Enantioselective Synthesis of Dihydrobenzofurans, Dihydrobenzosulfones, and Dihydroindoles by Merging One-pot Intramolecular Heck-Matsuda Reactions from Anilines with Redox-Relay Process.

A one-pot tandem process was developed aiming at the concise and expeditious enantioselective synthesis of dihydrobenzofuran, dihydrobenzosulfone, and dihydroindole scaffolds under mild, and open-flask conditions. This process combines the in situ generation of aryldiazonium salt directly from the anilines in methanol telescoped to an intramolecular Heck-Matsuda reaction linked to a redox relay process to provide the final products as the dimethyl acetals. These Heck products were smoothly converted into the corresponding primary alcohols or esters. The robustness and the efficiency of the protocol are demonstrated by the synthesis of 24 enantioenriched dihydrobenzofurans, dihydrobenzosulfones, and dihydroindoles in overall yields up to 78% in enantiomeric ratios up to 99:1 by a sequential 5-step protocol..

Enantioselective synthesis of ß-aryl-γ-lactam derivatives via Heck-Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles.

We report herein an enantioselective palladium-catalyzed Heck-Matsuda reaction for the desymmetrization of N-protected 2,5-dihydro-1H-pyrroles with aryldiazonium salts, using the chiral N,N-ligand (S)-PyraBox. This strategy has allowed straightforward access to a diversity of 4-aryl-γ-lactams via Heck arylation followed by a sequential Jones oxidation. The overall method displays a broad scope and good enantioselectivity, favoring the (R) enantiomer. The applicability of the protocol is highlighted by the efficient enantioselective syntheses of the selective phosphodiesterase-4-inhibitor rolipram and the commercial drug baclofen as hydrochloride.

Phasing segmented telescopes via deep learning methods: application to a deployable CubeSat.

Capturing high-resolution imagery of the Earth's surface often calls for a telescope of considerable size, even from low Earth orbits (LEOs). A large aperture often requires large and expensive platforms. For instance, achieving a resolution of 1 m at visible wavelengths from LEO typically requires an aperture diameter of at least 30 cm. Additionally, ensuring high revisit times often prompts the use of multiple satellites. In light of these challenges, a small, segmented, deployable CubeSat telescope was recently proposed creating the additional need of phasing the telescope's mirrors. Phasing methods on compact platforms are constrained by the limited volume and power available, excluding solutions that rely on dedicated hardware or demand substantial computational resources. Neural networks (NNs) are known for their computationally efficient inference and reduced onboard requirements. Therefore, we developed a NN-based method to measure co-phasing errors inherent to a deployable telescope. The proposed technique demonstrates its ability to detect phasing errors at the targeted performance level [typically a wavefront error (WFE) below 15 nm RMS for a visible imager operating at the diffraction limit] using a point source. The robustness of the NN method is verified in presence of high-order aberrations or noise and the results are compared against existing state-of-the-art techniques. The developed NN model ensures its feasibility and provides a realistic pathway towards achieving diffraction-limited images.

First Description of Marinoquinoline Derivatives' Activity against Toxoplasma gondii.

Toxoplasmosis is a globally prevalent zoonotic disease with significant clinical implications, including neurotoxoplasmosis, a leading cause of cerebral lesions in AIDS patients. The current pharmacological treatments for toxoplasmosis face clinical limitations, necessitating the urgent development of new therapeutics. Natural sources have yielded diverse bioactive compounds, serving as the foundation for clinically used derivatives. The exploration of marine bacteria-derived natural products has led to marinoquinolines, which feature a pyrroloquinoline core and demonstrate in vitro and in vivo anti-Plasmodium activity. This study investigates the in vitro anti-Toxoplasma gondii potential of six marinoquinoline derivatives. Additionally, it conducts absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions, and evaluates the in vivo efficacy of one selected compound. The compounds displayed half-maximal effective concentration (EC50) values between 1.31 and 3.78 µM and half-maximal cytotoxic concentration (CC50) values ranging from 4.16 to 30.51 µM, resulting in selectivity indices (SI) from 3.18 to 20.85. MQ-1 exhibiting the highest in vitro SI, significantly reduced tachyzoite numbers in the peritoneum of RH-infected Swiss mice when it was orally administered at 12.5 mg/kg/day for eight consecutive days. Also, MQ-1 significantly reduced the cerebral parasite burden in chronically ME49 infected C57BL/6 mice when it was orally administered at 25 mg/kg/day for 10 consecutive days. These findings underscore the promising anti-T. gondii activity of marinoquinolines and their potential as novel therapeutic agents against this disease.

