Trivalent Antimony Research Articles

Antileishmanial activity of Hesperetin on Leishmania donovani, in vitro and in silico inhibition of acetylcholinesterase and investigation of the targets sterol C-24 reductase and N-myristoyltransferase.

The current treatment of leishmaniasis is confronted with significant challenges, including limited efficacy, adverse effects, and parasite resistance to drugs. The search for alternative therapeutic options, including the utilization of natural products, has demonstrated considerable promise. In this study, the antileishmanial activity of the flavonoid hesperetin against Leishmania donovani, the causative agent of visceral leishmaniasis, was reported for the first time. Hesperetin was obtained through the hydrolysis of hesperidin and subsequently subjected to chemical characterisation via Infrared and NMR spectroscopy. The antileishmanial activity and cytotoxicity against RAW 264.7 macrophages were evaluated using the MTT colorimetric assay. In order to investigate the potential mechanisms of action, in vitro acetylcholinesterase inhibition assays and molecular docking analyses were conducted. Hesperetin showed an antipromastigote effect (IC50: 62.89 μM) with no evidence of cytotoxicity (CC50: 612.8 μM), with a selectivity index (SI) of 9.74, being 5.4 times more effective than trivalent antimony. In comparison, antimony showed an IC50 of 80.16 μM, a CC50 of 145.04 μM and a SI of 1.8, indicating a limited safety margin. The compound was observed to inhibit acetylcholinesterase (IC50 of 18.44 μg/mL), present in mitochondrial and plasma membrane of the parasite. Molecular docking and dynamic simulations indicated that hesperetin inhibit sterol C-24 reductase, essential for ergosterol biosynthesis and membrane integrity of L. donovani and shows activity against N-myristoyl transferase, responsible for parasite proliferation cycle. These findings open promising avenues for the development of effective antileishmanial therapies.

Ascorbate peroxidase modulation confirms key role in Leishmania infantum oxidative defence

BackgroundAscorbate peroxidase (APX) has emerged as a promising target for chemotherapy because of its absence in humans and crucial role in the antioxidant defence of trypanosomatids. APXs, which are class I haeme-containing enzymes, reduces hydrogen peroxide using ascorbate to produce water and monodehydroascorbate, thereby preventing cell damage caused by H2O2.MethodsWe aimed to create an APX-knockout L. infantum line using CRISPR/Cas9. Despite unsuccessful attempts at full knockouts, we achieved deletion of chromosomal copies post-APX episomal insertion, yielding LiΔchrAPX::LbAPX parasites. We performed phenotypic characterization to assess the impact of these genetic modifications, which included the determination of APX transcript expression levels using quantitative PCR, drug sensitivity, infectivity, and parasite survival in macrophages.ResultsQuantitative polymerase chain reaction (PCR) analysis revealed a 10- to 13-fold reduction in APX transcript expression in LiΔchrAPX::LbAPX compared with wild-type (LiWT) and APX-overexpressing (Li::Cas9::LbAPX) parasites, respectively. The episomes in those knockdown parasites remained stable even after 20 drug-free passages in vitro. Li::Cas9::LbAPX parasites showed increased resistance to trivalent antimony (SbIII) and isoniazid, reduced tolerance to H2O2, and unchanged macrophage infectivity compared with LiWT. In contrast, LiΔchrAPX::LbAPX parasites were more sensitive to SbIII and isoniazid, exhibited greater susceptibility to H2O2-induced oxidative stress, and 72 h post-infection, showed fewer infected macrophages and intracellular amastigotes compared with LiWT parasites.ConclusionsOur findings hint at the indispensability of APX in L. infantum and raise the possibility of its potential as a therapeutic target for leishmaniasis.Graphical

Mechanisms and valorization of selective adsorption of Sb(III) by amino-functionalized lignin-based porous biochar

