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Our knowledge of the bioactivity of silicon titanium oxide nanoparticles (TiSiO4 NPs) in crops is scarce, contrarily to TiO2NPs and SiO2NPs that are used in many industrial sectors, and have emerged in nanoagriculture (e.g., as pesticides or nanofertilisers). To evaluate the potential of using TiSiO4 NPs in nanoagriculture, it is necessary to characterize their potential benefits on crops and the safety doses. Here, we report for the first time the bioactivity of TiSiO4 NPs (up to 100 mg/L) in the model crop lettuce (Lactuca sativa L.) exposed for three weeks (from seeds/seedlings to pre-harvesting phase). The doses applied did not compromise the germination rate, and highly stimulated plant fresh matter. TiSiO4 NPs had beneficial effects on photochemical processes by increasing chlorophyll levels. Effects on photosynthesis are less evident but TiSiO4 NPs (100 mg/L) stimulated the photosynthetic potential, increasing Fv/Fm and ETR when compared to the 50 mg/L conditions. TiSiO4 NPs did not influence the net photosynthetic rate and other Calvin-cycle variables. Soluble sugars and starch levels were overall maintained. In general, this first report on TiSiO4 NPs bioactivity suggests that they did not have a toxic effect, and may be used to potentiate crops’ growth. Principal component analysis (PCA) also shows that despite effects on photosynthetic performance is minimal regarding the control, the 50 and 100 mg/L doses strongly differ, with the lower dose promoting mostly pigment accumulation, while the higher dose slightly stimulates Photosystem II efficiency including the electron transport rate and other gas exchange parameters.

C19H24N2O6, monoclinic, P21 (no. 4), a = 8.3611(7) Å, b = 9.0521(8) Å, c = 13.8988(8) Å, β = 106.710(5)°, V = 1007.52(14) Å3, Z = 2, Rgt(F) = 0.0428, wRref(F2) = 0.1174, T = 293(2) K.

C17H23NO5, monoclinic, P21 (no. 4), a = 6.0479(9) Å, b = 9.7032(10) Å, c = 14.711(2) Å, β = 94.174(9)°, V = 861.0(2) Å3, Z = 2, Rgt(F) = 0.0440, wRref(F2) = 0.1436, T = 293(2) K.

C18H24N2O5, monoclinic, P21/c (no. 14), a = 11.4784(7) Å, b = 9.0180(8) Å, c = 17.9483(17) Å, β = 92.823(7)°, V = 1855.6(3) Å3, Z = 4, Rgt(F) = 0.0505, wRref(F2) = 0.1611, T = 293 K.

Irrigation has been considered a controversial practice in European traditional viticulture due to potential alterations in the balance between vegetative growth and yield. In this regard, the influence of surface (DI) and subsurface (SDI) drip irrigation on physiological performance of the ‘Godello’ grapevine (Vitis vinifera L.) cultivar was compared with a non-irrigated control (R) over three consecutive growing seasons (2012- 2014) in NW Spain. Irrigation improved vine water status; R plants reached a minimum of midday leaf water potential of –1.5 MPa, whereas DI and SDI plants reached –1.3 MPa. Stomatal conductance was unaffected by irrigation as well as chlorophyll a fluorescence. However, photosynthetic pigments were present at higher concentrations in leaves from irrigated plants than in those from R plants in 2013. In addition, R plants showed higher values for the indicators of oxidative damage. No significant yield improvements were observed for irrigated plants, although the trend was to obtain slightly higher yields under irrigation in years with low rainfall amounts. This may not encourage growers to establish irrigation systems on their vineyards. However, these results may be important with the objectives of stabilizing yield from year to year.

This paper aims to show that the problem of personal identity is a fundamental question of the classical Indian thought. Usually we tend to think that personal identity is a Western philosophical subject, and so we tend to forget the significance of the Self (Atman) in Hinduism and even in Buddhism. The author shows how the Indian thought approached the question of personal identity and which was the singular solution outlined in the work consensually attributed to Gotama, the Buddha.

There is great interest nowadays in the use of preparative liquid chromatography as an effective tool for the production of enantiomerically pure, or enriched, compounds for the pharmaceutical industry. To make the chromatographic process economically attractive, attention is now focused on the choice of the chromatographic operating mode to minimize eluent consumption and to maximize productivity. Among the alternatives to the traditional batch chromatography, attention is now shifting towards simulated moving bed (SMB) technologies and a review covering the latest developments in this area seems timely. Several aspects of this important analytical technique are presented and details concerning the SMB technology for process optimization are outlined.

