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Ca2+ signaling is central to plant development and acclimation. While Ca2+-responsive proteins have been investigated intensely in plants, only a few Ca2+-permeable channels have been identified, and our understanding of how intracellular Ca2+ fluxes is facilitated remains limited. Arabidopsis thaliana homologs of the mammalian channel-forming mitochondrial calcium uniporter (MCU) protein showed Ca2+ transport activity in vitro. Yet, the evolutionary complexity of MCU proteins, as well as reports about alternative systems and unperturbed mitochondrial Ca2+ uptake in knockout lines of MCU genes, leave critical questions about the in vivo functions of the MCU protein family in plants unanswered. Here, we demonstrate that MCU proteins mediate mitochondrial Ca2+ transport in planta and that this mechanism is the major route for fast Ca2+ uptake. Guided by the subcellular localization, expression, and conservation of MCU proteins, we generated an mcu triple knockout line. Using Ca2+ imaging in living root tips and the stimulation of Ca2+ transients of different amplitudes, we demonstrated that mitochondrial Ca2+ uptake became limiting in the triple mutant. The drastic cell physiological phenotype of impaired subcellular Ca2+ transport coincided with deregulated jasmonic acid-related signaling and thigmomorphogenesis. Our findings establish MCUs as a major mitochondrial Ca2+ entry route in planta and link mitochondrial Ca2+ transport with phytohormone signaling. Monitoring of subcellular Ca2+ dynamics in living Arabidopsis roots reveals that MCU proteins provide the dominant mitochondrial Ca2+ uptake mechanism in vivo.

A series of nine different mono and bimetallic catalysts based on Ni, Rh and Pd supported on γ-Al2O3 or CeO2-Al2O3 was screened and compared in terms of activity and stability for the dry reforming of methane (DRM) reaction. All catalysts were prepared by the incipient wetness impregnation (IWI) method and characterized by XRD, XRF, TPR, H2 chemisorption and N2 physisorption. The used techniques aimed at determining crystalline phases, metal loading and dispersion and textural properties, which are properties that will affect the catalytic performance. The reactions were carried out in a fixed bed quartz reactor with temperatures ranging from 700° to 800 °C, WHSV 30 L gcat−1 h−1 and CH4:CO2 = 1 for periods of at least 48 h. All monometallic Ni based catalyst suffered from deactivation by coke deposition in the first hours of reaction at 700 °C. However, the original catalytic performance of these catalysts was restored after a regeneration treatment. At higher temperatures (800 °C), the 15%Ni/CeO2-Al2O3 catalyst presented no obvious signs of deactivation over the course of 48 h. Monometallic Pd/CeO2-Al2O3 catalysts, despite presenting higher turnover frequencies (TOF) when compared to monometallic and bimetallic Ni based catalysts, lost activity due to coke deposition. Both monometallic Rh based catalysts (0.5%Rh/CeO2-Al2O3 and 1%Rh/CeO2-Al2O3) presented a remarkable activity and stability with no signs of deactivation for 96 h TOS. The 0.5%Rh/CeO2-Al2O3 catalyst presented the highest TOF values among all screened catalyst with TOFCH4 of 9.9 s−1 and TOFCO2 of 12 s−1.

Brazilian plant biodiversity is a rich alternative source of bioactive compounds since plant-derived extracts and/or their secondary metabolites exhibit potential properties to treat several diseases. In this context, Licania rigida Benth (Chrysobalanaceae Family), a large evergreen tree distributed in Brazilian semi-arid regions, deserves attention for its widespread use in popular medicine, although its biological properties are still poorly studied. The aim of this study was to examine (1) acute and sub-chronic oral toxicity at 2000 mg/kg dose; (2) in vitro cytotoxicity at 0.1; 1; 10; 100 or 1000 µg/ml; (3) in vivo mutagenicity at 5, 10 or 20 mg/ml, and (4) potential antioxidant protective effect of L. rigida aqueous leaf extract of (AELr). No marked apparent toxic and genotoxic effects were observed using in vitro and in vivo assays after in vitro treatment of Chinese hamster ovary cell line (CHO-K1) with AELr or in vivo exposure of Wistar rats and Drosophila melanogaster to different extract concentrations. Concerning the antioxidant effect, the extract exhibited a protective effect by decreasing lipid peroxidation as determined by malondialdehyde levels. No significant changes were observed for glutathione (GSH) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Data demonstrate the beneficial potential of AELr to be employed for therapeutic purposes. However, further studies are required to validate the pharmacological application of this plant extract to develop as a phytotherapeutic formulation.

Ouabain is a classic Na+K+ATPase ligand and it has been described to have neuroprotective effects on neurons and glial cells at nanomolar concentrations. In the present work, the neuroprotective and immunomodulatory potential of ouabain was evaluated in neonatal rat retinal cells using an optic nerve axotomy model in vitro. After axotomy, cultured retinal cells were treated with ouabain (3 nM) at different periods. The levels of important inflammatory receptors in the retina such as TNFR1/2, TLR4, and CD14 were analyzed. We observed that TNFR1, TLR4, and CD14 were decreased in all tested periods (15 min, 45 min, 24 h, and 48 h). On the other hand, TNFR2 was increased after 24 h, suggesting an anti-inflammatory potential for ouabain. Moreover, we showed that ouabain also decreased Iba-1 (microglial marker) density. Subsequently, analyses of retrograde labeling of retinal ganglion cells (RGC) were performed after 48 h and showed that ouabain-induced RGC survival depends on autophagy. Using an autophagy inhibitor (3-methyladenine), we observed a complete blockage of the ouabain effect. Western blot analyses showed that ouabain increases the levels of autophagy proteins (LC3 and Beclin-1) coupled to p-CREB transcription factor and leads to autophagosome formation. Additionally, we found that the ratio of cleaved/pro-caspase-3 did not change after ouabain treatment; however, p-JNK density was enhanced. Also, ouabain decreased reactive oxygen species production immediately after axotomy. Taken together, our results suggest that ouabain controls neuroinflammation in the retina following optic nerve axotomy and promotes RGC neuroprotection through activation of the autophagy pathway.

One of the physiologic mechanisms responsible to maintain asymmetric phospholipid distribution (in particular phosphatidylserine, PS) in human erythrocyte membranes is orchestrated by the balance between enzymes responsible for active transport of PS from the outer to the inner leaflet (ATP11C) and those whose counteracts these activities (PLSCR1). Using quantitative real-time polymerase chain reaction and standard flow cytometry procedures, we hypothesized that the aberrant expression of either or both ATP11C and PLSCR1 transcripts may disrupt the PS internalization/externalization process and become clinically relevant for patients with sickle cell anemia (SCA). Overall, neither ATP11C/PLSCR1 ratio or ATP11C and PLSCR1 (if analyzed separately) had impact on risk to present acute or chronic organ damage in 178 patients with SCA. By collecting a new set of samples from SCA patients during a vaso-occlusive crisis (VOC, crisis state, 13 patients) and comparing with new samples of patients in steady state (15 patients), we noticed that patients in steady state exhibited mean values of ATP11C/PLSCR1 ratio significantly higher (mean value: 18.2, range, 0.3-53) than those who were in crisis (mean value: 3.7, range, 0.5-9) (P = 0.013). Most importantly, there was a strong inverse correlation between PS exposure and ATP11C/PLSCR1 ratio in sickle erythrocytes (Pearson correlation coefficient, r: - 0.78). Based on these findings, it is conceivable that the ATP11C/PLSCR1 ratio may switch from high to low during a VOC, although the underlying reasons require further investigations.