Antimony contamination in aquatic environment raises tremendous concerns for human health and ecosystem safety, while there is a lack of methods for efficient and selective adsorption of antimony. In this study, an adsorbent for trivalent antimony (Sb(III)) removal is obtained by cross-linking polyethyleneimine (PEI) onto phosphoric acid-modified lignin-based porous biochar (PPLB). PPLB exhibits efficient adsorption of Sb(III) with a maximum value of 371.7 mg/g, which is also highly selective as the Sb(III) removal capability by PPLB remains unaffected under the common co-existing anions (Cl-, NO3–, PO43-, and CO32–) and less affected with the co-existing cations (Cd2+, Zn2+, Cu2+, and Pb2+). Such a performance is validated in three simulated Sb(III)-contaminated water bodies (Zijiang River water, industrial wastewater, and mining area water). Understanding of the adsorption mechanisms is further established via density functional theory calculations, revealing the dominant adsorption site of Sb(III) on PPLB is –NH- groups. It’s finally concluded that the removal of Sb(III) by PPLB is governed by complexation, with also the contribution from ligand exchange and hydrogen bonding. As a proof of concept, the spent PPLB adsorbed with Sb(III) is valorized into an active material of sodium ion battery, demonstrating a specific capacity of 192.4 mA h/g for 1000 cycles with a good long-term stability.

Long-Chain Molecular Crystals Antimony(III) Alkanethiolates Sb(SCnH2n+1)3 (n ≥ 12): Synthesis, Crystal and Electronic Structures, and Supramolecular Self-Assembly via Secondary Interactions.

Currently, there is not much success in solving the molecular and crystal structures of long-chain metal alkanethiolate complexes [M(SCnH2n+1)m] at the atomic level. Taking Sb(SC16H33)3 (1) as an example, we herein disclose the structural characteristics of long-chain trivalent antimony(III) alkanethiolates Sb(SCnH2n+1)3 (n ≥ 12) by single-crystal X-ray crystallography. Specifically, the Sb atom is three-coordinated by alkanethiolate ligands and a slightly distorted triangular pyramid SbS3 core is formed owing to the unique intramolecular stereochemistry of three alkyl chains, namely, two of them almost parallel aligning and the third chain extending alone around the SbS3 core. We further determine the conformation, spatial orientation and packing density of alkyl chains in 1 along with a comparison to those in other long-chain crystalline systems, and reveal the roles of intermolecular van der Waals and Sb···S secondary interactions in molecular self-assembly, which enables 1 to be a layer-structured molecular crystal with a monoclinic P21/c unit cell. The band structures and the atomic orbital contributions to the valence band maximum and conduction band minimum for 1 have also been evaluated by DFT calculations and rationally correlated with its optical absorption property. This study will help understand and discover new structures and structure-property relations of long-chain chemical systems.

Deletion of the lipid droplet protein kinase gene affects lipid droplets biogenesis, parasite infectivity, and resistance to trivalent antimony in Leishmania infantum.

The Lipid Droplet Protein Kinase (LDK) facilitates lipid droplet (LD) biogenesis, organelles involved in various metabolic and signaling functions in trypanosomatids. As LDK's function has not been previously explored in Leishmania spp., we utilized CRISPR/Cas9 technology to generate LDK-knockout lines of Leishmania infantum to investigate its role in this parasite. Our findings demonstrate that LDK is not an essential gene for L. infantum, as its deletion did not impede parasite survival. Furthermore, removing LDK did not impact the growth of promastigote forms of L. infantum lacking LDK. However, a noticeable reduction in LDs occurred during the stationary phase of parasite growth following LDK deletion. In the presence of myriocin, a LD inducer, LDK-knockout parasites displayed reduced LD abundance during both logarithmic and stationary growth phases compared to control parasites. Moreover, an infection analysis involving THP-1 cells revealed that 72 h post-infection, LDK-knockout L. infantum lines exhibited fewer infected macrophages and intracellular amastigotes than control parasites. LDK-knockout L. infantum lines also displayed 1.7 to 1.8 -fold greater resistance to trivalent antimony than control parasites. There were no observed alterations in susceptibility to amphotericin B, miltefosine, or menadione in LDK-knockout L. infantum lines. Our results suggest that LDK plays a crucial role in the biogenesis and/or maintenance of LDs in L. infantum, as well as in parasite infectivity and resistance to trivalent antimony.

