Inorganic ions activate lineage-specific gene regulatory networks.

Inorganic biomaterials have been shown to direct cellular responses, including cell-cell and cell-matrix interactions. Notably, ions released from these inorganic biomaterials play a vital role in defining cell identity, and promoting tissue-specific functions. However, the effect of inorganic ions on cellular functions have yet to be investigated at the transcriptomic level, representing a critical knowledge gap in the development of next-generation bioactive materials. To address this gap, we investigated the impact of various inorganic ions including silver, copper, titanium, and platinum on human mesenchymal stem cells (hMSCs). Our finding showed that silver and copper induce osteogenic and chondrogenic differentiation respectively, through enrichment of lineage-specific gene expression program. In particular, silver effectively induced Wingless/Integrated (Wnt) and mitogen-activated protein kinase (MAPK) signaling, which are vital for osteogenesis. On the other hand, copper specifically stimulated Transforming growth factor beta (TGFß) signaling, while suppressing Janus kinase/signal transducers and activators of transcription (JAK-STAT) signaling, thereby promoting chondrogenesis. In contrast, platinum, and tantalum, ions didn't stimulate regenerative responses. Together, our findings highlight the potential of inorganic biomaterials in tissue regeneration strategies, which currently rely largely on growth factors and small molecule therapeutics. STATEMENT OF SIGNIFICANCE: This research emphasizes the critical role of bioactive inorganic ions in controlling lineage-specific gene expression patterns in mesenchymal stem cells, effectively modulating the transcriptome landscape and directing cell fate. The study lays the foundation for a systematic database of biomaterial candidates and their effects on cellular functions, which will ultimately streamline the translation of new biomaterials into clinical applications.

A multi-crosslinking strategy of organic and inorganic compound bio-adhesive polysaccharide-based hydrogel for wound hemostasis.

Polysaccharides are naturally occurring polymers with exceptional biodegradable and biocompatible qualities that are used as hemostatic agents. In this study, photoinduced CC bond network and dynamic bond network binding was used to give polysaccharide-based hydrogels the requisite mechanical strength and tissue adhesion. The designed hydrogel was composed of modified carboxymethyl chitosan (CMCS-MA) and oxidized dextran (OD), and introduced hydrogen bond network through tannic acid (TA) doping. Halloysite nanotubes (HNTs) were also added, and the effects of various doping amount on the performance of the hydrogel were examined, in order to enhance the hemostatic property of hydrogel. Experiments on vitro degradation and swelling demonstrated the strong structural stability of hydrogels. The hydrogel has improved tissue adhesion strength, with a maximum adhesion strength of 157.9 kPa, and demonstrated improved compressive strength, with a maximum compressive strength of 80.9 kPa. Meanwhile, the hydrogel had a low hemolysis rate and had no inhibition on cell proliferation. The created hydrogel exhibited a significant aggregation effect on platelets and a reduced blood clotting index (BCI). Importantly, the hydrogel can quickly adhere to seal the wound and has good hemostatic effect in vivo. Our work successfully prepared a polysaccharide-based bio-adhesive hydrogel dressing with stable structure, appropriate mechanical strength, and good hemostatic properties.

Proteomic, Biochemical, and Morphological Analyses of the Effect of Silver Nanoparticles Mixed with Organic and Inorganic Chemicals on Wheat Growth.

Wheat is vulnerable to numerous diseases; on the other hand, silver nanoparticles (AgNPs) exhibit a sterilizing action. To understand the combined effects of AgNPs with nicotinate and potassium nitrate (KNO3) for plant growth and sterilization, a gel- and label-free proteomics was performed. Root weight was promoted by the treatment of AgNPs mixed with nicotinate and KNO3. From a total of 5557 detected proteins, 90 proteins were changed by the mixture of AgNPs, nicotinate, and KNO3; among them, 25 and 65 proteins increased and decreased, respectively. The changed proteins were mainly associated with redox and biotic stress in the functional categorization. By immunoblot analysis, the abundance of glutathione reductase/peroxiredoxin and pathogen-related protein three significantly decreased with the mixture. Furthermore, from the changed proteins, the abundance of starch synthase and lipoxygenase significantly increased and decreased, respectively. Through biochemical analysis, the starch contents increased with the mixture. The application of esculetin, which is a lipoxygenase inhibitor, increased the weight and length of the root. These results suggest that the AgNPs mixed with nicotinate and KNO3 cause positive effects on wheat seedlings by regulating pathogen-related protein and reactive-oxygen species scavenging. Furthermore, increasing starch and decreasing lipoxygenase might improve wheat growth.