Autologous cell immunotherapy (IGV-001) with IGF-1R antisense oligonucleotide in newly diagnosed glioblastoma patients.

Standard-of-care first-line therapy for patients with newly diagnosed glioblastoma (ndGBM) is maximal safe surgical resection, then concurrent radiotherapy and temozolomide, followed by maintenance temozolomide. IGV-001, the first product of the Goldspire™ platform, is a first-in-class autologous immunotherapeutic product that combines personalized whole tumor-derived cells with an antisense oligonucleotide (IMV-001) in implantable biodiffusion chambers, with the intent to induce a tumor-specific immune response in patients with ndGBM. Here, we describe the design and rationale of a randomized, double-blind, phase IIb trial evaluating IGV-001 compared with placebo, both followed by standard-of-care treatment in patients with ndGBM. The primary end point is progression-free survival, and key secondary end points include overall survival and safety.

Glioblastoma (GBM) is a fast-growing brain tumor that happens in about half of all gliomas. Surgery is the first treatment for patients with newly diagnosed GBM, followed by the usual radiation and chemotherapy pills named temozolomide. Temozolomide pills are then given as a long-term treatment. The outcome for the patient with newly diagnosed GBM remains poor. IGV-001 is specially made for each patient. The tumor cells are removed during surgery and mixed in the laboratory with a small DNA, IMV-001. This mix is the IGV-001 therapy that is designed to give antitumor immunity against GBM. IGV-001 is put into small biodiffusion chambers that are irradiated to stop the growth of any tumor cells in the chambers. In the phase IIb study, patients with newly diagnosed GBM are chosen and assigned to either the IGV-001 or the placebo group. A placebo does not contain any active ingredients. The small biodiffusion chambers containing either IGV-001 or placebo are surgically placed into the belly for 48 to 52 h and then removed. Patients then receive the usual radiation and chemotherapy treatment. Patients must be adults aged between 18 and 70 years. Patients also should be able to care for themselves overall, but may be unable to work or have lower ability to function. Patients with tumors on both sides of the brain are not eligible. The main point of this study is to see if IGV-001 helps patients live longer without making the illness worse compared with placebo. Clinical Trial Registration: NCT04485949 (ClinicalTrials.gov).

On Sandy, Boron-Poor Soils, Liming Induced Severe Boron Deficiency and Drastically Reduced the Dry Matter Yield of Young Olive Trees.

In the northeast of Portugal, like in many parts of the world, most soils are acidic, which may hamper crop productivity. This study presents the findings of a factorial experiment on olive (Olea europaea L.) involving three factors: (i) soil type [schist (Sch) and granite (Gra)]; (ii) cultivars [Cobrançosa (Cob) and Arbequina (Arb)]; and (iii) fertilizer treatments [liming (CaCO3) plus magnesium (Mg) (LMg), phosphorus (P) application (+P), boron (B) application (+B), all fertilizing materials combined (Con+), and an untreated control (Con-)]. Dry matter yield (DMY) did not show significant differences between cultivars, but plants grown in schist soil exhibited significantly higher biomass compared to those in granite soil. Among the treatments, +B and Con+ resulted in the highest DMY (50.8 and 47.2 g pot-1, respectively), followed by +P (34.3 g pot-1) and Con- (28.6 g pot-1). Treatment LMg yielded significantly lower values (15.6 g pot-1) than Con-. LMg raised the pH above 7 (7.36), leading to a severe B deficiency. Although Con+ also raised the pH above 7 (7.48), it ranked among the most productive treatments for providing B. Therefore, when applying lime to B-poor sandy soils, moderate rates are advised to avoid inducing a B deficiency. Additionally, it seems prudent to apply B after lime application.