Anti-Leishmania compounds can be screened using Leishmania spp. expressing red fluorescence (tdTomato).

The main challenges associated with leishmaniasis chemotherapy are drug toxicity, the possible emergence of resistant parasites, and a limited choice of therapeutic agents. Therefore, new drugs and assays to screen and detect novel active compounds against leishmaniasis are urgently needed. We thus validated Leishmania braziliensis (Lb) and Leishmania infantum (Li) that constitutively express the tandem tomato red fluorescent protein (tdTomato) as a model for large-scale screens of anti-Leishmania compounds. Confocal microscopy of Lb and Li::tdTomato revealed red fluorescence distributed throughout the entire parasite, including the flagellum, and flow cytometry confirmed that the parasites emitted intense fluorescence. We evaluated the infectivity of cloned promastigotes and amastigotes constitutively expressing tdTomato, their growth profiles in THP-1 macrophages, and susceptibility to trivalent antimony, amphotericin, and miltefosine in vitro. The phenotypes of mutant and wild-type parasites were similar, indicating that the constitutive expression of tdTomato did not interfere with the evaluated parameters. We applied our validated model to a repositioning strategy and assessed the susceptibility of the parasites to eight commercially available drugs. We also screened 32 natural plant and fungal extracts and 10 pure substances to reveal new active compounds. The infectivity and Glucantime treatment efficacy of BALB/c mice and golden hamsters infected with Lb and Li::tdTomato mutant lines, respectively, were very similar compared to animals infected with wild-type parasites. Standardizing our methodology would offer more rapid, less expensive, and easier assays to screen of compounds against L. braziliensis and L. infantum in vitro and in vivo. Our method could also enhance the discovery of active compounds for treating leishmaniasis.

Excitation Wavelength‐Dependent Fluorescence of a Lanthanide Organic Metal Halide Cluster for Anti‐Counterfeiting Applications

AbstractThe achievement of significant photoluminescence (PL) in lanthanide ions (Ln3+) has primarily relied on host sensitization, where energy is transferred from the excited host material to the Ln3+ ions. However, this luminous mechanism involves only one optical antenna, namely the host material, which limits the accessibility of excitation wavelength‐dependent (Ex‐De) PL. Consequently, the wider application of Ln3+ ions in light‐emitting devices is hindered. In this study, we present an organic–inorganic compound, (DMA)4LnCl7 (DMA+=[CH3NH2CH3]+, Ln3+=Ce3+, Tb3+), which serves as an independent host lattice material for efficient Ex‐De emission by doping it with trivalent antimony (Sb3+). The pristine (DMA)4LnCl7 compounds exhibit high luminescence, maintaining the characteristic sharp emission bands of Ln3+ and demonstrating a high PL quantum yield of 90–100 %. Upon Sb3+ doping, the compound exhibits noticeable Ex‐De emission with switchable colors. Through a detailed spectral study, we observe that the prominent energy transfer process observed in traditional host‐sensitized systems is absent in these materials. Instead, they exhibit two independent emission centers from Ln3+ and Sb3+, each displaying distinct features in luminous color and radiative lifetime. These findings open up new possibilities for designing Ex‐De emitters based on Ln3+ ions.

Enhanced adsorption for trivalent antimony by nano-zero-valent iron-loaded biochar: performance, mechanism, and sustainability.

The discharge of tailing leachate and metallurgical wastewater has led to an increasing trend of water pollution. In this study, nZVI-modified low-temperature biochar was used to adsorb Sb(III) from water. The adsorption capacity and speed of nZVI-BC were better than those of BC, and the best adsorption effect was observed for 4nZVI-BC, with 93.60mg·g-1 maximum adsorptive capacity, which was 208.61% higher than the original BC. The Langmuir and Temkin models were well fitted (R2 ≥ 0.99), and PSO was more in line with the 4nZVI-BC adsorption process, indicating that the adsorption was a monolayer physico-chemical adsorption. The combination of XRD, FTIR, and XPS characterization demonstrated that the adsorption mechanism predominantly included redox reactions, complexation, and electrostatic interactions. The thermodynamic results demonstrated that 4nZVI-BC adsorption on Sb(III) was a spontaneous endothermic process. Additionally, the order of the influence of interfering ions on 4nZVI-BC was CO32- > H2PO4- > SO42- > Cl-. After three repeated uses and adsorption-desorption, the adsorption ratio of Sb(III) by 4nZVI-BC was still as high as 90% and 65%, respectively. This study provides a theoretical reference for the exploration and development of Sb(III) removal technologies for aquatic environments.