Made available in DSpace on 2022-04-28T17:22:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-09 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Seminal plasma has several components that protect the sperm cells and assist in the fertilization process. In contrast, the exact role carried out by seminal plasma during the cooling of canine semen remains controversial. Moreover, concerning the long estrus period, the possibility to store chilled semen at 5 degrees C for more than 72 hours and maintain good sperm quality for additional inseminations could increase fertilization rates. Thus, this study aimed to evaluate the seminal plasma influence on quality and oxidative stress of the extended canine semen stored at 5 degrees C for 7 days. Three ejaculate pools from eight healthy dogs were collected by digital manipulation of the penis. The sperm kinetics, sperm vitality (eosin/nigrosin stain), integrity of plasma and acrosomal membranes, morphology, superoxide and hydrogen peroxide production, mitochondrial potential, lipid peroxidation, and oxygen reactive species production (induced and spontaneous thiobarbituric acid [thiobarbituric acid reactive substances, TBARS] assay) were evaluated every 48 hours (M0, M48, M96, and M168) until 7 days (168 hours) in cooled extended (TRIS egg yolk) semen of dogs at 5 degrees C with (+SP) or without (-SP) autologous seminal plasma. No statistical difference was found for sperm kinetics in cooled samples with +SP and -SP during the experimental time period, except for the progressive motility of +SP samples that was higher at M48 than M96 (p = 0.023). The seminal plasma did not influence any other evaluated sperm characteristics. Finally, our results demonstrated that the presence or lack of seminal plasma during cooling the semen of dogs does not influence sperm quality at 5 degrees C. Moreover, the components of the semen extender may contribute to maintaining good sperm quality and low reactive oxygen species production during the long period of the dog's semen cooling, even after semen centrifugation. Sao Paulo State Univ UNESP, Fac Vet Med & Anim Sci, Dept Vet Surg & Anim Reprod, Rua Prof Dr Walter Mauricio Correa S-N, BR-18681681 Botucatu, SP, Brazil Univ Brasilia, Inst Biol Sci, Dept Physiol Sci, Brasilia, DF, Brazil Univ Sao Paulo, Fac Vet Med & Anim Sci, Dept Anim Reprod, Sao Paulo, Brazil Sao Paulo State Univ UNESP, Biosci Inst, Dept Biostat, Botucatu, SP, Brazil Sao Paulo State Univ UNESP, Fac Vet Med & Anim Sci, Dept Vet Surg & Anim Reprod, Rua Prof Dr Walter Mauricio Correa S-N, BR-18681681 Botucatu, SP, Brazil Sao Paulo State Univ UNESP, Biosci Inst, Dept Biostat, Botucatu, SP, Brazil FAPESP: 2017/02530-8 CAPES: 33004064086P1

Made available in DSpace on 2022-04-29T08:40:31Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-01-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) The apparent total tract digestibility (ATTD; trial 1) and the apparent (AID) and standardized (SID) ileal digestibility of the amino acids (AA) (trial 2) in flaxseed meal (FM) were evaluated with the addition of exogenous multi-carbohydrase (MC) and phytase (Phy). A total of 80 28-d-old broilers were allotted in a completely randomized design to receive treatments up to 35 d of age. A 2 × 2 factorial design is used to determine the enzyme effects, on the ATTD of dry matter, nitrogen, calcium, phosphorus and fiber, energy use, and the AID and SID of AA, in five replicate cages. There was synergism between MC and Phy on the ATTD of nitrogen and energy. The isolated inclusion of MC or Phy increased the ATTD of dry matter, calcium, phosphorus and fiber of FM. The enzyme inclusion on the AID and SID of AA in FM, established by comparing the means, suggested a better response to the addition of MC + Phy. Supplementation with Phy or combination of MC and Phy was a viable alternative to increase the ATTD of nutrients and energy. The combination of MC + Phy resulted in higher apparent and standardized digestibility of AA from FM. Department of Breeding and Animal Nutrition School of Veterinary Medicine and Animal Science São Paulo State University (UNESP), São Paulo Universidad Cientifica del Sur, Panamericana Sur, km 19, Lima 42 Department of Animal Science University of Sao Paulo, Av. Duque de Caxias Norte, 225, São Paulo Department of Breeding and Animal Nutrition School of Veterinary Medicine and Animal Science São Paulo State University (UNESP), São Paulo CAPES: 001 FAPESP: 2016/07352-8

The preparation, characterization and application of materials based on montmorillonite natural clay containing aluminum polyhydroxocomplexes of Keggin type ions (Al13) as intercalating agent and h...

Essential oils from the leaves and stems of Croton adenocalyx, C. grewioides, C. heliotropiifoliusand C. blanchetianusobtained through hydrodistillation were analyzed by GC-MS. We then investigated the lethal and sublethal effects of the Croton oils and 15 major constituents against Tetranychus urticae. β-Caryophyllene was the major component in the leaf and stem oils from C. heliotropiifoliusand C. adenocalyx. Spathulenol and (E)-anethole were the major constituents identified in the leaf and stem oils of C. blanchetianusand C. grewioides, respectively. The oil with the greatest lethal and sublethal effects was those from C. adenocalyx. Among the constituents β-caryophyllene and spatulenol were the most toxic to the mite, whereas eugenol and methyl eugenol were the most repellent. The toxicity and repellency of the Croton oils, particularly the oils from C. adenocalyx, demonstrate that these oils constitute a promising alternative to synthetic acaricides for use in the control of T. urticae.

Bimodal silica and aluminosilicate materials containing mesopores and macropores were synthesized by hydrothermal method using sodium silicate, aluminum nitrate, P123 triblock copolymer, n-decane, hydrochloric acid and water. The uncalcined silica compound was previously characterized by thermogravimetry, and the calcined materials were characterized by X-ray diffraction, infrared absorption spectroscopy, and scanning electron microscopy. The obtained materials have bimodal characteristics with mesopores and macropores in their structures, which pores are ideal for processing bulky molecules, such as hydrocarbons present in heavy oil. In this work, the synthesized silica and aluminosilicate were used as materials for distillation and cracking of a petroleum sample with oAPI = 17.4. The process was evaluated by thermogravimetry, in the temperature range from 25 to 900 °C, in a nitrogen atmosphere. The determination of activation energies (Ea) as a function of the degree of conversion was obtained by using the Ozawa–Flynn–Wall kinetic model and at heating rates of 5, 10 and 20 °C min−1. It was observed that the catalytic cracking of the oil presented Ea of 196 kJ mol−1 for 90% conversion. At the same conversion, for the oil containing 10% of Si-MBB catalyst, the Ea decreased to 170 kJ mol−1 and for AlSi-BMM, the Ea was 155 kJ mol−1, showing the efficiency of bimodal materials containing mesopores and macropores in its structure for processing of heavy oil.