Two concise and enantioselective syntheses of the necine base precursors (1R,5R)-N-Cbz and N-Boc-2-oxa-6-azabicyclo[3.3.0]octan-3-ones (Geissman-Waiss lactones) were carried out from two enantiomerically pure endocyclic five-membered enecarbamates with overall yields of 23% and 26%, respectively. The synthetic strategy made use of a highly effective and stereoselective [2+2]cycloaddition of enantiomerically pure endocyclic enecarbamates with dichloroketene, as well as an efficient decarboxylation step of a bicyclic alpha-amino acid employing Boger's acyl selenide protocol employing tributyltin hydride. Interesting aspects concerning the regiochemical outcome of Baeyer-Villiger oxidations of bicyclic cyclobutanones are also reported, in which the usual stereoelectronic bias of Baeyer-Villiger oxidation seems to be counterbalanced by steric effects on the putative Criegee intermediate.

Controlled nuclear fusion aims to obtain energy by particles collision confined inside a nuclear reactor (Tokamak). These ionized particles, heavier isotopes of hydrogen, are the main elements inside of plasma that is kept at high temperatures (millions of Celsius degrees). Due to high temperatures and magnetic confinement, plasma is exposed to several sources of instabilities which require a set of procedures by the control and data acquisition systems throughout fusion experiments processes. Control and data acquisition systems often used in nuclear fusion experiments are based on the Advanced Telecommunication Computer Architecture (AdvancedTCA®) standard introduced by the Peripheral Component Interconnect Industrial Manufacturers Group (PICMG®), to meet the demands of telecommunications that require large amount of data (TB) transportation at high transfer rates (Gb/s), to ensure high availability including features such as reliability, serviceability and redundancy. For efficient plasma control, systems are required to collect large amounts of data, process it, store for later analysis, make critical decisions in real time and provide status reports either from the experience itself or the electronic instrumentation involved. Moreover, systems should also ensure the correct handling of detected anomalies and identified faults, notify the system operator of occurred events, decisions taken to acknowledge and implemented changes. Therefore, for everything to work in compliance with specifications it is required that the instrumentation includes hardware management and monitoring mechanisms for both hardware and software. These mechanisms should check the system status by reading sensors, manage events, update inventory databases with hardware system components in use and maintenance, store collected information, update firmware and installed software modules, configure and handle alarms to detect possible system failures and prevent emergency scenarios occurrences. The goal is to ensure high availability of the system and provide safety operation, experiment security and data validation for the fusion experiment. This work aims to contribute to the joint effort of the IPFN control and data acquisition group to develop a hardware management and monitoring application for control and data acquisition instrumentation especially designed for large scale tokamaks like ITER.

Diacetylenic phosphatidylcholines are synthetic compounds analogous to natural phospholipids. These molecules can be hydrated to form bilayered aggregates known as liposomes in a manner similar to natural phosphatidylcholines. A particular feature of these liposomes is their capability of undergoing polymerization when submitted to ultraviolet (UV) light irradiation. This process allows the construction of polymerized liposomes possessing interesting physical properties making these vesicles appropriate for slow-release drug delivering systems. In this article we describe the total syntheses of diacetylenic phosphatidylcholines 1,2-bis(10',12'-heptadecadiynoyl)-sn-glycero-3-phosphatidylcholine (1a), 1,2-bis(10',12'-tricosadiynoyl)-sn-glycero-3-phosphatidylcholine (1b) and 1,2-bis(4',6'-tricosadiynoyl)-sn-glycero-3-phosphatidylcholine (1c). Phospholipids 1a and 1c, displaying the butadiinyl chromophores closer to the chain terminus, or closer to the polar heads respectively, have not been reported before. Noteworthy was the observation that liofilization of the diacetylenic alcohols and acids intermediates significantly reduced undesired polymerization, allowing to stock these compounds for a short period of time (~24 h).

The first total synthesis of the antineoplastic marine natural product metachromin-A (1) was accomplished through a convergent synthetic approach amenable to the preparation of analogues for biological studies. The synthesis involved twelve steps in its longest sequence and sixteen steps overall. The total synthesis of the racemic metachromin-A features: (1) an efficient synthesis of the quinone intermediate 11; (2) efficient protocols for the preparation of the key fragments 5 and 6; (3) a highly regioselective Thiele-Winter acetoxylation step; and (4) a stereoselective Horner-Wadsworth-Emmons coupling reaction employing fragment 6 as a non-stabilized phosphonate as an effective partner. The metachromin-A synthesis was made formally enantioselective by the asymmetric synthesis of fragment 5 employing the methodologies developed by Simpkins (asymmetric deprotonation with a chiral nitrogenated base) and d?Angelo (enantioselective deracemization). This latter protocol furnished fragment 5 with an enantiomeric excess of ~85%, as determined by ¹H-NMR spectroscopy.