Coupled sorptive and oxidative antimony(III) removal by iron-modified biochar: Mechanisms of electron-donating capacity and reactive Fe species

Sorption and oxidation are two potential pathways for the decontamination of trivalent antimony (Sb(III))-bearing water, using iron (Fe)-modified biochar (FeBC). Here we investigated the sorption and oxidation behavior of FeBC for Sb(III) in aqueous solutions. Results revealed that Sb(III) removal by FeBC was significantly improved showing the maximum Sb(III) sorption (64.0 mg g−1). Density functional theory (DFT) calculations indicated that magnetite (Fe3O4) in FeBC offered a sorption energy of −0.22 eV, which is 5 times that of non-modified biochar. With the addition of peroxymonosulfate (PMS), the sorption of Sb(III) on FeBC was 7 times higher than that on BC, indicating the sorption capacity of FeBC for Sb(III) could be substantially increased by adding oxidizing agents. Electrochemical analysis showed that Fe modification imparted FeBC higher electron-donating capacity than that of BC (0.045 v. s. 0.023 mmol e− (g biochar)−1), which might be the reason for the strong Sb(III) oxidation (63.6%) on the surface of FeBC. This study provides new information that is key for the development of effective biochar-based composite materials for the removal of Sb(III) from drinking water and wastewater. The findings from this study have important implications for protecting human health and agriculture.

Distribution, metabolism, and toxicity of antimony species in wistar rats. A bio-analytical approach

This work studied the distribution, reactivity, and biological effects of pentavalent or trivalent antimony (Sb(V), Sb(III)) and N-methylglucamine antimonate (NMG-Sb(V)) in Wistar Rats. The expression of fibrosis genes such as α − SMA, PAI-1, and CTGF were determined in Liver, and Kidney tissues. Wistar rats were treated with different concentrations of Sb(V), Sb(III), As(V) and As(III), and MA via intra-peritoneal injections. The results indicated a noteworthy elevation in mRNA levels of plasminogen activator 1 (PAI-1) in the kidneys of rats that were injected. The main accumulation site for Sb(V) was observed to be the liver, from which it is primarily excreted in its reduced form (Sb(III)) through the urine. The generation of Sb(III) in the kidneys has been found to induce damage through the expression of α-SMA and CTGF, and also lead to a higher creatinine clearance compared to As(III).

Assessing the effect of antimony pressure on trypanothione reductase activity in Leishmania (Viannia) braziliensis

Leishmania parasites have an oxidative and chemical defense mechanism called trypanothione system (T[SH]2), the most abundant thiol system in trypanosomatids. This system has a central role in processing pentavalent antimony and resistance has been related to a better capacity to metabolize it through the activation of T[SH]2 enzymatic cascade. A biochemical approach was applied to assess the effect of trivalent (SbIII) and pentavalent antimony (SbV) on Trypanothione Reductase (TR) activity of two Leishmania (Viannia) braziliensis clinical isolates, which were labeled as responder (R) and non-responder (NR) after patient treatment with Glucantime®. Both isolates were characterized based on in vitro susceptibility to SbIII and SbV and trypanothione reductase (TR) activity. SbIII and SbV discriminated susceptibility profiles in all parasite forms, since isolate NR had significantly higher EC50 values than isolate R. Differences were observed in TR activity between promastigotes, axenic amastigotes and intracellular amastigotes: R (0.439 ± 0.009, 0.103 ± 0.01 and 0.185 ± 0.01AU.min−1.μg of protein−1) and NR (1.083 ± 0.04, 0.914 ± 0.04 and 0.343 ± 0.04 AU. min−1.μg of protein−1), respectively. Incubation with SbIII and SbV using each form EC50 value caused a time-dependent differential effect on TR activity suggesting that oxidative defense is related to the antimony susceptibility phenotype. Data gathered here shows a biochemical approach able to discriminate two L. (V.) braziliensis clinical isolates measurements TR activity of promastigotes, axenic amastigotes and intracellular amastigotes.