Leptomeningeal disease in histone-mutant gliomas.

Background: The 2016 WHO classification described a subtype of midline gliomas harboring histone 3 (H3) K27M alterations, and the 2021 edition added a new subtype of hemispheric diffuse gliomas with H3 G34R/V mutations. The incidence and clinical behavior of leptomeningeal disease (LMD) in these patients is not well defined. Methods: Retrospective study of patients with H3-altered gliomas diagnosed from 01/2012 to 08/2021; histone mutations were identified through next-generation sequencing (NGS) of tumor biopsy and/or cerebrospinal fluid (CSF). Results: We identified 42 patients harboring H3 mutations (K27M mutations in 33 patients, G34R/V in 8, and both in one). Median age was 21 (4-70); 27 were male. LMD was diagnosed in 21/42 (50%) patients, corresponding to a 3-year cumulative incidence of 44.7% (95% confidence interval (CI): 26.1%-63.4%) for the K27-mutant group and a 1-year cumulative incidence of 37.5% in the G34-mutant group (95% CI: 0.01%-74.4%; no events after 1 year). Median time from tumor diagnosis to LMD was 12.9 months for H3-K27 patients and 5.6 months for H3-G34 patients. H3 mutation was detected in CSF in all patients with LMD who had NGS (8 H3-K27-mutant patients). In the H3-K27-mutant group, modeled risk of death was increased in patients who developed LMD (hazard ratio: 7.37, 95% CI: 2.98-18.23, P < .0001). Conclusions: In our cohort, 50% of patients developed LMD. Although further studies are needed, CSF ctDNA characterization may aid in identifying molecular tumor profiles in glioma patients with LMD, and neuroaxis imaging and CSF NGS should be considered for early LMD detection.

Impact of delaying botulinum toxin treatment in patients with migraine during the COVID-19 pandemic.

BACKGROUND: Due to coronavirus disease 2019 (COVID-19) pandemic response measures, the administration of botulinum toxin (BTX) was delayed for many patients during the first lockdown period in Portugal. OBJECTIVES: To review the impact of postponing BTX treatment on migraine control. METHODS: This was a retrospective, single-center study. Patients with chronic migraine who had done at least three previous BTX cycles and were considered responders were included. The patients were divided into two groups, one that has had their treatment delayed (group P), and one that has not (controls). The Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) protocol was used. Migraine-related data were obtained at baseline and at three subsequent visits. RESULTS: The present study included two groups, group P (n = 30; 47.0 ± 14.5 years; 27 females, interval baseline -1st visit: 5.5 [4.1-5.8] months) and the control group (n = 6; 57.7 ± 13.2 years; 6 females; interval baseline-1st visit 3.0 [3.0-3.2] months). No difference between the groups was present at baseline. When compared to baseline, the number of days/month with migraine (5 [3-6.2] vs. 8 [6-15] p < 0.001), days using triptans/month (2.5 [0-6] vs. 3 [0-8], p = 0.027) and intensity of pain (7 [5.8-10] vs. 9 [7-10], p = 0.012) were greater in the first visit for group P, while controls did not present a significant variation. The worsening of migraine-related indicators decreased in the following visits; however, even in the third visit, it had not returned to baseline. Correlations were significant between the delayed time to treatment and the increase in days/month with migraines at the first visit after lockdown (r = 0.507; p = 0.004). CONCLUSIONS: There was a deterioration of migraine control after postponed treatments, with a direct correlation between the worsening of symptoms and the number of months that the treatment was delayed.