In the 2018 yellow fever (YF) outbreak in Brazil, we generated new transcriptomic data and combined it with clinical and immunological data to decode the pathogenesis of YF. Analyzing 79 patients, we found distinct gene expression patterns between acute YF, other viral infections, and the milder YF-17D vaccine infection. We identified a critical role for low-density, immature neutrophils in severe outcomes, marked by the downregulation of genes essential for neutrophil migration and maturation, such as PADI4, CSF3R, and ICAM1, in deceased patients. Our study also revealed complex interactions among inflammation-related genes, including increased CXCL10 and IL1R2 expression and decreased IL-1b expression in the acute phase. The diminished expression of HLA class II genes indicates impaired antigen presentation. These findings highlight the delicate balance of immune responses in YF pathogenesis and lay the groundwork for future therapeutic and diagnostic advancements., (© 2024 Wiley Periodicals LLC.)

In 2018 there was a large yellow fever outbreak in São Paulo, Brazil, with a high fatality rate. Yellow fever virus can cause, among other symptoms, hemorrhage and disseminated intravascular coagulation, indicating a role for endothelial cells in disease pathogenesis. Here, we conducted a case-control study and measured markers related to endothelial damage in plasma and its association with mortality. We found that angiopoietin 2 is strongly associated with a fatal outcome and could serve as a predictive marker for mortality. This could be used to monitor severe cases and provide care to improve disease outcome., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Cancer is a worldwide health problem with high mortality in children and adults, making searching for novel bioactive compounds with potential use in cancer treatment essential. Piplartine, also known as piperlongumine, is an alkamide isolated from Piper longum Linn, with relevant therapeutic potential. Therefore, this review covered research on the antitumor activity of piplartine, and the studies reported herein confirm the antitumor properties of piplartine and highlight its possible application as an anticancer agent against various types of tumors. The evidence found serves as a reference for advancing mechanistic research on this metabolite and preparing synthetic derivatives or analogs with better antitumor activity in order to develop new drug candidates.

Leishmaniasis, caused by protozoa of the genus Leishmania , encompasses a group of neglected diseases with diverse clinical and epidemiological manifestations that can be fatal if not adequately and promptly managed/treated. The current chemotherapy options for this disease are expensive, require invasive administration and often lead to severe side effects. In this regard, our research group has previously reported the potent anti- Leishmania activity of two coordination compounds (complexes) derived from 1,10-phenanthroline-5,6-dione (phendione): [Cu(phendione) 3 ].(ClO 4 ) 2 .4H 2 O and [Ag(phendione) 2 ].ClO 4 . The present study aimed to evaluate the effects of these complexes on leishmanolysin (gp63), a virulence factor produced by all Leishmania species that plays multiple functions and is recognized as a potential target for antiparasitic drugs. The results showed that both Ag-phendione (-74.82 kcal/mol) and Cu-phendione (-68.16 kcal/mol) were capable of interacting with the amino acids comprising the active site of the gp63 protein, exhibiting more favorable interaction energies compared to phendione alone (-39.75 kcal/mol) or 1,10-phenanthroline (-45.83 kcal/mol; a classical gp63 inhibitor) as judged by molecular docking assay. The analysis of kinetic parameters using the fluorogenic substrate Z-Phe-Arg-AMC indicated V max and apparent K m values of 0.064 µM/s and 14.18 µM, respectively, for the released gp63. The effects of both complexes on gp63 proteolytic activity were consistent with the in silico assay, where Ag-phendione exhibited the highest gp63 inhibition capacity against gp63, with an IC 50 value of 2.16 µM and the lowest inhibitory constant value (K i = 5.13 µM), followed by Cu-phendione (IC 50 = 163 µM and K i = 27.05 µM). Notably, pretreatment of live L. amazonensis promastigotes with the complexes resulted in a significant reduction in the expression of gp63 protein, including the isoforms located on the parasite cell surface. Both complexes markedly decreased the in vitro association indexes between L. amazonensis promastigotes and THP-1 human macrophages; however, this effect was reversed by the addition of soluble gp63 molecules to the interaction medium. Collectively, our findings highlight the potential use of these potent complexes in antivirulence therapy against Leishmania , offering new insights for the development of effective treatments for leishmaniasis.

