Effect of Salt Addition and Fermentation Time on Phenolics,Microbial Dynamics,Volatile Organic Compounds,and Sensory Properties of the PDO Table Olives of Gaeta (Italy)

‘Oliva di Gaeta’ is almost certainly the most important and well-known PDO denomination for table olives in Italy. Their production is based on a specific two-stage trade preparation called the ‘Itrana’ method. In this work, we investigated how variations in the duration of the initial water fermentation (i.e., 15 and 30 days) and the salt concentration (i.e., 6% and 8% NaCl) influence the chemical features, microbial dynamics, polyphenols, volatile organic compounds, and sensory features of ‘Oliva di Gaeta’. The time of the addition of salt did not affect the final concentration in the brine, but a longer initial water fermentation (before salt addition) led to lower pH values. The bacterial count constantly increased until the salt addition (i.e., either 15 or 30 days), while the yeast population peaked on day 30. Generally, the two different salt concentrations did not affect the count of microorganisms at the end of fermentation, with the only exception being a higher lactic acid bacteria count for the treatment with 6% salt added at 30 days. At commercial maturity, the crucial bitter tastant oleuropein was not completely removed from the drupes, and differences in salt concentration and the length of the first-stage water fermentation did not influence its content at the end of olive curing. Richer volatile profiles of olives were detected with higher-salt treatments, while the combination of low salt and early saline treatment provided a more distinct profile. Longer initial water fermentation caused a small increase in some phenolic compounds (e.g., iso-verbascoside, verbascoside, and hydroxytyrosol-glucoside). A panel test indicated that salt application at 30 days resulted in a more “Sour” and “Bitter” taste, irrespective of the salt concentration. The low salt concentration coupled with the late saline treatment resulted in more “Fruity” notes, probably due to the higher production of esters by lactobacilli. The slightly bitter perception of the olives was consistent with the partial removal of oleuropein. Our work revealed the characteristics of the ‘Itrana’ method and that the variation in salt concentration and its time of application changes parameters ranging from the microbial dynamics to the sensory profile. Specifically, our data indicate that 6% NaCl coupled with a longer initial water fermentation is the most different condition: it is less effective in blocking microbial growth but, at the same time, is more potent in altering the nutritional (e.g., polyphenols) and sensorial qualities (e.g., bitterness and fruitiness) of ‘Oliva di Gaeta’.     

Investigation into the Use of Encorafenib to Develop Potential PROTACs Directed against BRAFV600E Protein

BRAF is a serine/threonine kinase frequently mutated in human cancers. BRAF^V600E mutated protein is targeted through the use of kinase inhibitors which are approved for the treatment of melanoma; however, their long-term efficacy is hampered by resistance mechanisms. The PROTAC-induced degradation of BRAF^V600E has been proposed as an alternative strategy to avoid the onset of resistance. In this study, we designed a series of compounds where the BRAF kinase inhibitor encorafenib was conjugated to pomalidomide through different linkers. The synthesized compounds maintained their ability to inhibit the kinase activity of mutated BRAF with IC₅₀ values in the 40–88 nM range. Selected compounds inhibited BRAF^V600E signaling and cellular proliferation of A375 and Colo205 tumor cell lines. Compounds 10 and 11, the most active of the series, were not able to induce degradation of mutated BRAF. Docking and molecular dynamic studies, conducted in comparison with the efficient BRAF degrader P5B, suggest that a different orientation of the linker bearing the pomalidomide substructure, together with a decreased mobility of the solvent-exposed part of the conjugates, could explain this behavior.     