Mechanisms of immune response to inorganic nanoparticles and their degradation products.

Careful assessment of the biological fate and immune response of inorganic nanoparticles is crucial for use of such carriers in drug delivery and other biomedical applications. Many studies have elucidated the cellular and molecular mechanisms of the interaction of inorganic nanoparticles with the components of the immune system. The biodegradation and dissolution of inorganic nanoparticles can influence their ensuing immune response. While the immunological properties of inorganic nanoparticles as a function of their physicochemical properties have been investigated in detail, little attention has been paid to the immune adverse effects towards the degradation products of these nanoparticles. To fill this gap, we herein summarize the cellular mechanisms of immune response to inorganic nanoparticles and their degradation products with specific focus on immune cells. We also accentuate the importance of designing new methods and instruments for the in situ characterization of inorganic nanoparticles in order to assess their safety as a result of degradation. This review further sheds light on factors that need to be considered in the design of safe and effective inorganic nanoparticles for use in delivery of bioactive and imaging agents.

Using semantics to scale up evidence-based chemical risk-assessments.

BACKGROUND: The manual processes used for risk assessments are not scaling to the amount of data available. Although automated approaches appear promising, they must be transparent in a public policy setting. OBJECTIVE: Our goal is to create an automated approach that moves beyond retrieval to the extraction step of the information synthesis process, where evidence is characterized as supporting, refuting, or neutral with respect to a given outcome. METHODS: We combine knowledge resources and natural language processing to resolve coordinated ellipses and thus avoid surface level differences between concepts in an ontology and outcomes in an abstract. As with a systematic review, the search criterion, and inclusion and exclusion criterion are explicit. RESULTS: The system scales to 482K abstracts on 27 chemicals. Results for three endpoints that are critical for cancer risk assessments show that refuting evidence (where the outcome decreased) was higher for cell proliferation (45.9%), and general cell changes (37.7%) than for cell death (25.0%). Moreover, cell death was the only end point where supporting claims were the majority (61.3%). If the number of abstracts that measure an outcome was used as a proxy for association there would be a stronger association with cell proliferation than cell death (20/27 chemicals). However, if the amount of supporting evidence was used (where the outcome increased) the conclusion would change for 21/27 chemicals (20 from proliferation to death and 1 from death to proliferation). CONCLUSIONS: We provide decision makers with a visual representation of supporting, neutral, and refuting evidence whilst maintaining the reproducibility and transparency needed for public policy. Our findings show that results from the retrieval step where the number of abstracts that measure an outcome are reported can be misleading if not accompanied with results from the extraction step where the directionality of the outcome is established.

Prediction of permeability across intestinal cell monolayers for 219 disparate chemicals using in vitro experimental coefficients in a pH gradient system and in silico analyses by trivariate linear regressions and machine learning.

For medicines, the apparent membrane permeability coefficients (Papp) across human colorectal carcinoma cell line (Caco-2) monolayers under a pH gradient generally correlate with the fraction absorbed after oral intake. Furthermore, the in vitro Papp values of 29 industrial chemicals were found to have an inverse association with their reported no-observed effect levels for hepatotoxicity in rats. In the current study, we expanded our influx permeability predictions for the 90 previously investigated chemicals to both influx and efflux permeability predictions for 207 diverse primary compounds, along with those for 23 secondary compounds. Trivariate linear regression analysis found that the observed influx and efflux logPapp values determined by in vitro experiments significantly correlated with molecular weights and the octanol-water distribution coefficients at apical and basal pH levels (pH 6.0 and 7.4, respectively) (apical to basal, r = 0.76, n = 198; and basal to apical, r = 0.77, n = 202); the distribution coefficients were estimated in silico. Further, prediction accuracy was enhanced by applying a light gradient boosting machine learning system (LightGBM) to estimate influx and efflux logPapp values that incorporated 17 and 19 in silico chemical descriptors (r = 0.83-0.84, p < 0.001). The determination in vitro and/or prediction in silico of permeability coefficients across intestinal cell monolayers of a diverse range of industrial chemicals/food components/medicines could contribute to the safety evaluations of oral intakes of general chemicals in humans. Such new alternative methods could also reduce the need for animal testing during toxicity assessment.