Background: Yellow fever is a mosquito-borne zoonotic disease caused by yellow fever virus (YFV). Between 2017 and 2019, more than 504 human cases and 176 deaths were confirmed in the outskirts of São Paulo city. Throughout this outbreak, studies suggested a potential association between YFV viremia and mortality., Methods: Viral ribonucleic acid was measured using reverse-transcription quantitative polymerase chain reaction in plasma samples collected at up to 5 time points, between 3 and 120 days after symptoms onset., Results: Eighty-four patients with confirmed YFV infection were included. Most were males, median age was 42, and 30 (36%) died. Deceased patients were older than survivors (P = .003) and had a higher viremia across all time points (P = .0006). Mean values of viremia had a positive, statistically significant correlation with peak values of neutrophils, indirect bilirubin, aspartate transaminase, international normalized ratio, and creatinine. Finally, a Cox proportional hazards model adjusted for age and laboratory variables showed that viremia is independently associated with death, with a mean 1.84-fold increase (84%) in the hazard of death (P < .001) for each unit increase in mean log10 viremia., Conclusions: Our results raise the importance of monitoring YFV viremia and suggest a potential benefit of antiviral drugs or neutralizing monoclonal antibodies early in the course of this infection to improve disease outcomes., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The scientific community has been focusing on studying and understanding the extent of damage caused by microplastics (MPs) to flora, fauna, and humans, including the environmental and health risks associated with them. MPs with different morphologies have been described in different environments, with fibers being the most common type regardless of the environment. Various methods have been used to analyze MPs. Analytical methodologies such as visual inspection, spectroscopic methods, and others currently used to study MPs are time-consuming, and only subjective results are obtained when these methods are used for sample analysis. Researchers have used various dyes, such as Nile Red (NR), a selective fluorescent stain, to differentiate the polymers from the other sample components and address these problems. Using such dyes helps distinguish polymer particles from other contaminants present in the samples. We aimed to study the analytical process, morphology, and wettability of synthetic (such as polyethylene and polypropylene) and natural (such as linen and cotton) fibers using NR to characterize the fibers. The fibers were fragmented manually, and the samples were prepared using a cryomicrotome. The prepared samples were subjected to different NR incubation times of 30 min, 24 h, and 168 h, and characterized under ultraviolet light using optical microscopy. We investigated the effect of NR on different fibers, and the samples selection using the fluorescence properties generated when the fibers adsorbed the NR dye. The wettabilities of the samples indicated that polyethylene and polypropylene were hydrophobic, while linen and cotton were hydrophilic. Both synthetic and natural fibers exhibited fluorescence properties in the presence of NR. This increased the complexity of executing the MP characterization process, indicating that combined methodologies and optical and chemical identification processes should be used to characterize plastic specimens efficiently. We summarize and discuss the results and findings and provide recommendations for future laboratory research on microplastic fibers focusing on (I) microplastic selection, (II) stain preparation, and (III) microplastic characterization., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Coronavac is a widely used SARS-CoV-2 inactivated vaccine, but its long-term immune response assessment is still lacking. We evaluated SARS-CoV-2-specific immune responses, including T cell activation markers, antigen-specific cytokine production and antibody response following vaccination in 53 adult and elderly individuals participating in a phase 3 clinical trial. Activated follicular helper T (Tfh), non-Tfh and memory CD4 + T cells were detected in almost all subjects early after the first vaccine dose. Activated memory CD4 + T cells were predominantly of central and effector memory T cell phenotypes and were sustained for at least 6 months. We also detected a balanced Th1-, Th2- and Th17/Th22-type cytokine production that was associated with response over time, together with particular cytokine profile linked to poor responses in older vaccinees. SARS-CoV-2-specific IgG levels peaked 14 days after the second dose and were mostly stable over one year. CoronaVac was able to induce a potent and durable antiviral antigen-specific cellular response and the cytokine profiles related to the response over time and impacted by the senescence were defined., Competing Interests: Employees of Fundação Butantan and Instituto Butantan participated in the clinical trial design and data collection. Author AS is a consultant for Gritstone Bio, Flow Pharma, ImmunoScape, Moderna, AstraZeneca, Avalia, Fortress, Repertoire, Gilead, Gerson Lehrman Group, RiverVest, MedaCorp, and Guggenheim. The La Jolla Institute (LJI) has filed for patent protection for various aspects of T cell epitope and vaccine design work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Costa, Correia, Marmorato, Dias, Thomazella, Cabral da Silva, de Oliveira, Gusmão, Ferrari, Freitas, Patiño, Grifoni, Weiskopf, Sette, Scharf, Kallás and Silveira.)