Interleukin-2 (IL-2) is a classical pro-inflammatory cytokine known to display neuroprotective roles in the central nervous system including the retina. In the present study, we investigate the molecular targets involved in the neurotrophic effect of IL-2 on retinal ganglion cells (RGC) after optic nerve axotomy. Analysis of retrograde labeling of RGC showed that common cell survival mediators, as Trk receptors, Src, PI3K, PKC, and intracellular calcium do not mediate the neurotrophic effect of IL-2 on RGC. No involvement of MAPK p38 was also observed. However, other MAPKs as MEK and JNK appear to be mediating this IL-2 effect. Our data also indicate that JAK2/3 are important intracellular proteins for the IL-2 effect. Interestingly, we demonstrate that the IL-2 effect depends on dopamine D1 receptors (D1R), the cAMP/PKA pathway, interleukin-10 (IL-10), and NF-κB, suggesting that RGC survival induced by IL-2 encompasses a molecular network of major complexity. In addition, treatment of retinal cells with recombinant IL-10 or 6-Cl-pb (D1R full agonist) was able to increase RGC survival similar to IL-2. Taken together, our results suggest that after optic nerve axotomy, the increase in RGC survival triggered by IL-2 is mediated by IL-10 and D1R along with the intracellular pathways of MAPKs, JAK/STAT, and cAMP/PKA.

To evaluate in vitro transenamel/transdentinal of penetration of H2O2 after microabrasive. Computational models were performed to verify peroxide penetration and evaluate if geometric modifications could affect in vitro results. Enamel/dentin blocks from bovine incisors were prepared and randomly divided into groups (n = 15) according with abrasive (35% phosphoric acid and pumice or 6.6% hydrochloric acid and silica) and bleaching agents (16% carbamide peroxide and 35% H2O2). From artificial pulp chambers, the H2O2 concentration was measured and SEM was used for surface morphology. Numerical models were performed (Abaqus® v6.12) modifying slightly enamel/dentin thickness based on experimental data. All groups presented H2O2 penetration, although no significant difference was noted between the control and experimental groups (p > 0.05). The numerical analysis demonstrated the role of dental tissue thickness in the H2O2 penetration. Microabrasion is recommended as its association with bleaching procedures and small modifications in thicknesses of enamel/dentin can cause substantial changes in HP penetration. Such diffusion aspect is clinically relevant for the bleaching procedures since very thin enamel could present more peroxide propagation through dental tissues.

This study was conducted to evaluate the phenolic composition, toxicity, and antimicrobial activity of Licania rigida Benth, an underexploited wild Licania species. L. rigida leaf fractions (ethyl ...

NAD is a ubiquitous metabolic coenzyme. Although the role of NAD as a central redox shuttle remains of critical interest in plant metabolism, recent evidence indicates that NAD serves additional functions in signaling and regulation. A link with the plant stress hormone abscisic acid (ABA) has emerged on the basis of similar plant phenotypes following interference with NAD or ABA, especially in stomatal development, stomatal movements, responses to pathogens and abiotic stress insults, and seed germination. The association between NAD and ABA regulation appears specific and cannot be accounted for by pleiotropic interference. Here, we review the current picture of the NAD - ABA relationship, discuss emerging candidate mechanisms, and assess avenues to dissect interaction mechanisms.

‘Candidatus Liberibacter asiaticus’ is associated with the devastating citrus disease Huanglongbing (HLB). It is transmitted by grafting infected material to healthy plants and by the feeding of the Asian citrus psyllid (Diaphorina citri). Previously, we demonstrated that a metabolomics approach using proton-nuclear magnetic resonance spectroscopy discriminates healthy from diseased plants via grafting. This work assessed the capability of this technology in discriminating healthy and diseased plants when the bacterium is vectored by psyllids. One-year-old greenhouse-grown ‘Lisbon’ lemon trees were exposed to either carrier psyllids (exposed, n = 10), or psyllids that were free of ‘Candidatus Liberibacter asiaticus’ (control, n = 6). Leaf metabolites were tracked for 1 year and disease diagnosis was made using quantitative PCR. Overall, 31 water-soluble metabolites were quantified in leaves, including four sugars and 12 amino acids. Analysis via nonmetric multidimensional scaling and principal component analysis revealed significant differences between the leaf metabolome of control versus infected trees beginning at 8 weeks postexposure, including alterations in glucose and quinic acid concentrations. These findings provide a longitudinal overview of the metabolic effects of HLB during the early phases of disease, and confirm previous experimental work demonstrating that infection elicits changes in the leaf metabolome that enables discrimination between healthy and infected plants. Here we demonstrate that the mode of inoculation (i.e., graft versus psyllid) results in a similar pathology.

Human malaria continues to be a public health problem and an important cause of morbidity and mortality in the world. Malaria control is achieved through both individual protection against mosquito bites and drug treatment, which is hampered by the spread of Plasmodium falciparum resistance to most antimalarials, including artemisinin derivatives. One of the key pharmacological strategies for controlling malaria is to block transmission of the parasites to their mosquito vectors. Following this rational, MEFAS, a synthetic hybrid salt derived from artesunate (AS) and mefloquine has been previously reported for its activity against asexual P. falciparum parasites in vitro, in addition to a pronounced reduction in the viability of mature gametocytes. Herein, MEFAS was tested against asexual forms of Plasmodium vivax and for its ability to block malaria transmission in Anopheles darlingi mosquitoes in a membrane feeding assay using P. vivax field isolates. MEFAS demonstrated high potency, with a IC50 of 6.5 nM against asexual forms of P. vivax. At 50 μM, MEFAS completely blocked oocyst formation in mosquitoes, regardless of the oocyst number in the control group. At lower doses, MEFAS reduced oocyst prevalence by greater than 20%. At equivalent doses, AS irregularly reduced oocyst formation and caused only slight inhibition of mosquito infections. These results highlight the potential of MEFAS as a novel transmission-blocking molecule, as well as its high blood schizonticidal activity against P. vivax and P. falciparum field isolates, representing a starting point for further development of a new drug with dual antimalarial activity., Graphical abstract Image 1

One-step oxidative cleavage of cyclohexene to adipic acid using H2O2 as oxidizing agent and heteropolysalts as heterogeneous catalysts was successfully performed, without the use of additives, such as organic or inorganic acids. The K3PW12O40, K3PMo12O40, Cs3PW12O40 and Cs3PMo12O40 heteropolysalts were synthesized by ion exchange of the respective heteropolyacids using cesium and potassium carbonates. The catalysts were thermally treated at 200 or 600 °C and characterized by Raman spectroscopy, thermogravimetric analysis, X-ray fluorescence (XRF) and photoelectronic X-ray spectroscopy (XPS). Raman results showed that the Keggin structure of the polyoxometalates was successfully obtained for both heteropolyacids and heteropolysalts and remained stable even after thermal treatment at 600 °C. XRF analysis confirmed the insertion of the cations (Cs+ and K+) into the heteropolysalt structures. All catalysts completely converted cyclohexene within 24 h and they were selective to adipic acid. The best catalyst, K3PW12O40 calcined at 600 °C (KPW-600), achieved the highest adipic acid yield (83 %). In this work, we associate the best activity of the KPW-600 heteropolysalt not only to its greater acidity, but also to the higher concentration of (W-O-W)/W species (identified by XPS). Both properties are fundamental for the oxidation reaction of cyclohexene to adipic acid under the experimental conditions used. The results showed that the presence of peroxide species is essential, mainly to favor oxidation reactions, such as the Baeyer-Villiger rearrangement reaction. A reaction scheme for the oxidation of cyclohexene to adipic acid with the best catalyst (KPW-600), was proposed based on our kinetic studies and literature results. In addition to the main route of adipic acid formation from the direct oxidation of cyclohexene, undesirable parallel reactions of the rearrangement of 1,2 - cyclohexanediol and allyl oxidation were also observed. The influence of reaction conditions was also investigated, as well as the reuse of the most promising catalyst.