ANTECEDENTES: Devido às medidas de resposta à pandemia de coronavirus disease 2019 (covid-19), a administração de toxina botulínica (TXB) foi adiada para muitos pacientes durante o primeiro confinamento em Portugal. OBJETIVOS: Avaliar o impacto do adiamento do tratamento com TXB no controle da enxaqueca. MéTODOS: Estudo retrospectivo unicêntrico. Foram incluídos pacientes com enxaqueca crônica com pelo menos três ciclos prévios de TXB e que tenham sido considerados respondedores. Os pacientes foram divididos em dois grupos, sendo um com atraso do tratamento (grupo P) e outro sem atraso (controles). O protocolo Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) foi utilizado. Dados clínicos relacionados com a enxaqueca foram obtidos na consulta inicial (T0) e nas três consultas subsequentes (T1­3). RESULTADOS: O presente estudo incluiu dois grupos, o grupo P (n = 30; 47,0 ± 14,5 anos; 27 mulheres, intervalo T0-1ª visita: 5,5 [4,1­5,8] meses) e o grupo controle (n = 6; 57,7 ± 13,2 anos; 6 mulheres; intervalo T0­1ª visita 3,0 [3,0­3,2] meses). Os grupos não apresentavam nenhuma diferença no início do estudo. Quando comparado à T0, o número de dias/mês com enxaqueca (5 [3­6,2] vs. 8 [6­15], p < 0,001), dias usando triptanos/mês (2,5 [0­6] vs. 3 [0­8], p = 0,027) e intensidade da dor (7 [5,8­10] vs. 9 [7­10], p = 0,012) foram maiores na primeira visita no grupo P, não apresentando os controles variação significativa. A piora dos indicadores relacionados com a enxaqueca diminuiu nas visitas seguintes; porém, mesmo na terceira visita, ainda não haviam retornado ao basal. As correlações foram significativas entre o atraso do tratamento e o aumento de dias/mês com enxaqueca na primeira consulta após o confinamento (r = 0,507; p = 0,004). CONCLUSãO: Houve piora clínica da enxaqueca após o adiamento do tratamento em correlação direta com a duração do atraso.

Phase-Resolved Optical Coherence Elastography: An Insight into Tissue Displacement Estimation.

Robust methods to compute tissue displacements in optical coherence elastography (OCE) data are paramount, as they play a significant role in the accuracy of tissue elastic properties estimation. In this study, the accuracy of different phase estimators was evaluated on simulated OCE data, where the displacements can be accurately set, and on real data. Displacement (∆d) estimates were computed from (i) the original interferogram data (Δφori) and two phase-invariant mathematical manipulations of the interferogram: (ii) its first-order derivative (Δφd) and (iii) its integral (Δφint). We observed a dependence of the phase difference estimation accuracy on the initial depth location of the scatterer and the magnitude of the tissue displacement. However, by combining the three phase-difference estimates (Δdav), the error in phase difference estimation could be minimized. By using Δdav, the median root-mean-square error associated with displacement prediction in simulated OCE data was reduced by 85% and 70% in data with and without noise, respectively, in relation to the traditional estimate. Furthermore, a modest improvement in the minimum detectable displacement in real OCE data was also observed, particularly in data with low signal-to-noise ratios. The feasibility of using Δdav to estimate agarose phantoms' Young's modulus is illustrated.

Different LED light intensity and quality change perennial ryegrass (Lolium perenne L.) physiological and growth responses and water and energy consumption.

Light intensity and spectral composition highly affect plant physiology, growth, and development. According to growing conditions, each species and/or cultivar has an optimum light intensity to drive photosynthesis, and different light spectra trigger photosynthetic responses and regulate plant development differently. For the maintenance of natural sports pitches, namely professional football competitions, turf quality is a key condition. Due to the architecture of most football stadiums, the lawns receive low intensities of natural light, so supplementary artificial lighting above the turf is required. The use of light-emitting diodes (LEDs) can have a higher cost-benefit ratio than traditional high-pressure sodium lamps. The continuous emission spectrum, combined with high spectral selectivity and adjustable optical power, can be used to optimize plant growth and development. Thus, perennial ryegrass (Lolium perenne L.) plants, commonly used for lawns, were primarily grown at three different intensities (200, 300, and 400 µmol m-2 s-1) of cool white light. Despite the higher water and energy consumption, 400 µmol m-2 s-1 maximizes the plant's efficiency, with higher photosynthetic rates and foliar pigment concentration, and more foliar soluble sugars and aboveground biomass accumulation. Then, it was evaluated the perennial ryegrass (Double and Capri cultivars) response to different spectral compositions [100% cool white (W), 80% Red:20% Blue (R80:B20), 90% Red:10% Blue (R90:B10), and 65% Red:15% Green:20% Blue (R65:G15:B20)] at 400 µmol m-2 s-1. Both cultivars exhibited similar responses to light treatments. In general, W contributed to the better photosynthetic performance and R90:B10 to the worst one. Water consumption and aboveground biomass were equal in all light treatments. R80:B20 allows energy savings of 24.3% in relation to the W treatment, showing a good compromise between physiological performance and energy consumption.