Background: The Sinovac SARS-CoV-2 inactivated vaccine (CoronaVac) has been demonstrated to be safe, well tolerated, and efficacious in preventing mild and severe Covid-19. Although different studies have demonstrated its short-term immunogenicity, long-term cellular and humoral response evaluations are still lacking., Methods: Cellular and humoral responses were assessed after enrollment of volunteers in the PROFISCOV phase 3 double-blind, randomized, placebo-controlled clinical trial to evaluate CoronaVac. Assays were performed using flow cytometry to evaluate cellular immune response and an antigen binding electrochemiluminescence assay to detect antigen-specific antibodies to the virus., Results: Fifty-three volunteers were selected for long term assessment of their SARS-CoV-2-specific immune responses. CD4 + T cell responses (including circulating follicular helper (cTfh, CD45RA - CXCR5 + ) expressing CD40L, as well as non-cTfh cells expressing CXCR3) were observed early upon the first vaccine dose, increased after the second dose, remaining stable for 6-months. Memory CD4 + T cells were detected in almost all vaccinees, the majority being central memory T cells. IgG levels against Wuhan/WH04/2020 N, S and receptor binding domain (RBD) antigens and the variants of concern (VOCs, including B.1.1.7/Alpha, B.1.351/Beta and P.1/Gamma) S and RBD antigens peaked 14 days after the second vaccine shot, and were mostly stable for a 1-year period., Conclusions: CoronaVac two-doses regimen is able to induce a potent and durable SARS-CoV-2 specific cellular response. The cellular reaction is part of a coordinated immune response that includes high levels of specific IgG levels against parental and SARS-CoV-2 VOC strains, still detected after one year., Funding: Fundação Butantan, Instituto Butantan and São Paulo Research Foundation (FAPESP) (grants 2020/10127-1 and 2020/06409-1). This work has also been supported by NIH contract 75N93019C00065 (A.S, D.W). PATH facilitated reagent donations for this work with support by the Bill & Melinda Gates Foundation (INV-021239). Under the grant conditions of the foundation, a Creative Commons Attribution 4.0 generic License has already been assigned to the Author Accepted Manuscript version that might arise from this submission.

An effective vaccine against the dengue virus (DENV) should induce a balanced, long-lasting antibody (Ab) response against all four viral serotypes. The burst of plasmablasts in the peripheral blood after vaccination may reflect enriched vaccine-specific Ab secreting cells. Here we characterize the acute plasmablast responses from naïve and DENV-exposed individuals following immunization with the live attenuated tetravalent (LAT) Butantan DENV vaccine (Butantan-DV). The frequency of circulating plasmablasts was determined by flow cytometric analysis of fresh whole blood specimens collected from 40 participants enrolled in the Phase II Butantan-DV clinical trial (NCT01696422) before and after (days 6, 12, 15 and 22) vaccination. We observed a peak in the number of circulating plasmablast at day 15 after vaccination in both the DENV naïve and the DENV-exposed vaccinees. DENV-exposed vaccinees experienced a significantly higher plasmablast expansion. In the DENV-naïve vaccinees, plasmablasts persisted for approximately three weeks longer than among DENV-exposed volunteers. Our findings indicate that the Butantan-DV can induce plasmablast responses in both DENV-naïve and DENV-exposed individuals and demonstrate the influence of pre-existing DENV immunity on Butantan DV-induced B-cell responses., Competing Interests: JK and RP are former employees of the Butantan Institute. AP is an employee of the Butantan Institute. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer (CP) declared a shared affiliation with the author (MT) to the handling editor at the time of review., (Copyright © 2022 Silveira, Magnani, Costa, Avelino-Silva, Ricciardi, Timenetsky, Goulart, Correia, Marmorato, Ferrari, Nakagawa, Tomiyama, Tomiyama, Kalil, Palacios, Precioso, Watkins and Kallás.)