Inhibition of the newly discovered ß­carbonic anhydrase from the protozoan pathogen Trichomonas vaginalis with inorganic anions and small molecules.

The protozoan pathogen Trichomonas vaginalis encodes two carbonic anhydrases (CAs, EC 4.2.1.1) belonging to the ß-class. One of these enzymes, T. vaginalis carbonic anhydrase 1 (TvaCA1), was recently cloned and characterized by our group, and its X-ray crystal structure reported. No inhibitors of this enzyme were reported up until now. Here we investigated the inhibition of TvaCA1 with inorganic anions and small molecules and observed that thiocyanate, cyanide, selenite, selenocyanate and divanadate are sub-millimolar inhibitors, whereas sulfamide, sulfate, phenylboronic acid and phenylarsonic acid are micromolar inhibitors. Finding effective TvaCA1 inhibitors may be useful for developing new antiprotozoan drugs.

A multi-parametric screening platform for photosynthetic trait characterization of microalgae and cyanobacteria under inorganic carbon limitation.

Microalgae and cyanobacteria are considered as important model organisms to investigate the biology of photosynthesis; moreover, they are valuable sources of biomolecules for several biotechnological applications. Understanding the species-specific traits of photosynthetic electron transport is extremely important, because it contributes to the regulation of ATP/NADPH ratio, which has direct/indirect links to carbon fixation and other metabolic pathways and thus overall growth and biomass production. In the present work, a cuvette-based setup is developed, in which a combination of measurements of dissolved oxygen, pH, chlorophyll fluorescence and NADPH kinetics can be performed without disturbing the physiological status of the sample. The suitability of the system is demonstrated using a model cyanobacterium Synechocystis sp. PCC6803, as well as biofuel-candidate microalgae species, such as Chlorella sorokiniana, Dunaliella salina and Nannochloropsis limnetica undergoing inorganic carbon (Ci) limitation. Inorganic carbon limitation, induced by photosynthetic Ci uptake under continuous illumination, caused a decrease in the effective quantum yield of PSII (Y(II)) and loss of oxygen-evolving capacity in all species investigated here; these effects were largely recovered by the addition of NaHCO3. Detailed analysis of the dark-light and light-dark transitions of NADPH production/uptake and changes in chlorophyll fluorescence kinetics revealed species- and condition-specific responses. These responses indicate that the impact of decreased Calvin-Benson cycle activity on photosynthetic electron transport pathways involving several sections of the electron transport chain (such as electron transfer via the QA-QB-plastoquinone pool, the redox state of the plastoquinone pool) can be analyzed with high sensitivity in a comparative manner. Therefore, the integrated system presented here can be applied for screening for specific traits in several significant species at different stages of inorganic carbon limitation, a condition that strongly impacts primary productivity.

Autophagy Modulated by Inorganic Nanomaterials.

With the rapid development of nanotechnology, inorganic nanomaterials (NMs) have been widely applied in modern society. As human exposure to inorganic NMs is inevitable, comprehensive assessment of the safety of inorganic NMs is required. It is well known that autophagy plays dual roles in cell survival and cell death. Moreover, inorganic NMs have been proven to induce autophagy perturbation in cells. Therefore, an in-depth understanding of inorganic NMs-modulated autophagy is required for the safety assessment of inorganic NMs. This review presents an overview of a set of inorganic NMs, consisting of iron oxide NMs, silver NMs, gold NMs, carbon-based NMs, silica NMs, quantum dots, rare earth oxide NMs, zinc oxide NMs, alumina NMs, and titanium dioxide NMs, as well as how each modulates autophagy. This review emphasizes the potential mechanisms underlying NMs-induced autophagy perturbation, as well as the role of autophagy perturbation in cell fate determination. Furthermore, we also briefly review the potential roles of inorganic NMs-modulated autophagy in diagnosis and treatment of disease.

Biomimetic organic-inorganic hybrid hydrogel electrospinning periosteum for accelerating bone regeneration.