Hypothyroidism is a condition that affects multiple systems, including the central nervous system, causing, for example, cognitive deficits closely related to Alzheimer's disease. The flavonoid chrysin is a natural compound associated with neuronal improvement in several experimental models. Here, we evaluated the effect of chrysin on cognitive impairment in hypothyroid female mice by exploring neuroplasticity. Hypothyroidism was induced by continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. On the 32nd day, the animals showed low plasma levels of thyroid hormones (hypothyroid mice) than the control group (euthyroid mice). Subsequently, mice were intragastrically administered with vehicle or chrysin (20 mg/kg) once a day for 28 consecutive days. At the end of the treatments, behavioral tests were performed: open-field test (OFT) and morris water maze (MWM). Then, the levels of neurotrophins (BDNF and NGF) in the hippocampus and prefrontal cortex were measured and tested the affinity of chrysin with neurotrophinergic receptors through molecular docking. Hypothyroid mice showed memory deficit in the MWM and reduced neurotrophins levels in the hippocampus and prefrontal cortex, meanwhile, the chrysin treatment was able to reversed the deficit of spatial memory function and increased the levels of BDNF in hipocamppus and NGF in both structures. Additionally, molecular docking analysis showed that chrysin potentially binds to the active site of the TrkA, TrkB, and p75NTR receptors. Together, these findings suggest that chrysin reversed behavioral and neurochemical alterations associated with memory deficit induced by hypothyroidism, possibly by modulating synaptic plasticity in the neurotrophinergic system.

The bioalcohol production (ethanol and butanol) from lignocellulosic biomass has some techno-economic limitations nowadays. Detoxification technologies can efficiently remove fermentation inhibitors (such as furan aldehydes, aliphatic acids, and phenolic compounds) to increase the bioalcohol titers. However, the addition of more steps before fermentation increases the complexity of the production scheme and reduces the profit margin. Process intensification concepts have been disseminated as a critical factor for the success of biotechnological processes, including bioalcohol production. Thus, this review discusses the main inhibitors from lignocellulosic biomass and the in-situ technologies used to minimize the yeast inhibition in hydrolysates and slurries. In-situ detoxification strategies involve different fundamentals, but they have the unanimity of allowing fermentation to be carried out concurrently. They are usually based on the establishment of a microbial consortium as well as the addition of reducing agents, polymers, solvents and adsorbents. Also, in-situ product recovery methods have been developed to minimize energy consumption in downstream processing.

Atmospheric mercury (Hg) observations in the lower free troposphere (LFT) can give important insights into Hg redox chemistry and can help constrain Hg background concentrations on a regional level. Relatively continuous sampling of LFT air, inaccessible to most ground-based stations, can be achieved at high-altitude observatories. However, such high-altitude observatories are rare, especially in the Southern Hemisphere (SH), and atmospheric Hg in the SH LFT is unconstrained. To fill this gap, we continuously measured gaseous elemental mercury (GEM; hourly) and reactive mercury (RM; integrated over ∼ 6–14 d) for 9 months at Maïdo mountain observatory (2160 m a.s.l.) on remote Réunion Island (21.1∘ S, 55.5∘ E) in the tropical Indian Ocean. GEM exhibits a marked diurnal variation characterized by a midday peak (mean: 0.95 ng m−3; SD: 0.08 ng m−3) and a nighttime low (mean: 0.78 ng m−3; SD: 0.11 ng m−3). We find that this diurnal variation is likely driven by the interplay of important GEM photo-reemission from the islands' vegetated surfaces (i.e. vegetation + soil) during daylight hours (8–22 ng m−2 h−1), boundary layer influences during the day, and predominant LFT influences at night. We estimate GEM in the LFT based on nighttime observations in particularly dry air masses and find a notable seasonal variation, with LFT GEM being lowest from December to March (mean 0.66 ng m−3; SD: 0.07 ng m−3) and highest from September to November (mean: 0.79 ng m−3; SD: 0.09 ng m−3). Such a clear GEM seasonality contrasts with the weak seasonal variation reported for the SH marine boundary layer but is in line with modeling results, highlighting the added value of continuous Hg observations in the LFT. Maïdo RM is 10.6 pg m−3 (SD: 5.9 pg m−3) on average, but RM in the cloud-free LFT might be about twice as high, as weekly–biweekly sampled RM observations are likely diluted by low-RM contributions from the boundary layer and clouds.

The study aimed to investigate the chemical composition and the anti-inflammatory activity of the hydroethanolic rhizomes, stems, and leaf extracts of Renealmia petasites using in vitro and in vivo assays. The chemical composition of the extracts was characterized in a linear iron trap mass spectrometer. Total phenolic, flavonoid, and tannin content were determined by spectrophotometry analyses. In vitro anti-inflammatory activity was investigated in lipopolysaccharide-stimulated macrophages evaluating the influence on the production of superoxide anion (O2−), nitric oxide (NO), and the pro-inflammatory cytokines tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). In vivo effects were determined using the air pouch model in which were inoculated carrageenan and thereafter treated with 50 mg/kg of the hydroethanolic extracts of R. petasites. After 4 and 24 h, the cellular influx, protein exudation, cytokines, and nitric oxide were evaluated. Eight compounds were tentatively identified in the R. petasites extracts, suggesting five diarylheptanoids, one flavonoid, and two fatty alcohols. The in vitro results showed that the extracts were capable of blocking free radicals and/or inhibiting their intracellular actions by inhibiting the production of important mediators of the inflammatory process, such as NO, O2−, TNF-α, and IL-6. In vivo, R. petasites significantly decrease the influx of leukocytes, mainly neutrophils, protein exudation, NO, TNF-α, and IL-6 concentration in the air pouch model. The results evidenced that R. petasites can be considered a promising alternative therapy for the treatment and management of osteoarthritis and other inflammatory diseases.