Psidium guajava L. An Incalculable but Underexplored Food Crop: Its Phytochemistry,Ethnopharmacology, and Industrial Applications

Psidium guajava L. (guava) is a small tree known for its fruit flavor that is cultivated almost around the globe in tropical areas. Its fruit is amazingly rich in antioxidants, vitamin C, potassium, and dietary fiber. In different parts of the world, this plant holds a special place with respect to fruit and nutritional items. Pharmacological research has shown that this plant has more potential than just a fruit source; it also has beneficial effects against a variety of chronic diseases due to its rich nutritional and phytochemical profile. The primary goal of this document is to provide an updated overview of Psidium guajava L. and its bioactive secondary metabolites, as well as their availability for further study, with a focus on the health benefits and potential industrial applications. There have been several studies conducted on Psidium guajava L. in relation to its use in the pharmaceutical industry. However, its clinical efficacy and applications are still debatable. Therefore, in this review a detailed study with respect to phytochemistry of the plant through modern instruments such as GC and LC-MS has been discussed. The biological activities of secondary metabolites isolated from this plant have been extensively discussed. In order to perform long-term clinical trials to learn more about their effectiveness as drugs and applications for various health benefits, a structure activity relationship has been established. Based on the literature, it is concluded that this plant has a wide variety of biopharmaceutical applications. As a whole, this article calls for long-term clinical trials to obtain a greater understanding of how it can be used to treat different diseases.     

7-Hydroxycoumarin Induces Vasorelaxation in Animals with Essential Hypertension: Focus on Potassium Channels and Intracellular Ca2+ Mobilization

Cardiovascular diseases (CVD) are the deadliest noncommunicable disease worldwide. Hypertension is the most prevalent risk factor for the development of CVD. Although there is a wide range of antihypertensive drugs, there still remains a lack of blood pressure control options for hypertensive patients. Additionally, natural products remain crucial to the design of new drugs. The natural product 7-hydroxycoumarin (7-HC) exhibits pharmacological properties linked to antihypertensive mechanisms of action. This study aimed to evaluate the vascular effects of 7-HC in an experimental model of essential hypertension. The isometric tension measurements assessed the relaxant effect induced by 7-HC (0.001 μM–300 μM) in superior mesenteric arteries isolated from hypertensive rats (SHR, 200–300 g). Our results suggest that the relaxant effect induced by 7-HC rely on K⁺-channels (K_ATP, BK_Ca, and, to a lesser extent, K_v) activation and also on Ca²⁺ influx from sarcolemma and sarcoplasmic reticulum mobilization (inositol 1,4,5-triphosphate (IP3) and ryanodine receptors). Moreover, 7-HC diminishes the mesenteric artery’s responsiveness to α1-adrenergic agonist challenge and improves the actions of the muscarinic agonist and NO donor. The present work demonstrated that the relaxant mechanism of 7-HC in SHR involves endothelium-independent vasorelaxant factors. Additionally, 7-HC reduced vasoconstriction of the sympathetic agonist while improving vascular endothelium-dependent and independent relaxation.     

Formation of Quaternary Stereogenic Centers by NHC–Cu‐Catalyzed Asymmetric Conjugate Addition Reactions with Grignard Reagents on Polyconjugated Cyclic Enones

The copper‐catalyzed conjugate addition of various Grignard reagents to polyconjugated enones (dienone and enynone derivatives) is reported. The catalyst system, composed of copper triflate and an NHC ligand, led to the unusual selective formation of the 1,4‐addition products. This reaction allows for the creation of all‐carbon chiral quaternary centers with enantiomeric excesses up to 99 %. The remaining unsaturation on the 1,4 adducts give access to valuable synthetic transformations.     

Behaviour of Bu(CH2—CHCH2)SnCl2 in water and water-cosolvent media: An approach to understanding the chemical degradation of organotins in aquatic environments

The behaviour of allylbutyltin dichloride in water, water–ethanol and water–hexane media, under either homogeneous or heterogeneous conditions, has been studied. 1,3-Diallyl-1,3-dibutyl-1,3-dichlorodistannoxane, butyltin di(hydroxy)chloride and butyltin trichloride arise from the solvolytic, acid–base and degradation processes. The degradation process involving the cleavage of the tin–carbon allyl bond has been interpreted to occur via an intramolecular reaction at the expense of the cation [Bu(CH₂=CHCH₂)Sn(OH)(H₂O)_n]⁺. The mechanistic pathway is ascribable to an internal interaction of the electrophilic cation with a bonded water molecule. This mechanistic proposal may be of some help with understanding of the chemical degradation of diorganotin derivatives in aquatic environments.     