Periosteum as an important component in the construct of bone is mainly responsible for providing nourishment and regulating osteogenic differentiation. When bone defect happens, the functionality of periosteum will also be influenced, furthermore, it will finally hamper the process of bone regeneration. However, fabrication of an artificial periosteum with the capabilities in accelerating angiogenesis and osteogenesis in the defect area is still a challenge for researchers. In this study, we fabricated an organic-inorganic hybrid biomimetic periosteum by electrospinning, which can induce mineralization in situ and control the ions release for long-term in local area. Further, this system exhibited potential capabilities in promoting in vitro, which means the potentiality in accelerating bone regeneration in vivo. Calcium phosphate nanoparticles (CaPs) were fabricated by emulsion method, then CaPs were further incorporated with gelatin-methacryloyl (GelMA) by electrospinning fibers to construct the hybrid hydrogel fibers. The fibers exhibited satisfactory morphology and mechanical properties, additionally, controlled ions release could be observed for over 10 days. Further, significant mineralization was proved on the surface of hybrid fibers after 7 days and 14 days' co-incubation with simulated body fluid (SBF). Then, favorable biocompatibility of the hybrid fibers was approved by co-cultured with MC3T3-E1 cells. Finally, the hybrid fibers exhibited potential capabilities in promoting angiogenesis and osteogenesis by co-culture with HUVECs and MC3T3-E1 cells. This biomimetic organic-inorganic hybrid hydrogel electrospinning periosteum provided a promising strategy to develop periosteum biomaterials with angiogenesis and osteogenesis capabilities.

Natural Inorganic Ingredients in Wound Healing.

BACKGROUND: One of the major clinical challenges is to achieve a rapid and efficient treatment of complex chronic wounds. Nowadays, most wound dressings currently available are unable to find a solution to the challenges of resistance to bacterial infection, protein adsorption and increased levels of exudates. Natural inorganic ingredients (clay minerals, metal cations, zeolites, etc.) could be the key to solve the problem satisfactorily. Some of these materials have shown biocompatibility and ability to enhance cell adhesion, proliferation and cellular differentiation and uptake. Besides, some natural inorganic ingredients effectively retain drugs, allowing the design of drug delivery matrices. OBJECTIVE: Possibilities of natural inorganic ingredients in wound healing treatments have been reviewed, the following sections have been included: 1. Introduction 2. Functions of Inorganic Ingredients in wound healing 2.1. Antimicrobial effects 2.2. Hemostatic effects 3. Clay minerals for wound healing 3.1. Clay minerals 3.2. Clay mineral semisolid formulations 3.3. Clay/polymer composites and nanocomposites 3.4. Clay minerals in wound dressings 4. Other inorganic materials for wound healing 4.1. Zeolites 4.2. Silica and other silicates 4.3. Other minerals 4.4. Transition metals 5. Conclusion. Conclusion: Inorganic ingredients possess useful features for the development of chronic wounds advanced treatments. They improve physical (mechanical resistance and water vapor transmission), chemical (release of drugs, hemostasis and/or adsorption of exudates and moisture) and biological (antimicrobial effects and improvement of healing) properties of wound dressings. In summary, inorganic ingredients have proved to be a promising and easily accessible products in the treatment of wounds and, more importantly, chronic wounds.

The first inorganic mitogens: Cerium oxide and cerium fluoride nanoparticles stimulate planarian regeneration via neoblastic activation.

We report the first experimental evidence for the mitogenic action of cerium(IV) oxide and cerium(III) fluoride nanoparticles (CONs and CFNs) on the regeneration of a whole organism - freshwater flatworms Schmidtea mediterranea (planarian). Both types of cerium-containing nanoparticles are shown to be a highly potent mitogen for planaria. Both CONs and CFNs, in micro- and nanomolar concentrations, markedly accelerate planarian blastema growth, due to the enhancement of cellular proliferation, causing an increase in the mitotic index and in the quantity of blastema cells in regenerating planaria. CONs provided maximum activity at concentrations which were two orders of magnitude lower than those for CeF3. The valence state of cerium in cerium-containing nanoparticles plays a significant role in the planarian regeneration mechanism: CeO2 nanoparticles containing predominantly Ce4+ species presumably scavenge wound induced reactive oxygen species and moderately activate gene expression processes, while the regenerative action of CeF3 nanoparticles containing only Ce3+ species is manifested in the pronounced expression of the genes involved in cell division, differentiation and migration. This is the first report on the effect of cerium-containing nanoparticles on tissue regeneration in vivo, further revealing the mechanisms of their biological action, which enhances the possibility of their use in cellular technologies.