The resurgence of yellow fever in South America has prompted vaccination against the etiologic agent, yellow fever virus (YFV). Current vaccines are based on a live-attenuated YF-17D virus derived from a virulent African isolate. The capacity of these vaccines to induce neutralizing antibodies against the vaccine strain is used as a surrogate for protection. However, the sensitivity of genetically distinct South American strains to vaccine-induced antibodies is unknown. We show that antiviral potency of the polyclonal antibody response in vaccinees is attenuated against an emergent Brazilian strain. This reduction was attributable to amino acid changes at two sites in central domain II of the glycoprotein E, including multiple changes at the domain I-domain II hinge, which are unique to and shared among most South American YFV strains. Our findings call for a reevaluation of current approaches to YFV immunological surveillance in South America and suggest approaches for updating vaccines., Competing Interests: Declaration of interests K.C. is a member of the scientific advisory boards of Integrum Scientific, Biovaxys Technology, and the Pandemic Security Initiative of Celdara Medical. A.Z.W., M.S., and L.M.W. are/were employees of Adimab, and may hold shares in Adimab. L.M.W. is an employee of Adagio Therapeutics, and holds shares in Adagio Therapeutics. C.L.M. and Z.A.B. are employees of Mapp Biopharmaceutical., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Unmanned Aerial Vehicles (UAVs) have recently been used in a wide variety of applications due to their versatility, reduced cost, rapid deployment, among other advantages. Search and Rescue (SAR) is one of the most prominent areas for the employment of UAVs in place of a manned mission, especially because of its limitations on the costs, human resources, and mental and perception of the human operators. In this work, a real-time path-planning solution using multiple cooperative UAVs for SAR missions is proposed. The technique of Particle Swarm Optimization is used to solve a Model Predictive Control (MPC) problem that aims to perform search in a given area of interest, following the directive of international standards of SAR. A coordinated turn kinematic model for level flight in the presence of wind is included in the MPC. The solution is fully implemented to be embedded in the UAV on-board computer with DUNE, an on-board navigation software. The performance is evaluated using Ardupilot's Software-In-The-Loop with JSBSim flight dynamics model simulations. Results show that, when employing three UAVs, the group reaches 50% Probability of Success 2.35 times faster than when a single UAV is employed.

Campomanesia adamantium (Myrtaceae) is popularly known as "gabiroba" and has been used in folk medicine as antirheumatic, antidiarrheal, hypocholesterolemic and anti-inflammatory. This study evaluated the anti-inflammatory and antinociceptive activities and toxicology of essential oils from peel (EOP) and seed (EOS) of C. adamantium fruits in animal models. Different groups were treated with doses of 100 and 300 mg/kg and the inflammatory parameters were evaluated in carrageenan induced paw oedema and leukocyte migration in pleurisy model, while antinociceptive activity was evaluated using formalin method in rodents. The major constituent of EOP and EOS was limonene with 13.07% and 20.89%, respectively. No clinical signs of toxicity have been observed in animals. It was observed a significant decreased (P<0.01) in leukocyte migration at the dose of 300 mg/kg of EOP and EOS, with maximal inhibition of 89±3% for EOP and 80±6% for EOS. Paw oedema was inhibited at all times, and maximal inhibition was at the dose of 100 mg/kg at 2 h after carrageenan injection with 72±2% for EOP and 74±2% for EOS. EOS and EOP also reduced the first and second phases of formalin-induced nociception test. In the first formalin-phase, maximal inhibitions were at 48±5% for EOP and 66±4% for EOS (300 mg/kg). At the inflammatory phase induced by formalin, maximal inhibitions were 72±2% for EOP and 80±2% for EOS at the dose of 100 mg/kg. Seed and peel essential oils from C. adamantium fruit inhibited leukocyte migration, inflammatory and neurogenic pain and oedema suggesting their use as nutraceutical or pharmacological agent.

Protein malnutrition (PM) is a major public health problem in developing countries, affecting the inflammatory response and increasing susceptibility to opportunistic infections. For this reason, an adequate nutritional intervention can improve the quality of life of patients. Glutamine (GLN) is a nonessential amino acid, but can be considered "conditionally essential" for macrophage function in stress situations, in which it plays a role in the improvement of the inflammatory response. Concerning this issue, in the current study, it was of interest to evaluate some biological aspects of peritoneal cells from a protein malnutrition (PM) mouse model challenged with lipopolysaccharide (LPS) and treated intravenously with GLN. Two-month-old male Balb/c mice were subjected to a low-protein diet (2 % protein) and stimulated intravenously with LPS 1 h prior to the injection of 0.75 mg/kg GLN. Malnourished animals showed a reduced number of total peritoneal cells. Malnourished animals stimulated with LPS or LPS plus GLN did not show differences in peritoneal cell counts; however, the control group showed increased cellularity after LPS stimulus, which was reversed after GLN injection. Further, in the animals from both groups stimulated with LPS, GLN decreased the circulating levels of TNF-α and the levels of TNF-α produced by peritoneal cells; additionally, GLN decreased the IL-10 circulating levels in the malnourished animals stimulated with LPS. In addition, peritoneal cells of the control and malnourished groups stimulated with LPS showed a negative modulation of the NFkB signaling pathway after GLN injection. In conclusion, this study shows that GLN has the capacity to reduce TNF-α synthesis as well as to act as a negative regulator of NFkB phosphorylation, leading to a positive outcome in the control of TNF-α production.

