Several metals belong to a group of non-biodegradable inorganic constituents that, at low concentrations, play fundamental roles as essential micronutrients for the growth and development of plants. However, in high concentrations they can have toxic and/or mutagenic effects, which can be counteracted by natural chemical compounds called chelators. Chelators have a diversity of chemical structures; many are organic acids, including carboxylic acids and cyclic phenolic acids. The exogenous application of such compounds is a non-genetic approach, which is proving to be a successful strategy to reduce damage caused by heavy metal toxicity. In this review, we will present the latest literature on the exogenous addition of both carboxylic acids, including the Kreb’s Cycle intermediates citric and malic acid, as well as oxalic acid, lipoic acid, and phenolic acids (gallic and caffeic acid). The use of two non-traditional organic acids, the phytohormones jasmonic and salicylic acids, is also discussed. We place particular emphasis on physiological and molecular responses, and their impact in increasing heavy metal tolerance, especially in crop species. 相似文献
Methods for the manipulation of single magnetic particles have become very interesting, in particular for in vitro biological studies. Most of these studies require an external microscope to provide the operator with feedback for controlling the particle motion, thus preventing the use of magnetic particles in high‐throughput experiments. In this paper, a simple and compact system with integrated electrical feedback is presented, implementing in the very same device both the manipulation and detection of the transit of single particles. The proposed platform is based on zig‐zag shaped magnetic nanostructures, where transverse magnetic domain walls are pinned at the corners and attract magnetic particles in suspension. By applying suitable external magnetic fields, the domain walls move to the nearest corner, thus causing the step by step displacement of the particles along the nanostructure. The very same structure is also employed for detecting the bead transit. Indeed, the presence of the magnetic particle in suspension over the domain wall affects the depinning field required for its displacement. This characteristic field can be monitored through anisotropic magnetoresistance measurements, thus implementing an integrated electrical feedback of the bead transit. In particular, the individual manipulation and detection of single 1‐μm sized beads is demonstrated. 相似文献
The direct conversion of solar energy into fuels or feedstock is an attractive approach to address increasing demand of renewable energy sources. Photocatalytic systems relying on the direct photoexcitation of metals have been explored to this end, a strategy that exploits the decay of plasmonic resonances into hot carriers. An efficient hot carrier generation and collection requires, ideally, their generation to be enclosed within few tens of nanometers at the metal interface, but it is challenging to achieve this across the broadband solar spectrum. Here the authors demonstrate a new photocatalyst for hydrogen evolution based on metal epsilon‐near‐zero metamaterials. The authors have designed these to achieve broadband strong light confinement at the metal interface across the entire solar spectrum. Using electron energy loss spectroscopy, the authors prove that hot carriers are generated in a broadband fashion within 10 nm in this system. The resulting photocatalyst achieves a hydrogen production rate of 9.5 µmol h?1 cm?2 that exceeds, by a factor of 3.2, that of the best previously reported plasmonic‐based photocatalysts for the dissociation of H2 with 50 h stable operation. 相似文献
Besides their primary role in hemostasis, platelets contain a plethora of immunomodulatory molecules that profoundly affect the entire process of wound repair. Therefore, platelet derivatives, such as platelet-rich plasma or platelet lysate, have been widely employed with promising results in the treatment of chronic wounds. Platelet derivatives provide growth factors, cytokines, and chemokines targeting resident and immigrated cells belonging to the innate and adaptive immune system. The recruitment and activation of neutrophils and macrophages is critical for pathogen clearance in the early phase of wound repair. The inflammatory response begins with the release of cytokines, such as TGF-β, aimed at damping excessive inflammation and promoting the regenerative phase of wound healing. Dysregulation of the immune system during the wound healing process leads to persistent inflammation and delayed healing, which ultimately result in chronic wound. In this review, we summarize the role of the different immune cells involved in wound healing, particularly emphasizing the function of platelet and platelet derivatives in orchestrating the immunological response. 相似文献
This paper presents an optimal bound on the Shannon function L(n,m,) that gives the worstcase circuit-size complexity to approximate, within an approximation degree at least , partial boolean functions having n inputs and domain size m. That is
. Our bound applies to any partial boolean function and any approximation degree, and thus completes the study of boolean function approximation introduced by Pippenger (1977).
Our results give an upper bound for the hardness function h(ƒ), introduced by Nisan and Wigderson (1994), which denotes the minimum value l for which there exists a circuit of size at most l that approximates a boolean function ƒ with degree at least 1/l. Indeed, if H(n) denotes the maximum hardness value achieved by boolean functions with n inputs, we prove that for almost every nH(n)2n/3 + n2 + O(1). The exponent n/3 in the above inequality implies that no family of boolean functions exists which has ‘full’ hardness. This fact establishes connections with Allender and Strauss' (1994) work that explores the structure of BPP.