Identification of Leishmania infantum Epidemiology, Drug Resistance and Pathogenicity Biomarkers with Nanopore Sequencing.

The emergence of drug-resistant strains of the parasite Leishmania infantum infecting dogs and humans represents an increasing threat. L. infantum genomes are complex and unstable with extensive structural variations, ranging from aneuploidies to multiple copy number variations (CNVs). These CNVs have recently been validated as biomarkers of Leishmania concerning virulence, tissue tropism, and drug resistance. As a proof-of-concept to develop a novel diagnosis platform (LeishGenApp), four L. infantum samples from humans and dogs were nanopore sequenced. Samples were epidemiologically typed within the Mediterranean L. infantum group, identifying members of the JCP5 and non-JCP5 subgroups, using the conserved region (CR) of the maxicircle kinetoplast. Aneuploidies were frequent and heterogenous between samples, yet only chromosome 31 tetrasomy was common between all the samples. A high frequency of aneuploidies was observed for samples with long passage history (MHOM/TN/80/IPT-1), whereas fewer were detected for samples maintained in vivo (MCRI/ES/2006/CATB033). Twenty-two genes were studied to generate a genetic pharmacoresistance profile against miltefosine, allopurinol, trivalent antimonials, amphotericin, and paromomycin. MHOM/TN/80/IPT-1 and MCRI/ES/2006/CATB033 displayed a genetic profile with potential resistance against miltefosine and allopurinol. Meanwhile, MHOM/ES/2016/CATB101 and LCAN/ES/2020/CATB102 were identified as potentially resistant against paromomycin. All four samples displayed a genetic profile for resistance against trivalent antimonials. Overall, this proof-of-concept revealed the potential of nanopore sequencing and LeishGenApp for the determination of epidemiological, drug resistance, and pathogenicity biomarkers in L. infantum.

Exploring the role of extracellular polymeric substances in the antimony leaching of tailings by Acidithiobacillus ferrooxidans.

The concentration of Sb bearing tailings in water located in abandoned antimony mines was found to be a big problem, as they contaminate other water resources and entire food chain. Microorganisms were found to be key in tailing leaching and reaction speeding in the presence of extracellular polymeric substances (EPS) produced by bacteria. Herein, we investigated the pattern of the Sb leaching from Sb bearing tailings using Acidithiobacillus ferrooxidans, and analyzed the mechanism of EPS in the leaching process of Sb. To completely and deeply understand the functions of EPS in the bioleaching of antimony tailings, the generation behavior of EPS produced by Acidithiobacillus ferrooxidans (A. ferrooxidans) during bioleaching was characterized by three-dimensional excitation-emission matrix (3D-EEM). Meanwhile, X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FT-IR) were used to show the changes of EPS functional groups before and after leaching. Compared with the functional groups in EPS produced by A. ferrooxidans before leaching, the content of hydroxyl and amino groups that reduce high-valent metals to low-valent metals in EPS decreases after leaching, and the carbonyl content increases, corresponding to the ratio of trivalent antimony increased, indicating that EPS could reduce the risk of pentavalent antimony to trivalent one. At the same time, with biological scanning electron microscopy and energy spectrum scanning, the observation of EPS on the mineral surface showed that Sb was adsorbed in the EPS, and the XPS of Sb was fine. Spectral analysis showed that the Sb adsorbed in EPS contained both Sb(III) and Sb(V). Besides, for revealing the influence of EPS in the leaching process of Sb from tailings, this work provided an in-depth understanding of the mechanism of Sb released from tailings under the action of A. ferrooxidans and further provides a basis for the biogeochemical cycle of Sb.