Combining Zeolites with Early-Maturing Annual Legume Cover Crops in Rainfed Orchards: Effects on Yield, Fatty Acid Composition and Polyphenolic Profile of Olives and Olive Oil.

Under climate change threats, there is a growing need to adapt the conventional agronomic practices used in rainfed olive orchards by sustainable practices, in order to ensure adequate crop yield and olive oil quality and to preserve soil health. Therefore, for two years, the effects of conventional tillage practice (T) and two sustainable soil management strategies, a leguminous cover crop (LC) and its combination with natural zeolites (ZL), on the yield, fatty acid composition, polyphenolic profile and quality indices of olive fruits and oil were evaluated. Crop yield was significantly increased by LC and ZL in the first year. Although in the second year no significant differences were verified, the cumulative yield increased significantly by 31.6% and 35.5% in LC and ZL trees, respectively. LC enhanced the moisture and size of olives, while ZL increased, in general, the concentrations of oleuropein, verbascoside, caffeic acid and epicatechin, as well the oleic/linoleic ratio in fruits and the levels of 3,4-dihydroxyphenylglycol, tyrosol, verbascoside and caffeic acid in olive oil. Despite the higher concentration of total phenols in the fruits and oil from T trees in the warmer and dryer year, the quality of the oil decreased, mainly when compared with ZL, as evidenced by the peroxide value and K232 and K270 coefficients. In short, both sustainable soil management strategies appear to be promising practices to implement in olive orchards under rainfed conditions, but the innovative strategy of combining zeolites with legume cover crops, first reported in the present study, confers advantages from a nutritional and technological point of view. Nevertheless, studies subjected to the long-term use of these practices should be conducted to ensure the sustainability of the crop yield and olive oil quality.

Impact of delaying botulinum toxin treatment in patients with migraine during the COVID-19 pandemic / O impacto do atraso no tratamento com toxina botulínica em pacientes com enxaqueca no contexto da pandemia da COVID-19

Abstract Background Due to coronavirus disease 2019 (COVID-19) pandemic response measures, the administration of botulinum toxin (BTX) was delayed for many patients during the first lockdown period in Portugal. Objectives To review the impact of postponing BTX treatment on migraine control. Methods This was a retrospective, single-center study. Patients with chronic migraine who had done at least three previous BTX cycles and were considered responders were included. The patients were divided into two groups, one that has had their treatment delayed (group P), and one that has not (controls). The Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) protocol was used. Migraine-related data were obtained at baseline and at three subsequent visits. Results The present study included two groups, group P (n = 30; 47.0 ± 14.5 years; 27 females, interval baseline -1st visit: 5.5 [4.1-5.8] months) and the control group (n = 6; 57.7 ± 13.2 years; 6 females; interval baseline-1st visit 3.0 [3.0-3.2] months). No difference between the groups was present at baseline. When compared to baseline, the number of days/month with migraine (5 [3-6.2] vs. 8 [6-15] p < 0.001), days using triptans/month (2.5 [0-6] vs. 3 [0-8], p = 0.027) and intensity of pain (7 [5.8-10] vs. 9 [7-10], p = 0.012) were greater in the first visit for group P, while controls did not present a significant variation. The worsening of migraine-related indicators decreased in the following visits; however, even in the third visit, it had not returned to baseline. Correlations were significant between the delayed time to treatment and the increase in days/month with migraines at the first visit after lockdown (r = 0.507; p = 0.004). Conclusions There was a deterioration of migraine control after postponed treatments, with a direct correlation between the worsening of symptoms and the number of months that the treatment was delayed.