Efavirenz is an essential medicine for the treatment of HIV, which is still inaccessible to millions of people worldwide. A novel, semi-continuous process provides rac-Efavirenz with an overall yield of 45%. This streamlined proof-of-principle synthesis relies on the efficient copper-catalyzed formation of an aryl isocyanate and a subsequent intramolecular cyclization to install the carbamate core of Efavirenz in one step. The three-step method represents the shortest synthesis of this life-saving drug to date., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: To determine the frequency of six mutations (F508del, G542X, G551D, R553X, R1162X, and N1303K) in patients with cystic fibrosis (CF) diagnosed, at a referral center, on the basis of abnormal results in two determinations of sweat sodium and chloride concentrations., Methods: This was a cross-sectional study involving 70 patients with CF. The mean age of the patients was 12.38 ± 9.00 years, 51.43% were female, and 94.29% were White. Mutation screening was performed with polymerase chain reaction (for F508del), followed by enzymatic digestion (for other mutations). Clinical analysis was performed on the basis of gender, age, ethnicity, pulmonary/gastrointestinal symptoms, and Shwachman-Kulczycki (SK) score., Results: All of the patients showed pulmonary symptoms, and 8 had no gastrointestinal symptoms. On the basis of the SK scores, CF was determined to be mild, moderate, and severe in 22 (42.3%), 17 (32.7%), and 13 (25.0%) of the patients, respectively. There was no association between F508del mutation and disease severity by SK score. Of the 140 alleles analyzed, F508del mutation was identified in 70 (50%). Other mutations (G542X, G551D, R553X, R1162X, and N1303K) were identified in 12 (7.93%) of the alleles studied. In F508del homozygous patients with severe disease, the OR was 0.124 (95% CI: 0.005-0.826)., Conclusions: In 50% of the alleles studied, the molecular diagnosis of CF was confirmed by identifying a single mutation (F508del). If we consider the analysis of the six most common mutations in the Brazilian population (including F508del), the molecular diagnosis was confirmed in 58.57% of the alleles studied.

Dietary supplementation of stearidonic acid (SDA; 18:4n-3) has been considered a possible strategy to increase n-3 unsaturated fatty acid content in ruminant products; however, little is known about its metabolism in the rumen. In vitro batch incubations were carried out with bovine ruminal digesta to investigate the metabolism of SDA and its biohydrogenation products. Incubation mixtures (4.5 mL) that contained 0 (control), 0.25, 0.50, 0.75, 1.00, 1.25, or 1.50 mg of SDA supplemented to 33 mg (DM basis) of commercial total mixed ration based on corn silage, for dairy cows, were incubated for 72 h at 39°C. The content of most fatty acids in whole freeze-dried cultures was affected by SDA supplementation. Branched-chain fatty acids decreased linearly (P < 0.01), and odd-chain fatty acids decreased quadratically (P < 0.01), particularly from 1.00 mg of SDA and above, whereas most C18 fatty acids increased linearly or quadratically (P ≤ 0.04). Stearidonic acid concentrations at 72 h of incubation were very small (<0.6% of total fatty acids and ≤0.9% of added SDA) in all treatments. The apparent biohydrogenation of SDA was extensive, but it was not affected by SDA concentration (P > 0.05). Biohydrogenation followed a pattern similar to that of other C18 unsaturated fatty acids up to 1.00 mg of SDA. Stearic acid (18:0) and vaccenic acid (18:1 trans-11) were the major fatty acids formed, with the latter increasing 9-fold in the 1.00 mg of SDA treatment. At greater inclusion rates, 18:0 and 18:1 trans isomers decreased (P ≤ 0.03), accompanied by increases in unidentified 18:3 and 18:4 isomers (P = 0.02), suggesting that the biohydrogenation pathway was inhibited. The present results clearly indicate that SDA was metabolized extensively, with numerous 18:4 and 18:3 products formed en route to further conversion to 18:2, 18:1 isomers, and 18:0.

An efficient rhodium(III)-catalyzed C-H activation and subsequent conjugate addition was achieved under mild conditions. The reaction utilized inert arenes to replace stoichiometric organometallic reagents and can tolerate various functional groups as well as air and water.

A palladium-catalyzed coupling of N-heterocycles with simple alcohols was achieved. The reaction is initiated by peroxide and does not require the use of stoichiometric acid for activation of the heterocycle.