Realization of p-type In1.75Sb0.25Se3 alloys for short-wave infrared photodetectors

The narrow-gap semiconductors (NGSs) with two-dimensional (2D) layered structures provide fundamental advantages, such as low noise and high quantum efficiency, for short-wave infrared (SWIR) optoelectronic devices. However, realizing high-performance photodetectors based on 2D NGSs with high photoresponsivity, low noise, and fast response speed remains a challenge. Here, we present the design, preparation, and characterization of an In2(1−x)Sb2xSe3 SWIR photodetector. Trivalent antimony (Sb3+) substitutional doping not only induced the β′-β phase transition at room temperature but also made the alloy a good candidate for the p-type semiconductor. Moreover, the individual In1.75Sb0.25Se3 nanoflake realized an excellent photoresponse in a broadband range from visible (405 nm) to SWIR (1550 nm) light with a photoresponsivity of 134 A W−1 and a detectivity of 1.82 × 107 Jones. These performances were superior to the reported In2Se3, Sb2Se3, and other In or Sb selenide photodetectors, which indicated that the β-In2(1−x)Sb2xSe3 alloy may provide a potential building block for short-wave infrared photodetectors.

Graphene oxide supported sulfidated nano zero-valent iron (S-nZVI@GO) for antimony removal: The role of active oxygen species and reaction mechanism

Sulfidated nano zero-valent iron (S-nZVI) was used to remove various pollutants from wastewater. However, the instability, poor dispersibility, and low electron transfer efficiency of S-nZVI limit its application. Herein, graphene oxide supported sulfidated nano zero-valent iron (S-nZVI@GO) was successfully synthesized using graphene oxide (GO) as a carrier. The properties of S-nZVI@GO were characterized by scanning electron microscopy coupled to X-ray photoelectron spectroscopy (SEM-EDS), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS) concerning the surface morphology, crystalline structure, and elemental components. S-nZVI@GO displayed an excellent capacity for antimony (Sb) removal under aerobic conditions (96.7%), with a high adsorption capacity (Qmax = 311.75 mg/g). It maintained a high removal rate (over 90%) during a wide pH range (3–9). More importantly, S-nZVI@GO activated the molecular oxygen in water via a single-electron pathway to produce •O2－ and H2O2, and then oxidized trivalent antimony (Sb(III)) to pentavalent antimony (Sb(V)) and further separated it by synergistic adsorption and co-precipitation. Therefore, S-nZVI@GO shows excellent potential for Sb contamination remediation.

Optimisation of preparation conditions and removal mechanism for trivalent antimony by biochar-supported nano zero-valent iron

In this study, the preparation conditions of nano zero-valent iron biochar (nZVI-BC)​ was optimised with the aim of removing Sb(III) from aqueous solutions. Among all the prepared nZVI-BC, 5-1nZVI-BC (98.25 mg/g) and 7-4nZVI-BC (91.26 mg/g) were considered to be more efficient adsorbents for Sb(III) adsorption, and their adsorption capacity increased by 457% and 157%, respectively, than that of pristine BC. Both the Langmuir and Freundlich models were well fitted (R 2 ≥ 0.92), indicating that the adsorption process occurred through the synergistic effects of monolayer adsorption and multilayer adsorption. With the increase in the ratio of biochar to iron, the second-order kinetics could better describe the adsorption behaviour, which was controlled by chemisorption. Investigation of the adsorption mechanism using X-ray photoelectron spectroscopy (XPS) and kinetic modelling showed that there were two adsorption behaviours for Sb(III): (i) Sb(V) from the oxidisation of Sb(III) or Sb(III) combined with the functional groups on the surface of nZVI-BC to form antimonite/antimonate, which was attached to biochar surface to remove Sb(III). (ii) Negatively charged Sb(III)/Sb(V) combined with Fe(II)/Fe(III) to form precipitates, such as FeSb 2 O 4 and FeSbO 4 , that were attached to the biochar surface, resulting in removing of Sb(III). Moreover, the reusability and recyclability of the screened nZVI-BC samples were tested in this study. The removal rate for Sb(III) remained approximately 75% after three reuses and 50%–80% through adsorption/desorption after two cycles. These results show that the screened nZVI-BC has a promising prospect as an economical and efficient adsorbent for Sb(III) removal from wastewater. • nZVI-BC adsorbed Sb(III) more rapidly and at higher amounts than BC. • 5-1nZVI-BC was considered as the optimal adsorbent for Sb(III) removal. • Adsorption occurred by synergistic effects of monolayer and multilayer adsorption. • Redox and precipitation reaction are the removal mechanism of Sb(III) by nZVI-BC.