Solar fuel production through the so-called artificial photosynthesis has attracted a great deal of attention to the development of a new world energy matrix that is renewable and environmentally friendly. This process is characterized by light absorption with enough photon energy to generate conduction electrons, which drive the carbon dioxide reduction to produce organic fuels. It is also common to couple Ru-complex electrocatalysts to form a more efficient and selective hybrid system for this application. In this work, we have undertaken a thorough investigation of the redox reaction mechanism of Ru-based electrocatalysts by means of density functional theory (DFT) methods under the experimental conditions that have been previously reported. More specifically, we have studied the electrochemistry and catalytic activity of the [Ru(bpy)(2)(CO)(2)](2+) coordination complex. Our theoretical assessment supports the following catalytic cycle: (i) [Ru(bpy)(2)(CO)(2)](2+) is transformed into [Ru(bpy)(2)(CO)](0) upon two-electron reduction and CO release; (ii) [Ru(bpy)(2)(CO)](0) is protonated to form the [Ru(bpy)(2)(CO)H](+) hydride complex; (iii) CO2 is activated by the hydride complex through an electrophilic addition to form the [Ru(bpy)(2)(CO)(OCHO)](+) intermediate; (iv) the resulting formic acid ligand is released in solution; and, finally, (v) the CO ligand is reattached to the complex to recover the initial [Ru(bpy)(2)(CO)(2)](2+) catalyst. Funding Agencies|Swedish Research Council (VR)Swedish Research Council; STandUP; CAPES (Coordenacao de Aperfeicoamento de Pessoal de Ensino Superior)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)

We investigated the effect of Alpinia zerumbet essential oil on the quality and shelf life of tambaqui (Colossoma macropomum) fillets stored under refrigeration (10.0 ± 0.5 °C) for 14 days. The treatments were A. zerumbet essential oil at 0.75% v v-1 (AEO 0.75%), A. zerumbet essential oil at 1.5% v v-1 (AEO 1.5%) and a control (no essential oil). The sample quality and shelf life were determined by the total psychrotrophic count (TPC) and chemical parameters (pH, total volatile basic nitrogen, centesimal composition and thiobarbituric acid reactive substances - TBARS) at zero, seven and 14 days of storage time. The TPC decreased significantly (p < 0.05) with an A. zerumbetessential oil level of 1.5% until seven days of storage. The concentration of A. zerumbet essential oil at 0.75% resulted in lower pH, TBARS, and TVBN values in comparison with the other treatment and the control. Thus, A. zerumbet essential oil was efficient in extending the shelf life of refrigerated tambaqui fillets up to approximately seven days. RESUMO Investigamos o efeito do óleo essencial de Alpinia zerumbet sobre a qualidade e vida útil de filés de tambaqui (Colossoma macropomum) armazenados sob refrigeração (10,0 ± 0,5 °C) durante 14 dias. Os tratamentos foram óleo essencial de A. zerumbet (OEA) a 0,75% v v-1 (OEA 0,75%) e 1,5% v v 1 (OEA 1,5%), além de um controle (sem OEA). A qualidade e vida útil das amostras foram determinadas por contagem psicrotrófica total (CPT) e parâmetros químicos (pH, bases nitrogenadas voláteis totais, composição centesimal e substâncias reativas ao ácido tiobarbitúrico - SRATB), nos dias zero, sete e 14 de armazenamento. O TPC diminuiu significativamente (p < 0,05) com óleo essencial de A. zerumbet a 1,5% por até sete dias de armazenamento. O tratamento contendo OEA a 0,75% resultou em menores valores de pH, SRTAB e BNV-T em comparação ao outro tratamento e ao controle. Portanto, o óleo essencial de A. zerumbet foi eficiente para prolongar a vida útil do filé de tambaqui por aproximadamente sete dias.

The present study investigated the possible influence of enzymatic browning of banana peel over the production of silver nanoparticles (AgNPs). Firstly, aqueous extracts of banana peel were prepared at different times after peeling and they were used as reducing and stabilizing agents for the production of AgNPs as monitored by visual inspection and spectrophotometry. Hydrodynamic diameters, polydispersity indexes, and Zeta potentials of the produced AgNPs were evaluated. Besides, antimicrobial activities of the AgNPs produced in the moment of peeling and after up to 2 h were assessed. As longer the period of time passed after peeling, AgNPs produced showed a tendency to decrease the size, to become with Zeta potential more negative, and to stabilize their polydispersity indexes. Antimicrobial assays showed that the two tested AgNPs were similarly effective against Escherichia coli and Staphylococcus aureus at 128 and 256 μM, respectively. This study demonstrated that banana peels extracts obtained after different times affected the production of AgNPs in different manners, producing AgNPs with distinct characteristics, such as hydrodynamic diameter, Zeta potential, and polydispersity index. Moreover, all tested AgNPs showed antimicrobial activity.

Biosorption has been examined for the treatment of aqueous solutions containing uranium, a radiotoxic pollutant. Nevertheless, the evaluation of the role of process variables by experimental design on the use of hydroxyapatite and bone meal as biosorbents for uranium has not yet been previously addressed. In this study, the effects of adsorbent dosage (M), initial uranium concentrations ([U]0), and solution pH were investigated, using a two-level factorial design and response surface analysis. The experiments were performed in batch, with [U]0 of 100 and 500 mg L−1, pH 3 and 5, and adsorbent/uranium solution ratios of 5 and 15 g L−1. Contact time was fixed at 24 h. Removal rates were higher than 88%, with a maximum of 99% in optimized conditions. [U]0 and M were found to be the most influential variables in U removal in terms of adsorption capacity (q). The experiments revealed that bone meal holds higher adsorption capacity (49.87 mg g−1) and achieved the highest uranium removal (~ 100%) when compared to hydroxyapatite (q = 49.20 mg g−1, removal = 98.5%). The highest value of q for both biomaterials was obtained for [U]0 = 500 mg L−1, pH 3, and M = 5 g L−1. Concerning the removal percentage, bone meal achieved the best performance for [U]0 = 500 mg L−1, pH 3, and M = 15 g L−1. Further experiments were made with real radioactive waste, resulting in a high uranium adsorption capacity for both materials, with 22.11 mg g−1 for hydroxyapatite and 22.08 mg g−1 for bone meal, achieving uranium removal efficiencies higher than 99%.

Poultry litter is widely applied as a fertilizer even though it is one of the main antibiotic sources to agricultural soils. Long-term sublethal effects (56 days) on the antioxidant system of Eisenia andrei earthworms following exposure to fluoroquinolone-contaminated poultry litter (enrofloxacin + ciprofloxacin) at 5.0, 10, and 20 g kg-1 were evaluated. The following biomarkers were assessed: superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), reduced glutathione (GSH), and a lipid peroxidation (LPO) proxy. Significant CAT and SOD increases, and a moderate positive correlation (ρ = 0.67, p < 0.05) between these enzymes was observed. Glutathione-S-transferase levels increased significantly at 10 g kg-1, while GSH exhibited a dose-dependent response at 5.0 mg kg-1 (4-106%), 10 mg kg-1 (28-330 %), and 20 mg kg-1 (45-472%). LPO levels exhibited a decreasing trend with increasing poultry litter concentrations of 8-170% (5.0 g kg-1), 7-104% (10 mg kg-1), and 3-6% (20 mg kg-1). A principal component analysis (PCA) highlighted increased SOD and CAT activities, possibly due to increased reactive oxygen species (ROS) concentrations. Biological health status assessments based on the biomarker response index indicate major alterations in the first month of exposure and becoming moderate in the second month. These findings indicate an antioxidant system attenuation trend. It is possible, however, that successive poultry litter applications may reduce the long-term recovery capacity of the evaluated biomarkers.