Resumo Antecedentes Devido às medidas de resposta à pandemia de coronavirus disease 2019 (covid-19), a administração de toxina botulínica (TXB) foi adiada para muitos pacientes durante o primeiro confinamento em Portugal. Objetivos Avaliar o impacto do adiamento do tratamento com TXB no controle da enxaqueca. Métodos Estudo retrospectivo unicêntrico. Foram incluídos pacientes com enxaqueca crônica com pelo menos três ciclos prévios de TXB e que tenham sido considerados respondedores. Os pacientes foram divididos em dois grupos, sendo um com atraso do tratamento (grupo P) e outro sem atraso (controles). O protocolo Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) foi utilizado. Dados clínicos relacionados com a enxaqueca foram obtidos na consulta inicial (T0) e nas três consultas subsequentes (T1-3). Resultados O presente estudo incluiu dois grupos, o grupo P (n = 30; 47,0 ± 14,5 anos; 27 mulheres, intervalo T0-1ª visita: 5,5 [4,1-5,8] meses) e o grupo controle (n = 6; 57,7 ± 13,2 anos; 6 mulheres; intervalo T0-1ª visita 3,0 [3,0-3,2] meses). Os grupos não apresentavam nenhuma diferença no início do estudo. Quando comparado à T0, o número de dias/mês com enxaqueca (5 [3-6,2] vs. 8 [6-15], p < 0,001), dias usando triptanos/mês (2,5 [0-6] vs. 3 [0-8], p = 0,027) e intensidade da dor (7 [5,8-10] vs. 9 [7-10], p = 0,012) foram maiores na primeira visita no grupo P, não apresentando os controles variação significativa. A piora dos indicadores relacionados com a enxaqueca diminuiu nas visitas seguintes; porém, mesmo na terceira visita, ainda não haviam retornado ao basal. As correlações foram significativas entre o atraso do tratamento e o aumento de dias/mês com enxaqueca na primeira consulta após o confinamento (r = 0,507; p = 0,004). Conclusão Houve piora clínica da enxaqueca após o adiamento do tratamento em correlação direta com a duração do atraso.

Olive Yield and Physicochemical Properties of Olives and Oil in Response to Nutrient Application under Rainfed Conditions.

The effects of mineral fertilizers on the physicochemical properties of olives and oil under rainfed conditions is scarce. In this three-year study, the results of a nitrogen (N), phosphorus (P), potassium (K) and boron (B) fertilization trial carried out in a young rainfed olive grove and arranged as a nutrient omission trial are reported. The control consisted of the application of N, P, K and B (NPKB) and four other treatments corresponded to the removal of one of them (N0, P0, K0 and B0). Olive yield and several variables associated with the physicochemical properties of olives and oil were evaluated. The NPKB treatment increased olive yield compared to the treatment that did not receive N (N0). Although dependent on the climate conditions of the crop season, the NPKB treatment increased fruit weight and the pulp/pit ratio and its fruits tended to accumulate more oil than K0. However, the phenolics concentrations on fruits and oil tended to be lower. All olive oil samples were classified in the "extra virgin" category and all showed a decrease in its stability between 3 and 15 months of storage, regardless of treatment, especially in N0, P0 and B0 treatments. The results of the sensorial analysis indicate that all the oils fell into the medium fruitiness and greenly-fruity category. Only in P0 and B0 were defects detected, namely muddy sediment. Thus, this study seems to indicate the importance of N application, but also a balanced nutrient application and that further studies are needed, given the difficulty in finding clear trends in the response of measured variables to fertilizer treatments.

Hemothorax After Retroclavicular Approach to the Infraclavicular Region in a Critically Ill Patient: A Case Report.

