC1, caused H2O2 hypersensitivity and enhancement of vacuolar membrane permeability (VMP) under oxidative stress. Further investigations showed that unlike the wild type strain with vacuole membrane-localized Yvc1, both vph2Δ/Δ and tfp1Δ/Δ had Yvc1 localization in the vacuole cavity, indicating that disruption of VPH2 or TFP1 impaired normal vacuolar membrane-localization of Yvc1. Interestingly, addition of CaCl2 alleviated the growth defect of vph2Δ/Δ and tfp1Δ/Δ under oxidative stress, leading to prevention of VMP, decrease in ROS levels and activation of OSR. In contrast, addition of the Ca2+ chelating agent glycol-bis-(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA) aggravated H2O2 hypersensitivity of the mutants. These results showed that the V-ATPase plays an important role in maintenance of normal Yvc1 localization, which contributes to Ca2+ transport from the vacuoles to the cytosol for activation of OSR. This work sheds a novel light on the interaction between V-ATPase and Ca2+ transport for regulation of OSR in C. albicans.

The inositol polyphosphate kinase Ipk1 transcriptionally regulates mitochondrial functions in Candida albicans.

Inositol polyphosphates (IPs) is an important family of signaling molecules that regulate multiple cellular processes, such as chromatin remodeling, transcription and mRNA export. Inositol polyphosphate kinases, as the critical enzymes for production and transformation of IPs, directly determine the intracellular levels of IPs and therefore are involved in many cellular processes. However, its roles in Candida albicans, the leading fungal pathogen in human beings, remain to be investigated. In this study, we identified the inositol polyphosphate kinase Ipk1 in C. albicans and found that it localizes in the nucleus. Moreover, in the ipk1Δ/Δ mutant, the activity of mitochondrial respiratory chain complexes and the mitochondrial function was severely impaired, which were associated with down-regulation of mitochondrial function-related genes revealed by transcription profiling analysis. The ipk1Δ/Δ mutant also displayed hypersensitivity to a series of environmental stresses, such as antifungal drugs, oxidants, cell wall perturbing agents and macrophage attacks, followed by attenuation of virulence in a mouse systematic infection model. These findings firstly reported the importance of inositol polyphosphate kinase Ipk1 in C. albicans, especially its role in mitochondrial function maintenance and pathogenicity.

Vacancy-induced toxicity of CoSe2 nanomaterials in rat lung macrophages.

Rich vacancies of semiconductor nanomaterials (NMs) give rise to great enhancement of their physical and chemical properties such as magnetic, catalytic, optical, etc. These NMs possessing extensive applications could inevitably enter into the environment and increase the toxic effects on organisms, so it is imperative to investigate the cytotoxicity of NMs with different types of vacancies. Here, one-dimensional cobalt selenide (CoSe2) NMs with different vacancies were synthesized through the same precursor while calcined at different temperatures (P-CoSe2 which calcined at 200 °C and N-CoSe2 which calcined at 230 °C). According to the positron annihilation spectrum, the VSeSe vacancy associate in P-CoSe2 was endowed with two positive charges, while the VCoCoCoSeSe vacancy associate in N-CoSe2 possessed four negative charges. Cell viability assays revealed that N-CoSe2 had higher toxicity to macrophages than P-CoSe2, which was attributed to higher levels of intracellular reactive oxygen species induced by N-CoSe2. Further investigation showed that N-CoSe2 had higher affinity to the mitochondrion-targeting peptide, leading to its preferential distribution in the mitochondria and consequent induction of mitochondrial superoxide production. In contrast, P-CoSe2 exhibited higher affinity to the endoplasmic reticulum (ER)-targeting peptide, facilitating its preferential distribution in the ER and the nuclei and causing higher damage to both organelles as compared to N-CoSe2. These results demonstrated that type of surface vacancies significantly affected biodistribution of NMs in subcellular organelles, which contributed to differential biological behaviors of the NMs.