Made available in DSpace on 2022-04-28T19:46:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-02-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) The study aimed to identify and quantify the metabolites profile and metabolic pathways in human muscle tissue engaged during exhaustive high-intensity cycling exercise. Seven healthy physically active men performed a graded exercise test and an exhaustive supramaximal effort at 115% of maximal aerobic power with muscles biopsies performed in rest and immediately after exhaustion for quantifying of muscle metabolites changes by 1H-NMR spectroscopy. The time until exhaustion (tlim) recorded was 224.7 ± 35.5 s whereas the muscle pH at exhaustion was 6.48 ± 0.05. A total of 54 metabolites were identified and quantified. The most enriched and impacted pathways included: beta oxidation of very long chain fatty acids, mitochondrial electron transport chain, alanine aspartate, and glutamate metabolism, citric acid cycle, arginine biosynthesis, propanoate metabolism, threonine and 2-oxobutanoate degradation and pyruvate metabolism. In addition, the muscle concentrations in Post exercise, compared to Pre increased significantly (p

Herbicide-resistant weed management is one of the greatest agricultural challenges in crop production. Thus, the quick identification of herbicide-resistant weeds is extremely important for management. This study aimed to evaluate resistance to PSI-inhibiting herbicides (diquat) and physiological response to paraquat application in Sumatran fleabane [Conyza sumatrensis (Retz.) E. Walker; syn.: Erigeron sumatrensis Retz.]. The research was conducted with two C. sumatrensis biotypes, one susceptible and the other with multiple resistance to herbicides from five different modes of action (glyphosate, paraquat, diuron, saflufenacil, and 2,4-D). A dose–response assay was carried out to evaluate herbicide resistance to diquat in the paraquat-resistant C. sumatrensis biotype. The enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and ascorbate peroxidase (APX), hydrogen peroxide (H2O2) content, and chlorophyll a (Chl a) fluorescence were measured in both biotypes after paraquat (400 g ai ha−1) application. The dose–response assay confirmed resistance of C. sumatrensis to diquat with resistance factor levels of 26-fold and 6-fold for LD50 and GR50 values, respectively, compared with the susceptible biotype. Accumulation of H2O2 occurred more rapidly in the paraquat-susceptible biotype than in the resistant one. Paraquat treatment caused an increase in SOD and APX activity in the susceptible biotype, but antioxidant enzyme activities were unaffected by paraquat in the resistant one at 5 h after application (HAA). Chl a fluorescence increased across the first 4 HAA in both resistant and susceptible biotypes. However, at 24 HAA, the resistant biotype showed a decline in fluorescence close to untreated plants, while the susceptible biotype died, confirming resistance to diquat in the paraquat-resistant C. sumatrensis biotype. The paraquat-resistant biotype does not induce antioxidative enzymes, as a possible mechanism of resistance to paraquat, but shows rapid recovery of photosynthesis and continuous growth when subjected to paraquat, while the paraquat-susceptible biotype does not survive.

Background Self-emulsifying drug delivery systems (SEDDSs) have attracted attention because of their effects on solubility and bioavailability of lipophilic compounds. Herein, a SEDDS loaded with lycopene purified from red guava (nanoLPG) was produced. The nanoemulsion was characterized using dynamic light scattering (DLS), zeta potential measurement, nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), lycopene content quantification, radical scavenging activity and colloidal stability in cell culture medium. Then, in vivo toxicity and tissue distribution in orally treated mice and cytotoxicity on human prostate carcinoma cells (DU-145) and human peripheral blood mononuclear cells (PBMC) were evaluated. Results NanoLPG exhibited physicochemical properties with a size around 200 nm, negative zeta-potential, and spherical morphology. The size, polydispersity index, and zeta potential parameters suffered insignificant alterations during the 12 month storage at 5 °C, which were associated with lycopene stability at 5 °C for 10 months. The nanoemulsion showed partial aggregation in cell culture medium at 37 °C after 24 h. NanoLPG at 0.10 mg/mL exhibited radical scavenging activity equivalent to 0.043 ± 0.002 mg Trolox/mL. The in vivo studies did not reveal any significant changes in clinical, behavioral, hematological, biochemical, and histopathological parameters in mice orally treated with nanoLPG at 10 mg/kg for 28 days. In addition, nanoLPG successfully delivered lycopene to the liver, kidney and prostate in mice, improved its cytotoxicity against DU-145 prostate cancer cells—probably by pathway independent on classical necrosis and apoptosis—and did not affect PBMC viability. Conclusions Thus, nanoLPG stands as a promising and biosafe lycopene delivery system for further development of nanotechnology-based health products. Graphical Abstract

Background Intermittent androgen deprivation therapy (ADT) in biochemically recurrent castration-naive prostate cancer is non-inferior to continuous therapy. We hypothesised that finite-duration abiraterone acetate plus prednisone (Abi +P) added to ADT will further reduce the duration of treatment exposure by prolonging time to prostate-specific antigen (PSA) recurrence without impacting eugonad state recovery. Methods This phase II, randomised, open-label trial enrolled patients with rising PSA ≥ 0.2 ng/ml after radical prostatectomy and/or a PSA ≥ 1 following radiotherapy. Patients were randomised 1:1 to receive Abi (1 g PO daily) + P (5 mg PO daily) + ADT or ADT alone for 8 months. The primary end-point was PSA-free survival difference at 1 year following completion of therapy. Results Between February 2013 and July 2016, 200 patients were enrolled. Of 100 patients randomised to each arm, 99 in the Abi +P arm and 98 in the ADT arm were evaluable. Median follow-up was 64.4 months. Median PSA-free survival was 27.0 months for the Abi +P-treated group versus 19.9 months for the ADT-treated group (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.47–0.87). The PSA-free survival at 1 year post-treatment completion was 98% for the Abi +P group and 88% for the ADT group. Median time to eugonad state was 13.1 months for the abiraterone-treated group and 12.8 months for the ADT-treated group. Median eugonad PSA-free survival was 12.5 months for the abiraterone-treated group versus 9.0 for the ADT-treated group (HR 0.72, 95% CI 0.53–0.98). There were no significant between-group differences in androgen deprivation-related adverse events. Conclusions In men with biochemically recurrent prostate cancer following definitive treatment of the primary, finite duration treatment with ADT and Abi +P results in a significantly longer PSA relapse-free interval than treatment with ADT alone.