The retroclavicular approach to the infraclavicular region (RAPTIR) is a recently described locoregional technique for upper limb analgesia that offers advantages over the classic infraclavicular block. RAPTIR is considered an effective and easy-to-perform block associated with few complications and better patient comfort. We present a case of a critically ill patient with thoracic and upper limb trauma. Despite multimodal analgesia, the patient developed delirium and experienced suboptimal pain control. An ultrasound-guided continuous RAPTIR block was performed, resulting in improved pain scores and delirium control. Twenty-four hours post block, the patient presented with dyspnea and chest pain, leading to the diagnosis of hemothorax. Chest computed tomography angiography revealed no vascular damage. The perineural catheter was removed 48 hours after its placement and the patient had a satisfactory recovery without long-term complications. The RAPTIR requires the needle to pass underneath the clavicle's acoustic shadow, putting the structures beneath the clavicle at risk of injury. Cadaver studies have raised concerns about potential vascular complications of the RAPTIR in a noncompressible location. This case highlights, for the first time, a rare but serious complication of the RAPTIR, demonstrating the potential risks of passing the needle through a blind spot.

Zeolites and Biochar Modulate Olive Fruit and Oil Polyphenolic Profile.

Soil degradation processes and climate change threaten the sustainability of Mediterranean rainfed olive orchards, with repercussions on crop yield and quality of olives, olive oil and olive by-products. Using soil amendments can enhance soil fertility for sustained environmental quality and plant performance. For two years, we evaluated, under rainfed conditions, the effects of a fertilizer compound (FC) and its combination with zeolites (ZL) and biochar (BC) amendments on soil moisture, yield, fruit and oil polyphenols and quality indices. The polyphenolic composition was strongly influenced by treatments, although no effects were observed on crop yield. ZL improved soil moisture (average increase of 26.3% compared to FC), fruit fatty acid composition (increase of 12.4% in oleic/linoleic ratio in 2018) and oil quality, BC enhanced the concentrations of polyphenols with high nutritional value (average annual increase of 25.6, 84.8 and 11.6% for 3,4-dihydroxyphenylglycol, oleuropein and rutin, respectively). In contrast, olive oil from FC fruits showed the poorest quality, with oxidation and hydrolytic breakdown signals. The applied soil amendments appear to be a promising sustainable strategy to implement in olive rainfed orchards.

Methyl Esters of (E)-Cinnamic Acid: Activity against the Plant-Parasitic Nematode Meloidogyne incognita and In Silico Interaction with Histone Deacetylase.

(E)-Cinnamaldehyde is very active against Meloidogyne incognita but has low persistence in soil. To circumvent this problem, esters of cinnamic acid were evaluated as a substitute for (E)-cinnamaldehyde. The best results under assays with M. incognita second-stage juveniles (J2) were obtained for the methyl esters of (E)-p-fluoro- (13), (E)-p-chloro- (14), and (E)-p-bromocinnamic acid (15), which showed lethal concentrations to 50% (LC50) J2 of 168, 95, and 216 µg/mL, respectively. Under the same conditions, the LC50 values for the nematicides carbofuran and fluensulfone were 160 and 34 µg/mL, respectively. Substances 13-15 were also active against nematode eggs, which account for most of the M. incognita population in the field. According to an in silico study, substances 13-15 can act against the nematode through inhibition of histone deacetylase. Therefore, esters 13-15 and histone deacetylase are potentially useful for the rational design of new nematicides for the control of M. incognita.

Pd-Catalyzed Dynamic Kinetic Asymmetric Cross-Coupling of Heterobiaryl Bromides with N-Tosylhydrazones.

A dynamic kinetic asymmetric Pd-catalyzed cross-coupling reaction of heterobiaryl bromides with ketone N-tosylhydrazones for the synthesis of heterobiaryl styrenes is described. The combination of Pd(dba)2 as a precatalyst with a TADDOL-derived phosphoramidite ligand provides the corresponding coupling products in good yields and high enantioselectivities under mild conditions. Racemization-free N-oxidation and N-alkylation of the products allowed us to obtain appealing functionalized axially chiral heterobiaryl derivatives.