Cardiovascular effects of Labd-8 (17)-en-15-oic acid (Labd-8), a labdenic diterpene isolated from methanolic extract of Moldenhawera nutans were investigated in normotensive rats. Additionally, this study examined the role of autonomic nervous system in the mediation of these cardiovascular effects. In pentobarbital-anesthetized rats, bolus intravenous (i.v.) injection of Labd-8 (1-10 mg/kg) induced dose-dependent hypotensive and tachycardiac responses. After cervical bivagotomy, hypotensive responses to Labd-8 were significantly enhanced whereas the tachycardia was completely abolished. In conscious rats, Labd-8 (1-10 mg/kg, i.v.) also decreased blood pressure and increased heart rate in a dose-dependent manner. Pretreatment with methylatropine (1 mg/kg, i.v.) or propranolol (2 mg/kg, i.v.) significantly reduced the tachycardia evoked by Labd-8 without affecting the hypotension. Blockade of ganglionic neurotransmission with hexamethonium (30 mg/kg, i.v.) reduced and abolished the hypotensive and tachycardic effects of Labd-8, respectively. However, hypotensive effects of Labd-8 were not reduced by pretreatment with N(w)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg, i.v.), a nitric oxide synthase inhibitor. In rat endothelium-containing aorta preparations, Labd-8 (1-1000 micro g/ml) induced a concentration-dependent reduction of potassium (60 mM)-induced contraction [IC(50) (geometric mean +/-95% confidence interval)=313.6 (191.4-513.8) micro g/ml], an effect that remained unaffected [IC(50)=440.8 (225.1-863.3) micro g/ml] by removal of vascular endothelium. These results show that i.v. treatment with Labd-8-induced dose-dependent hypotensive and tachycardiac effects in both conscious and anesthetized rats. The tachycardia is mediated reflexly through inhibition of vagal and activation of sympathetic drive to the heart. The hypotension is mainly due to withdrawal of sympathetic tone to the vasculature and also partly to an active vascular relaxation. Released nitric oxide from vascular endothelial cells is not involved in the mediation of Labd-8-induced hypotension.

Objective: To identify factors associated with increased arterial blood pressure in children., Methods: In this cross-sectional study, arterial blood pressure was measured in 672 children between 2 and 11 years of age from two schools in the city of Belo Horizonte, Brazil. After providing informed consent, all children had their blood pressure and anthropometric parameters measured. Blood pressure was measured based on the recommendations of the Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents. The following variables were assessed: age, sex, race, urban life quality index, weight, height, and body mass index. Analysis of variance was used for comparison of means and the chi-square was used for comparison of proportions. Variables associated with increased blood pressure were included in a multiple regression model., Results: According to univariate analysis, increased systolic and diastolic blood pressure were associated with high urban life quality index, white race and high body mass index. On multivariate analysis, body mass index, urban life quality index and height remained associated with increased systolic blood pressure; urban life quality index and age were associated with increased diastolic blood pressure., Conclusion: In this study, excess weight and obesity were associated with increased systolic blood pressure. Other unidentified factors were partially associated with increased blood pressure in children from the school with elevated urban life quality index.

A well-characterised collagen-glycosaminoglycan (CG) matrix functions as an extracellular matrix analogue (ECMA) of dermis on full-thickness wounds. The epidermis can be reconstituted by seeding autologous uncultured keratinocytes into the matrix prior to grafting. We hypothesised that seeding the CG matrix with keratinocytes cultured to sub-confluence may provide the ECMA with more proliferating keratinocytes than with uncultured keratinocytes. Autologous cells were isolated from split-thickness skin grafts and cultured to sub-confluence. ECMAs were seeded by centrifuging cultured (n = 8) or uncultured (n = 8) autologous keratinocytes into a CG matrix at a density of 100,000 cells/cm2, then applied onto full-thickness wounds on Yorkshire pigs. Gross and histologic observations were made up to 21 days post-grafting. At 14 days, a fully differentiated epidermis was present on all graft sites, but the epidermis of the cultured-cell-seeded matrices was thicker, 180 (19) microns, than the uncultured-cell-seeded matrices, 110 (18) microns. The epidermis of cultured-cell-seeded matrices was acanthotic, containing 14 (4) cell layers, as compared to uncultured-cell-seeded matrices, 9 (1) cell layers. The number of subepithelial keratinocyte cysts/cm cross-section present in the neodermis was also greater in cultured-, 1.35 (0.37), than in uncultured-cell-seeded matrices, 0.47 (0.35). Epidermal confluence on day 14 was 96 (3)% on cultured-cell-seeded grafts and 50 (17)% on uncultured-cell-seeded grafts. These results are consistent with the hypothesis that the process of in vitro cell cultivation increases the proportion of dividing cells in preference to differentiated cells. This technology may be useful in reconstruction of specialised bilayer tissues with minimal donor sites.