We aimed to identify presurgical and surgical risk factors for intraoperative complications in patients with pheochromocytomas. A retrospective study of patients with pheochromocytomas who underwent surgery in ten Spanish hospitals between 2011 and 2021 was performed. One hundred and sixty-two surgeries performed in 159 patients were included. The mean age was 51.6 ± 16.4 years old and 52.8% were women. Median tumour size was 40 mm (range 10–110). Laparoscopic adrenalectomy was performed in 148 patients and open adrenalectomy in 14 patients. Presurgical alpha- and beta-blockade was performed in 95.1% and 51.9% of the surgeries, respectively. 33.3% of the patients (n = 54) had one or more intraoperative complications. The most common complication was the hypertensive crisis in 21.0%, followed by prolonged hypotension in 20.0%, and hemodynamic instability in 10.5%. Patients pre-treated with doxazosin required intraoperative hypotensive treatment more commonly than patients pre-treated with other antihypertensive drugs (51.1% vs 26.5%, P = 0.002). Intraoperative complications were more common in patients with higher levels of urine metanephrine (OR = 1.01 for each 100 μg/24 h, P = 0.026) and normetanephrine (OR = 1.00 for each 100 μg/24 h, P = 0.025), larger tumours (OR = 1.4 for each 10 mm, P < 0.001), presurgical blood pressure > 130/80 mmHg (OR = 2.25, P = 0.027), pre-treated with doxazosin (OR = 2.20, P = 0.023) and who had not received perioperative hydrocortisone (OR = 3.95, P = 0.008). In conclusion, intraoperative complications in pheochromocytoma surgery are common and can be potentially life-threatening. Higher metanephrine and normetanephrine levels, larger tumour size, insufficient blood pressure control before surgery, pre-treatment with doxazosin, and the lack of treatment with perioperative hydrocortisone are associated with higher risk of intraoperative complications.

The antiproliferative activity of [Mn(CO)3(N^N)Br] (N^N = phendione 1, bipy 3) and of the two newly synthesized Mn complexes [Mn(CO)3(acridine)(phendione)]OTf (2) and [Mn(CO)3(di-triazole)Br] (4) has been evaluated by MTS against three tumor cell lines A2780 (ovarian carcinoma), HCT116 (colorectal carcinoma), HCT116doxR (colorectal carcinoma resistant to doxorubicin), and in human dermal fibroblasts. The antiproliferative assay showed a dose-dependent effect higher in complex 1 and 2 with a selectivity toward ovarian carcinoma cell line 21 times higher than in human fibroblasts. Exposure of A2780 cells to IC50 concentrations of complex 1 and 2 led to an increase of reactive oxygen species that led to the activation of cell death mechanisms, namely via intrinsic apoptosis for 2 and autophagy and extrinsic apoptosis for 1. Both complexes do not target DNA or interfere with cell cycle progression but are able to potentiate cell migration and neovascularization (for 2) an indicative that their application might be directed for initial tumor stages to avoid tumor invasion and metastization and opening a new avenue for complex 2 application in regenerative medicine. Interestingly, both complexes do not show toxicity in both in vivo models (CAM and zebrafish).

Erectile dysfunction (ED) is considered a public health problem with numerous risk factors, such as hypertension. Besides the existing oral treatment for ED, there are individuals that do not respond to or present numerous side effects to this therapy. Changes in the TRP channels can lead to several clinical complications, such as hypertension. More specifically, the cooling-sensing TRPM8 channel could be a novel target for the development of new drugs. In this line, menthol, a natural product TRPM8 channel agonist may be a molecule for use to treat erectile dysfunction. Then, we conducted a patent review to evaluate the application of menthol focusing on the treatment of erectile dysfunction. The search was conducted on Espacenet® associating A61K31/045 and A61K36/534 codes or using keywords, “erectile dysfunction AND menthol”. We analyzed 1,331 patents, which fourteen patents were found with the use of menthol in the genitourinary system. Although the patents had menthol in their formulations, none went directly to the development of pharmaceutical applications to treat erectile dysfunction. Taking these data into account, the use of menthol in the treatment of erectile dysfunction has been underexplored and is an opportunity for research and technological development based on a high innovation potential.

In this work, graphene oxide (GO) was synthesized by the modified Hummers method. The nanomaterial was characterized by FTIR and Raman spectroscopy, SEM, and pH at the point of zero charge. GO exhibited typical characteristics of graphene-based materials, indicating that graphite oxidation and exfoliation occurred successfully. Cd (II) and Pb (II) adsorption onto GO was carried out in batch systems, in which the effect of adsorbent dosage, contact time, and initial adsorbate concentration were evaluated. Langmuir, Freundlich, and Sips isotherm models, as well as pseudo order models and Elovich kinetic equation were applied to adsorption experimental data. Results indicated that increasing adsorbent mass, the removal efficiency of Cd (II) and Pb (II) increased. Freundlich isotherm better described Pb (II) adsorption (R2 = 0.96), while Cd (II) isotherm showed linear behavior. From the Akaike’s AIC parameter, kinetic data were satisfactorily described by pseudo-first order (Cd (II)) and pseudo-n order (Pb (II)) models. GO was successfully subjected to five regeneration cycles, maintaining high efficiency (> 90%) in all cycles. GO showed high potential for the adsorption of Cd (II) and Pb (II) from aqueous solution, due to its high adsorption capacity, rapid Cd (II) and Pb (II) intakes, and great regeneration performance.

As ureases são enzimas que catalisam a hidrólise da ureia, formando amônia, gás carbônico e água. A hidrólise da ureia desempenha um papel importante no ciclo do nitrogênio, pois fornece esse elemento para o crescimento de microrganismos e plantas. Entretanto, a ação excessiva da urease leva à vários problemas em organismos vivos e, também, pode causar danos ambientais e econômicos. Os inibidores de urease podem ser uma boa alternativa para o tratamento de doenças causadas por microrganismos patogênicos dependentes da enzima urease. A curcumina, um produto natural obtido da Curcuma longa, é conhecida no Brasil como açafrão, e possui uma estrutura com capacidade de complexar metais, tornando-a um potencial inibidor de metaloproteínas, como a urease. Por esse motivo, nesse trabalho foi avaliado o potencial de interação da curcumina e de onze análogos com o sítio ativo da enzima urease utilizando os programas Autodock e Mopac2016. Os resultados mostraram que nove compostos possuem maior interação com o sítio ativo da enzima urease quando comparados com o substrato ureia, apresentando energias de ligação entre -7,24 e -5,12 kcal/mol, enquanto a ureia apresentou energia de ligação igual a -4,10 kcal/mol. O produto natural curcumina ficou na quinta posição, apresentando energia de ligação de -6,21 kcal/mol, demonstrando grande potencial para o uso como inibidor da enzima urease.

Synaptic inhibition is essential for shaping the dynamics of neuronal networks, and aberrant inhibition is linked to epilepsy. Gephyrin (Geph) is the principal scaffolding protein at inhibitory synapses and is essential for postsynaptic clustering of glycine (GlyRs) and GABA type A receptors. Consequently, gephyrin is crucial for maintaining the relationship between excitation and inhibition in normal brain function and mutations in the gephyrin gene (GPHN) are associated with neurodevelopmental disorders and epilepsy. We identified bi-allelic variants in the GPHN gene, namely the missense mutation c.1264G > A and splice acceptor variant c.1315-2A > G, in a patient with developmental and epileptic encephalopathy. We demonstrate that the splice acceptor variant leads to nonsense-mediated mRNA decay. Furthermore, the missense variant (D422N) alters gephyrin structure, as examined by analytical size exclusion chromatography and circular dichroism-spectroscopy, thus leading to reduced receptor clustering and sensitivity towards calpain-mediated cleavage. In addition, both alterations contribute to an observed reduction of inhibitory signal transmission in neurons, which likely contributes to the pathological encephalopathy.