Discovery of 3H-pyrrolo[2,3-c]quinolines with activity against Mycobacterium tuberculosis by allosteric inhibition of the glutamate-5-kinase enzyme.

The therapeutic potential of 3H-pyrrolo[2,3-c]quinolines-the main core of Marinoquinoline natural products-has been explored for the development of new anti-TB agents. The chemical modification of various positions in this scaffold has led to the discovery of two pyrroloquinolines (compounds 50 and 54) with good in vitro activity against virulent strains of Mycobacterium tuberculosis (H37Rv, MIC = 4.1 µM and 4.2 µM, respectively). Enzymatic assays showed that both derivatives are inhibitors of glutamate-5-kinase (G5K, encoded by proB gene), an essential enzyme for this pathogen involved in the first step of the proline biosynthesis pathway. G5K catalyzes the phosphoryl-transference of the γ-phosphate group of ATP to L-glutamate to provide L-glutamyl-5-phosphate and ADP, and also regulates the synthesis of L-proline. The results of various molecular dynamics simulation studies revealed that the inhibition of G5K would be caused by allosteric interaction of these compounds with the interface between enzyme domains, against different pockets and with distinct recognition patterns. The binding of compound 54 promotes long-distance conformational changes at the L-glutamate binding site that would prevent it from anchoring for catalysis, while compound 50 alters the ATP binding site architecture for recognition. Enzyme assays revealed that compound 50 caused a substancial increase in the Kmapp for ATP, while no significant effect was observed for derivative 54. This work also demonstrates the potential of the G5K enzyme as a biological target for the development of new anti-TB drugs.

Comprehensive Direct Georeferencing of Aerial Images for Unmanned Aerial Systems Applications.

Optical image sensors are the most common remote sensing data acquisition devices present in Unmanned Aerial Systems (UAS). In this context, assigning a location in a geographic frame of reference to the acquired image is a necessary task in the majority of the applications. This process is denominated direct georeferencing when ground control points are not used. Despite it applies simple mathematical fundamentals, the complete direct georeferencing process involves much information, such as camera sensor characteristics, mounting measurements, attitude and position of the UAS, among others. In addition, there are many rotations and translations between the different reference frames, among many other details, which makes the whole process a considerable complex operation. Another problem is that manufacturers and software tools may use different reference frames posing additional difficulty when implementing the direct georeferencing. As this information is spread among many sources, researchers may face difficulties on having a complete vision of the method. In fact, there is absolutely no paper in the literature that explain this process in a comprehensive way. In order to supply this implicit demand, this paper presents a comprehensive method for direct georeferencing of aerial images acquired by cameras mounted on UAS, where all required information, mathematical operations and implementation steps are explained in detail. Finally, in order to show the practical use of the method and to prove its accuracy, both simulated and real flights were performed, where objects of the acquired images were georeferenced.

Grey and Black Anti-Hail Nets Ameliorated Apple (Malus × domestica Borkh. cv. Golden Delicious) Physiology under Mediterranean Climate.

The use of anti-hail nets on orchards changes the microclimate underneath the net. This might be of great importance in apple growing regions characterized by high radiation levels and hot and dry climates during the summer season. But, depending on the net colour and on the local climatic conditions, the shade promoted triggers different responses by the trees. Grey and black anti-hail nets were applied in an apple orchard (cv. 'Golden Delicious') located in Northeast Portugal. Under the nets a lower concentration of glomalin related-soil proteins was observed, along with an improvement on trees water status, stomatal conductance, net photosynthetic rate, total chlorophylls, N, Mg, Fe and Cu concentrations, as well as an increase in mean fruit weight. The major difference between nets was on the photosynthetic efficiency, being higher on black net in sunny days, while grey net performed better under cloudy conditions. The use of netting systems proved to be effective in improving "Golden Delicious" apple trees performance under a Mediterranean climate, mainly when the radiation reaching the plants surpass the tree saturation point for photosynthesis. Therefore, these findings anticipate solutions for current and forecasted negative effects of climate change.