Biochar microtube interconnected hydrotalcite nanosheets for the adsorption of aqueous Sb(III)

Actuated by the non-ionic heavy metal of antimony (Sb) contaminants with undesired toxicity to the environment and human health, capturing Sb is urgent to remedy contaminated water. Herein, the lamellar MnCo hydrotalcite was grown on catkin-derived biochar through the in situ etching of ZIF-L to construct a hierarchical microtube@nanosheet hybrid (CLMH) for Sb immobilization. The adsorption behaviour and mechanism of trivalent antimony (Sb (III)) on the CLMH were investigated. The CLMH shows good pH applicability for capturing Sb(III) at pH from 2 to 9. The excellent adsorption capacity of CLMH for Sb(III) is 247.62 mg g−1 at 303 K, and the endothermic process is proved by the positive value of Δ (10.54 kJ mol−1). The adsorption process is fitted with the intra-particle diffusion model, which can be described with external mass transfer, intraparticle diffusion in pores, and equilibrium stage. The adsorption mechanism is proved, which includes the bind of Metal–O–Sb bonds by inner-sphere complex, the embedding of Sb in the intercalation of hydrotalcite, redox between Mn and Sb, and functional groups dependent anchoring effect. The work benefits the understanding of the antimony removal behaviour over the hierarchical microtube@nanosheet hybrids.

Involvement of tryparedoxin peroxidase (TryP) and trypanothione reductase (TryR) in antimony unresponsive of Leishmania tropica clinical isolates of Iran

Clinical resistance to pentavalent antimonial compounds has long been recognized as a major problem in the treatment of human leishmaniasis. Trypanothione metabolism, the main form of thiol, has shown to play a central role in antimony resistance of laboratory-generated resistant Leishmania spp. and field-isolated resistant L. donovani; but the mechanism of antimony resistance in the clinical isolates of L. tropica causing anthroponotic cutaneous leishmaniasis (ACL) is less studied. Patients were selected among confirmed positive ACL cases who referred to Pasteur Institute of Iran, Tehran, from endemic regions of north-east and south of Iran. L. tropica clinical isolates were collected from patients who were either treatment-responsive (MAS=S1 to S5) or unresponsive (MAR=R1 to R4) to Glucantime® (meglumine antimoniate=MA). Isolates were tested for sensitivity to trivalent antimony (SbIII) in promastigotes and to pentavalent antimony (SbV) in intracellular amastigotes stages. Intracellular thiol levels were assayed and trypanothione-dependent components, including trypanothione reductase (TR) and tryparedoxin peroxidase I (TryP) were analysed at protein level and enzymatic activity in isolates. The MAR isolates had an approximate two fold increase in the levels of intracellular thiols (P< 0.05) accompanied by an average 5-10 fold increase in in vitro resistance to antimony. TryP was amplified at the protein level in all MAR strains as compared to the MAS strains (range: 2.8-5.6 fold). All MAR isolates metabolized H2O2 at higher rates than MAS isolates (8.55±0.75 nmol/min/mg vs. 3.14±0.36 nmol/min/mg) (P< 0.05). In addition, levels of TryR protein were also markedly elevated in 3 out of 4 MAR isolates (range: 2.2-4.1 fold). This was accompanied by overexpressed TryR activity (mean level of 46.83±2.43 for extracts of MAR vs. 20.98±3.02 for MAS strains) (P< 0.05).Elevated levels of TryP, active enzyme in peroxide detoxification, were observed in MAR parasites resulting in an increased metabolism of H2O2. TryR activity was overexpressed on average in extracts of MAR strains, but not in all isolates. Enhanced anti-oxidant defenses through thiol metabolism may play a significant role in clinical resistance of ACL patients to Glucantime.