Lippia sidoides is a typical shrub from Brazil that has been used in traditional medicine. This is a systematic review on the effect of L. sidoides for controlling dental plaque, gingivitis, and periodontitis. A database search through May 2021 in Medline/PubMed, SCOPUS, BVS, and Web of Science identified 711 reports of which 17 met our inclusion criteria. Five randomized controlled trials and three animal studies were included that compared L. sidoides-based products (toothpaste, mouthrinse, and gel) to cetylpyridinium chloride, chlorhexidine, and placebo products. Among the human studies, a significant antiplaque effect after treatment with L. sidoides-based products was observed in three studies and an antigingivitis effect in two studies, similar to chlorhexidine-based products. One study found superior dental plaque reduction compared to cetylpyridinium chloride mouthrinse. Only one study testing a L. sidoides gel found no antiplaque effect. Among the animal studies, an L. sidoides mouthrinse significantly reduced calculus in two studies, inflammatory infiltrate in one study, and plaque bacteria and gingivitis in one study. An L. sidoides gel significantly reduced alveolar bone loss and inflammatory response in one study in which mice were submitted to ligature-induced periodontal disease. In general, L. sidoides-based products were effective in reducing dental plaque and calculus formation, as well as clinical signs of gingivitis. As most studies present methodological limitations, these results should be interpreted carefully. Further clinical trials with greater methodological accuracy and control of biases are necessary for the use of L. sidoides-based products in humans to be viable in clinical practice.

We present a study on the structural and phonon properties of cobalt-doped orthorhombic molybdenum trioxide (α-MoO3:xCo) hierarchical microrods. The samples were synthesized by solid-state reaction with molar concentrations of 0%, 1%, 3%, and, 5% cobalt. X-ray diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM), and Fourier transformed infrared spectroscopy (FTIR) were used to confirm the orthorhombic phase and the structural properties of each sample. The infrared and Raman spectra of the samples show that doping alters the ratio of relative intensities, linewidth, and the shift of the wavenumber of the modes, and a correlation is established between the stretching force constant and wavenumber. Experimental temperature-dependent Raman scattering studies were performed on samples of α-MoO3:xCo over a temperature range of 298–813 K. The Raman spectra showed a phase transition at around 373 K to a self-similar structure, indicating a possible isostructural phase transition (IPT) for samples with 0% and 1% cobalt, a phenomenon rarely reported in the literature. Nevertheless, this phase transition was not observed for samples containing 3% and 5% cobalt, indicating an increase in material stability.

Piper multinodum C.DC. belongs to the Piperaceae family, and is known as “Jaborandi-manso”. This species has no reported botanical, chemical, pharmacological and/or toxicological scientific studies, and has restricted occurrence in degraded Brazilian biomes. The Piper genus is known to be aromatic, the essential oils (EO) obtained from different organs have demonstrated significant biological activities, and can be an important tool for chemophenetic and ecological definitions. The present study aimed to characterize the chemical profile of the EO from different parts of P. multinodum and their activity against Mycobacterium tuberculosis H37Rv (ATCC, 25618). The EO were obtained by hydrodistillation and characterized by GC-MS and GC-FID. Chemical composition of the volatile mixture showed a great diversity of compounds that diverged between the vegetative and reproductive parts. The α-pinene compound was identified as being the most predominant in the leaves, infructescences and inflorescences (32.49, 67.23 and 40.23%, respectively). The branches (secondary stem) showed to be rich in sesquiterpenes and monoterpenes: α-copaene (13.24%), E-caryophyllene (12.32%), α-pinene (20.34%), and myrcene (11.23%). The chemical profile of stems and roots showed a low percentage of monoterpenes and sesquiterpenes, but a high percentage of arylpropanoids, with E-methyl-isoeugenol (77.58%) registered in the stems and euasarone (81.34%) in the root. The antimycobacterial activity showed the highest activities recorded for the EO from roots (78.51 µg/mL) and infructescences (85.91 µg/mL). In addition to the findings related to biological activity, the determination of chemical diversification between the different parts of P. multinodum may help to understand the ecological issues of the Piperaceae family as well as to improve the chemotaxonomic knowledge of the genus Piper. Key words: Piper multinodum; essential oils; antimycobacterial activity; chemical composition.

The seed reserves with 148 days after anthesis are sufficient to form 100% normal seedlings in vitro, obtaining a production gain of 101 days. Euterpe edulis (Arecaceae) is a typical palm of the Atlantic Forest with great ecological and economic value. Its seeds are characterized by hard coats, as well as recalcitrant, slow, and uneven germination, which hinder efficient seedling production. Given its risk of extinction, the objective of this study was to investigate reserve mobilization and how this impacted on the quality of maturing E. edulis seeds. Seven maturation stages separated by 20-day intervals, were assessed from 108 to 228 days after anthesis. The morphological characteristics, germination, vigor, and biochemical properties of in vitro germinated seeds, as well as the quality of the seedlings from each maturation stage were assessed. Four replications with ten seeds were evaluated at each stage. Over the experimental period, total relative growth rate of the fruits was 0.0037 mm day− 1, while moisture content decreased from 79.49 to 46.59%. The concentrations of phenols, soluble sugar, proteins, and starch decrease significantly during maturation, while there is an increase in lipids and fibers. Most variables displayed a positive correlation, except moisture, phenols, soluble sugar, proteins, and starch. E. edulis seeds possessed sufficient reserves to allow for normally developed embryos 148 days after anthesis, their 100% germination, and formation of 100% normal seedlings.

Prostate cancer (PCa) that progresses after androgen deprivation therapy (ADT) remains incurable. The underlying mechanisms that account for the ultimate emergence of resistance to ADT, progressing to castrate-resistant prostate cancer (CRPC), include those that reactivate androgen receptor (AR), or those that are entirely independent or cooperate with androgen signaling to underlie PCa progression. The intricacy of metabolic pathways associated with PCa progression spurred us to develop a metabolism-centric analysis to assess the metabolic shift occurring in PCa that progresses with low AR expression. We used PCa patient-derived xenografts (PDXs) to assess the metabolic changes after castration of tumor-bearing mice and subsequently confirmed main findings in human donor tumor that progressed after ADT. We found that relapsed tumors had a significant increase in fatty acids and ketone body (KB) content compared with baseline. We confirmed that critical ketolytic enzymes (ACAT1, OXCT1, BDH1) were dysregulated after castrate-resistant progression. Further, these enzymes are increased in the human donor tissue after progressing to ADT. In an in silico approach, increased ACAT1, OXCT1, BDH1 expression was also observed for a subset of PCa patients that relapsed with low AR and ERG (ETS-related gene) expression. Further, expression of these factors was also associated with decreased time to biochemical relapse and decreased progression-free survival. Our studies reveal the key metabolites fueling castration resistant progression in the context of a partial or complete loss of AR dependence.