The Binary Effect on Methicillin-Resistant Staphylococcus aureus of Polymeric Nanovesicles Appended by Proline-Rich Amino Acid Sequences and Inorganic Nanoparticles.

Prevalent research underscores efforts to engineer highly sophisticated nanovesicles that are functionalized to combat antibiotic-resistant bacterial infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA), and that aid with wound healing or immunomodulation. This is especially relevant for patients who are susceptible to Staphylococcus aureus infections postoperatively. Here, antibacterial formulations are incorporated into polymeric, biocompatible vesicles called polymersomes (PsNPs) that self-assemble via hydrophobic interactions of admixed aqueous and organic substances. Nano-PsNPs are synthesized using a high molecular weight amphiphilic block copolymer, and are conjugated to include antimicrobial peptides (AMPs) along the peripheral hydrophilic region and silver nanoparticles (AgNPs) inside their hydrophobic corona. In vitro testing on bacterial and human cell lines indicates that finely tuned treatment concentrations of AMP and AgNPs in PsNPs synergistically inhibits the growth of MRSA without posing significant side effects, as compared with other potent treatment strategies. A ratio of silver-to-AMP of about 1:5.8 corresponding to ≈11.6 µg mL-1 of silver nanoparticles and 14.3 × 10-6 m of the peptide, yields complete MRSA inhibition over a 23 h time frame. This bacteriostatic activity, coupled with nominal cytotoxicity toward native human dermal fibroblast cells, extends the potential for AMP/AgNP polymersome therapies to replace antibiotics in the clinical setting.

Combination of soil organic and inorganic amendments helps plants overcome trace element induced oxidative stress and allows phytostabilisation.

Trace element (TE)-contaminated soils require the improvement of their physico-chemical properties in order to allow their restoration through phytostabilization technologies. This study aimed to determine the usefulness of oxidative stress related parameters to validate the suitability of two different combinations of organic (solid fraction of pig slurry) and inorganic (paper mill sludge or a commercial red mud derivative) amendments for the phytostabilization of an acidic (4.2) TE-contaminated mine soil from SE Spain. Two wild species (Silybum marianum and Piptatherum miliaceum) were greenhouse cultivated and the development of the plants, their ionome, and oxidative stress related parameters were determined. Both amendment combinations increased significantly soil pH (to 5-6) and soil/pore water total organic C and total N concentrations, allowing an adequate plant growth and development (plants did not grow in untreated soils). The combination of amendments significantly reduced metal availability and showed to be effective (specially the one including the red mud derivative) in limiting shoot TE concentrations, which were all within common ranges (exclusion based tolerance of these species). Both protein carbonylation and lipid peroxidation were significantly higher in S. marianum plants from phytostabilized soils than in those from non-contaminated soils, which confirms the oxidative stress these plants suffer despite their satisfactory growth in the treated soils. P. miliaceum plants showed no differences between phytostabilized and non-contaminated soils. Therefore, the combination of amendments and TE-tolerant autochthonous species would be a suitable option for the phytostabilisation of soils contaminated by mining activities, reducing TE solubility and allowing an adequate plant growth.

Combinatorial effects of inorganic ions on adhesion and proliferation of osteoblast-like cells.

Combinatorial effects of three ions, namely silicate (Si), calcium (Ca), and magnesium (Mg) ions, on the adhesion and proliferation of MC3T3-E1 mouse osteoblast-like cells were evaluated. The cells were cultured in single-, dual-, or triple-ion-conditioned culture media with systematically changed ion concentrations. The ranges of Si, Ca, and Mg ion concentrations were set as 10-70, 80-400, and 25-500 ppm, respectively. The numbers of adherent live cells were measured after culturing for 3 h and for 1, 3, and 5 days to examine cell adhesion and proliferation, respectively. Mg ions predominantly enhanced cell adhesion in both the dual-ion (xSi-zMg and yCa-zMg) and triple-ion (xSi-yCa-zMg) systems but had no effect when they acted individually in the single-ion system. Conversely, Si ions predominantly enhanced cell proliferation in most single- and triple-ion-conditioned media. Evaluation of the combinatorial effects of the three ions on cell adhesion and proliferation revealed that the dual- and triple-ion-conditioned media mainly conferred synergistic effects on adhesion but antagonistic effects on proliferation. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1042-1051, 2019.