Trivalent antimony removal using carbonaceous nanomaterial loaded with zero-valent bimetal (iron/copper) and their effect on seed growth

As rapid industrial and social growth, antimony mines are the overexploited, leading to the accumulation of trivalent antimony in the aquatic environment near smelters, which harm human health. To eradicate trivalent antimony from water, an innovative nanomaterial in the form of sludge biochar loaded with zero-valent bimetal was synthesized using a liquid-phase reduction method. The adsorption performance of the nanomaterial for trivalent antimony was investigated based on a series of adsorption experiments using sludge biochar, nano zero-valent iron biochar, and nano zero-valent bimetal biochar. The results showed that the optimal adsorption performance of the three nanomaterials for trivalent antimony, considering the economic practicability, was highlighted at solution pH of 3 and 0.05 g of nanomaterial. Additionally, the maximum adsorption capacity of sludge biochar, nano zero-valent iron biochar, and nano zero-valent bimetal biochar is 3.89 mg g−1 at 35 °C, 32.01 mg g−1 at 25 °C, 50.96 mg g−1 at 25 °C, respectively. The adsorption process of sludge biochar is endothermic, resulting in an increase in the adsorption capacity with increasing temperature, whereas the exothermic reaction contributes to decrease in the adsorption capacity at increasing temperature for the other two carbon nanomaterials. The inhibitory effect of coexisting ions was in the order: Al3+ > NH4+ > Na+ > K+; CO32− > CH3COO− > H2PO4− > S2−. Additionally, nanomaterials promoted seed germination and growth. Investigation of the adsorption mechanism using X-ray photoelectron spectroscopy showed that trivalent antimony was oxidised to pentavalent antimony, and Fe(III) was reduced to Fe(II). The formed primary battery formed by copper ions and iron acclerated electron transfer and improved the adsorption rate. This implied that trivalent antimony could be removed through the synergistic action of the adsorption behaviour and redox reaction. Therefore, the biochar loaded with the zero-valent bimetal serves as a pathway for eradicating trivalent antimony.

Simvastatin Resistance of Leishmania amazonensis Induces Sterol Remodeling and Cross-Resistance to Sterol Pathway and Serine Protease Inhibitors.

The sterol biosynthesis pathway of Leishmania spp. is used as a pharmacological target; however, available information about the mechanisms of the regulation and remodeling of sterol-related genes is scarce. The present study investigated compensatory mechanisms of the sterol biosynthesis pathway using an inhibitor of HMG-CoA reductase (simvastatin) and by developing drug-resistant parasites to evaluate the impact on sterol remodeling, cross-resistance, and gene expression. Simvastatin-resistant L. amazonensis parasites (LaSimR) underwent reprogramming of sterol metabolism manifested as an increase in cholestane- and stigmastane-based sterols and a decrease in ergostane-based sterols. The levels of the transcripts of sterol 24-C-methyltransferase (SMT), sterol C14-α-demethylase (C14DM), and protease subtilisin (SUB) were increased in LaSimR. LaSimR was cross-resistance to ketoconazole (a C14DM inhibitor) and remained sensitive to terbinafine (an inhibitor of squalene monooxygenase). Sensitivity of the LaSimR mutant to other antileishmanial drugs unrelated to the sterol biosynthesis pathway, such as trivalent antimony and pentamidine, was similar to that of the wild-type strain; however, LaSimR was cross-resistant to miltefosine, general serine protease inhibitor N-p-tosyl-l-phenylalanine chloromethyl ketone (TPCK), subtilisin-specific inhibitor 4-[(diethylamino)methyl]-N-[2-(2-methoxyphenyl)ethyl]-N-(3R)-3-pyrrolidinyl-benzamide dihydrochloride (PF-429242), and tunicamycin. The findings on the regulation of the sterol pathway can support the development of drugs and protease inhibitors targeting this route in parasites.