Finally, we show that for almost every n and for almost every boolean function ƒ of n inputs we have h(ƒ)2n/3−2 logn. The contribution in the proof of the upper bound for L(n, m, ) can be viewed as a set of technical results that globally show how boolean linear operators are ‘well’ distributed on the class of 4-regular domains. This property is then applied to approximate partial boolean functions on general domains using a suitable composition of boolean linear operators. 相似文献
Erythropoietin (Epo) is a crucial hormone regulating red blood cell number and consequently the hematocrit. Epo is mainly produced in the kidney by interstitial fibroblast-like cells. Previously, we have shown that in cultures of the immortalized mouse renal fibroblast-like cell line FAIK F3-5, sphingosine 1-phosphate (S1P), by activating S1P1 and S1P3 receptors, can stabilize hypoxia-inducible factor (HIF)-2α and upregulate Epo mRNA and protein synthesis. In this study, we have addressed the role of intracellular iS1P derived from sphingosine kinases (Sphk) 1 and 2 on Epo synthesis in F3-5 cells and in mouse primary cultures of renal fibroblasts. We show that stable knockdown of Sphk2 in F3-5 cells increases HIF-2α protein and Epo mRNA and protein levels, while Sphk1 knockdown leads to a reduction of hypoxia-stimulated HIF-2α and Epo protein. A similar effect was obtained using primary cultures of renal fibroblasts isolated from wildtype mice, Sphk1−/−, or Sphk2−/− mice. Furthermore, selective Sphk2 inhibitors mimicked the effect of genetic Sphk2 depletion and also upregulated HIF-2α and Epo protein levels. The combined blockade of Sphk1 and Sphk2, using Sphk2−/− renal fibroblasts treated with the Sphk1 inhibitor PF543, resulted in reduced HIF-2α and Epo compared to the untreated Sphk2−/− cells. Exogenous sphingosine (Sph) enhanced HIF-2α and Epo, and this was abolished by the combined treatment with the selective S1P1 and S1P3 antagonists NIBR-0213 and TY52156, suggesting that Sph was taken up by cells and converted to iS1P and exported to then act in an autocrine manner through S1P1 and S1P3. The upregulation of HIF-2α and Epo synthesis by Sphk2 knockdown was confirmed in the human hepatoma cell line Hep3B, which is well-established to upregulate Epo production under hypoxia. In summary, these data show that sphingolipids have diverse effects on Epo synthesis. While accumulation of intracellular Sph reduces Epo synthesis, iS1P will be exported to act through S1P1+3 to enhance Epo synthesis. Furthermore, these data suggest that selective inhibition of Sphk2 is an attractive new option to enhance Epo synthesis and thereby to reduce anemia development in chronic kidney disease. 相似文献
Neuropathy development is a major dose-limiting side effect of anticancer treatments that significantly reduces patient’s quality of life. The inadequate pharmacological approaches for neuropathic pain management warrant the identification of novel therapeutic targets. Mitochondrial dysfunctions that lead to reactive oxygen species (ROS) increase, cytosolic Ca2+ imbalance, and lactate acidosis are implicated in neuropathic pain pathogenesis. It has been observed that in these deregulations, a pivotal role is played by the mitochondrial carbonic anhydrases (CA) VA and VB isoforms. Hence, preclinical studies should be conducted to assess the efficacy of two novel selenides bearing benzenesulfonamide moieties, named 5b and 5d, and able to inhibit CA VA and VB against paclitaxel-induced neurotoxicity in mice. Acute treatment with 5b and 5d (30–100 mg/kg, per os – p.o.) determined a dose-dependent and long-lasting anti-hyperalgesic effect in the Cold plate test. Further, repeated daily treatment for 15 days with 100 mg/kg of both compounds (starting the first day of paclitaxel injection) significantly prevented neuropathic pain development without the onset of tolerance to the anti-hyperalgesic effect. In both experiments, acetazolamide (AAZ, 100 mg/kg, p.o.) used as the reference drug was partially active. Moreover, ex vivo analysis demonstrated the efficacy of 5b and 5d repeated treatments in reducing the maladaptive plasticity that occurs to glia cells in the lumbar portion of the spinal cord and in improving mitochondrial functions in the brain and spinal cord that were strongly impaired by paclitaxel-repeated treatment. In this regard, 5b and 5d ameliorated the metabolic activity, as observed by the increase in citrate synthase activity, and preserved an optimal mitochondrial membrane potential (ΔΨ) value, which appeared depolarized in brains from paclitaxel-treated animals. In conclusion, 5b and 5d have therapeutic and protective effects against paclitaxel-induced neuropathy without tolerance development. Moreover, 5b and 5d reduced glial cell activation and mitochondrial dysfunction in the central nervous system, being a promising candidate for the management of neuropathic pain and neurotoxicity evoked by chemotherapeutic drugs. 相似文献