Dual role of inorganic polyphosphate in cardiac myocytes: The importance of polyP chain length for energy metabolism and mPTP activation.

We have previously demonstrated that inorganic polyphosphate (polyP) is a potent activator of the mitochondrial permeability transition pore (mPTP) in cardiac myocytes. PolyP depletion protected against Ca2+-induced mPTP opening, however it did not prevent and even exacerbated cell death during ischemia-reperfusion (I/R). The central goal of this study was to investigate potential molecular mechanisms underlying these dichotomous effects of polyP on mitochondrial function. We utilized a Langendorff-perfused heart model of I/R to monitor changes in polyP size and chain length at baseline, 20 min no-flow ischemia, and 15 min reperfusion. Freshly isolated cardiac myocytes and mitochondria from C57BL/6J (WT) and cyclophilin D knock-out (CypD KO) mice were used to measure polyP uptake, mPTP activity, mitochondrial membrane potential, respiration and ATP generation. We found that I/R induced a significant decrease in polyP chain length. We, therefore, tested, the ability of synthetic polyPs with different chain length to accumulate in mitochondria and induce mPTP. Both short and long chain polyPs accumulated in mitochondria in oligomycin-sensitive manner implicating potential involvement of mitochondrial ATP synthase in polyP transport. Notably, only short-chain polyP activated mPTP in WT myocytes, and this effect was prevented by mPTP inhibitor cyclosprorin A and absent in CypD KO myocytes. To the contrary, long-chain polyP suppressed mPTP activation, and enhanced ADP-linked respiration and ATP production. Our data indicate that 1) effect of polyP on cardiac function strongly depends on polymer chain length; and 2) short-chain polyPs (as increased in ischemia-reperfusion) induce mPTP and mitochondrial uncoupling, while long-chain polyPs contribute to energy generation and cell metabolism.

Effect of Inorganic Nitrite vs Placebo on Exercise Capacity Among Patients With Heart Failure With Preserved Ejection Fraction: The INDIE-HFpEF Randomized Clinical Trial.

Importance: There are few effective treatments for heart failure with preserved ejection fraction (HFpEF). Short-term administration of inorganic nitrite or nitrate preparations has been shown to enhance nitric oxide signaling, which may improve aerobic capacity in HFpEF. Objective: To determine the effect of 4 weeks' administration of inhaled, nebulized inorganic nitrite on exercise capacity in HFpEF. Design, Setting, and Participants: Multicenter, double-blind, placebo-controlled, 2-treatment, crossover trial of 105 patients with HFpEF. Participants were enrolled from July 22, 2016, to September 12, 2017, at 17 US sites, with final date of follow-up of January 2, 2018. Interventions: Inorganic nitrite or placebo administered via micronebulizer device. During each 6-week phase of the crossover study, participants received no study drug for 2 weeks (baseline/washout) followed by study drug (nitrite or placebo) at 46 mg 3 times a day for 1 week followed by 80 mg 3 times a day for 3 weeks. Main Outcomes and Measures: The primary end point was peak oxygen consumption (mL/kg/min). Secondary end points included daily activity levels assessed by accelerometry, health status as assessed by the Kansas City Cardiomyopathy Questionnaire (score range, 0-100, with higher scores reflecting better quality of life), functional class, cardiac filling pressures assessed by echocardiography, N-terminal fragment of the prohormone brain natriuretic peptide levels, other exercise indices, adverse events, and tolerability. Outcomes were assessed after treatment for 4 weeks. Results: Among 105 patients who were randomized (median age, 68 years; 56% women), 98 (93%) completed the trial. During the nitrite phase, there was no significant difference in mean peak oxygen consumption as compared with the placebo phase (13.5 vs 13.7 mL/kg/min; difference, -0.20 [95% CI, -0.56 to 0.16]; P = .27). There were no significant between-treatment phase differences in daily activity levels (5497 vs 5503 accelerometry units; difference, -15 [95% CI, -264 to 234]; P = .91), Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (62.6 vs 61.9; difference, 1.1 [95% CI, -1.4 to 3.5]; P = .39), functional class (2.5 vs 2.5; difference, 0.1 [95% CI, -0.1 to 0.2]; P = .43), echocardiographic E/e' ratio (16.4 vs 16.6; difference, 0.1 [95% CI, -1.2 to 1.3]; P = .93), or N-terminal fragment of the prohormone brain natriuretic peptide levels (520 vs 533 pg/mL; difference, 11 [95% CI, -53 to 75]; P = .74). Worsening heart failure occurred in 3 participants (2.9%) during the nitrite phase and 8 (7.6%) during the placebo phase. Conclusions and Relevance: Among patients with HFpEF, administration of inhaled inorganic nitrite for 4 weeks, compared with placebo, did not result in significant improvement in exercise capacity. Trial Registration: ClinicalTrials.gov Identifier: NCT02742129.

Grapevine Trunk Diseases: A Review of Fifteen Years of Trials for Their Control with Chemicals and Biocontrol Agents.

Grapevine trunk diseases (GTDs) represent one of the most important problems for viticulture worldwide. Beyond the original causes of this outbreak in some countries like France, the lack of efficient control protocols and the prohibition of using active ingredients such as sodium arsenite and benzimidazoles, until recently used to reduce the impact of some GTDs but deleterious for humans and the environment, have probably worsened the impact of the diseases, leading to increasing economic losses. Since 1990, searches have been made to find efficient tools to control GTDs, testing a wide range of active ingredients and biocontrol agents. This review provides readers with an overview of the results reported in the scientific literature over the last 15 years. In particular, the review focuses on the trials carried out applying chemicals or microorganisms to control Esca complex diseases, Botryosphaeria dieback, and Eutypa dieback, the most widespread GTDs.

Impacts of inorganic anions and natural organic matter on thermally activated persulfate oxidation of BTEX in water.

The present study investigated the impacts of water matrix constituents (CO32-, HCO3-, Cl-, Br-, PO43-, HPO42-, H2PO4-, NO3-, SO42- and natural organic matters (NOM) on the oxidation of a mixture of benzene, toluene, ethylbenzene, and xylenes (BTEX) by thermally activated persulfate (PS). In the absence of matrix constituents, the BTEX oxidation rates decreased in the following order: xylenes > toluene ≈ ethylbenzene > benzene. HCO3-/CO32- and NOM inhibited the BTEX oxidation and the inhibiting effects became more pronounced as the HCO3-/CO32-/NOM concentration increased. SO42-, NO3-, PO43- and H2PO4- did not affect the BTEX oxidation while HPO42- slightly inhibited the reaction. The impacts of Cl- and Br- were complex. Cl- inhibited the benzene oxidation while 100 mM and 500 mM of Cl- promoted the oxidation of m-xylene and p-xylene. Br- completely suppressed the benzene oxidation while 500 mM of Br- strongly promoted the oxidation of xylenes. Detailed explanations on the influence of each matrix constituent were discussed. In addition, various halogenated degradation byproducts were detected in the treatments containing Cl- and Br-. Overall, this study indicates that some matrix constituents such as NOM, HCO3-, CO32-, H2PO4-, Cl- and Br- may reduce the BTEX removal efficiency of sulfate radical-based advanced oxidation process (SR-AOP) and the presence of Cl- and Br- may even lead to the formation of toxic halogenated byproducts.

Membrane interactions and antimicrobial effects of inorganic nanoparticles.

Interactions between nanoparticles and biological membranes are attracting increasing attention in current nanomedicine, and play a key role both for nanotoxicology and for utilizing nanomaterials in diagnostics, drug delivery, functional biomaterials, as well as combinations of these, e.g., in theranostics. In addition, there is considerable current interest in the use of nanomaterials as antimicrobial agents, motivated by increasing resistance development against conventional antibiotics. Here, various nanomaterials offer opportunities for triggered functionalites to combat challenging infections. Although the performance in these diverse applications is governed by a complex interplay between the nanomaterial, the properties of included drugs (if any), and the biological system, nanoparticle-membrane interactions constitute a key initial step and play a key role for the subsequent biological response. In the present overview, the current understanding of inorganic nanomaterials as antimicrobial agents is outlined, with special focus on the interplay between antimicrobial effects and membrane interactions, and how membrane interactions and antimicrobial effects of such materials depend on nanoparticle properties, membrane composition, and external (e.g., light and magnetic) fields.