Evidence of nuclear motion in H<Subscript>2</Subscript>-like molecules by means of high harmonic generation

The dynamics of hydrogen-like molecules is investigated beyond the usual fixed nuclei approximation. The nuclear motion introduces in the familiar spectrum of emitted radiation additional regular lines whose separation is essentially given by the vibrational frequency of nuclear motion. A wavelet analysis of the emitted spectrum shows that the intensity of the harmonic lines is modulated with the same period of the nuclear motion; this suggests the possibility of the real-time control of the nuclear dynamics.     

An electroanalytical investigation of the olefin isomerization reaction promoted by electrogenerated cationic nickel(I) complexes

Summary Evidence for the ability of the electrogenerated cationic nickel(I) complex [Ni(PPh₃)₄]⁺ to promote the isomerization of allylbenzene is reported. However, the corresponding triethylphosphitenickel(I) complex displays no catalytic activity, apparently due to the poor leavinggroup character exhibited by the phosphite. The involvement of a -allylnickel hydride in the isomerization reaction is inferred from a comparison of the results obtained with those for the same reaction promoted by nickel hydride.     

Stimulated bremestrahlung in the presence of a high-intensity radiation field

Summary The theoretical treatment is given for the case when the emission or absorption of a weak-fied photon of arbitrary frequency ω₁ during a scattering process takes places in the presence of a strong laser field. The general formulation of the theory which is given in detail corresponds more properly to the case when an electron is scattered by a static potential in the presence of two arbitrary radiation fields. Part of theory is expected to cover also the process of the stimulated bremsstrahlung. A selected set of calculations is performed in the first order in the scattering potential for the case when one of the two fields is weak. The effects of the two fields are always treated exactly. The chosen geometry is the parallel one, in which the two linearly polarized fields are parallel to the initial electron velocity. The presence of a strong assisting field is found to yield several significant modification of the characteristics of emission/absorption of a weak-field photon. In paritcular, i) the final electron energy distribution is drastically altered; ii) angular distributions and total cross-sections of emission and absorption are modified up to become largely similar; iii) when the oscillatory velocityv ₀ is approximately equal to the incoming velocityv _i, the cross-sections experience rapid variations, generally in the sense of the growth; iv) for higher intensities, whenv ₀>v _i the strong field is found instead to dump considerably all the cross-sections, besides making emission and absorption similar. Accordingly, in the high-intensity domain, the question whether or not emissions prevail over absorptions looses part of its importance. In general, calculation shows that the quantities, accounting for the balance between emission and absorption, exhibit strong oscillations above and below zero either as a function of the strong-field intensity or as a function of the weak-field frequency.

---

Riassunto Si propone un trattamento teorico per i processi di emissione e assorbimento di un fotone di campo debole a frequenza arbitraria ω₁ durante un processo di scattering in presenza di un forte campo laser. La formulazione generale della teoria è data in dettaglio relativamente al caso di un elettrone diffuso da un potenziale statico in presenza di due campi di radiazione di intensità arbitraria. La teoria sviluppata, è applicabile anche alla descrizione del processo di bremsstrahlung stimolato. Si presenta un gruppo di risultati ottenuti con una teoria al primo ordine nel potenziale statico, per il caso in cui uno dei due campi è debole. Gli effetti dei due campi sono trattati sempre in modo esatto. I risultati mostrano che la presenza di un forte campo laser è responsabile di numerose importanti modifiche delle caratteristiche dei processi di emissione/assorbimento di un fotone di campo debole. In particolare i) viene alterata drasticamente la distribuzione dell'energia finale degli elettroni; ii) le distribuzioni angolari e le sezioni d'urto totali d'emissione e assorbimento sono modificate fino a divenire largamente simili; iii) quando l'ampiezza della velocità di oscillazionev ₀ è approssimativamente uguale alla velocità di incidenzav _i , le sezioni d'urto subiscono rapide variazioni, generalmente nel senso della crescita; iv) per intensità piú elevate, quandov ₀>v _i , si trova che il campo spettatore riduce sensibilmente le sezioni d'urto, oltre a renderle simili. Di conseguenza, nel dominio delle alte intensità, la questione della prevalenza dell'emissione sopra l'assorbimento perde parte della sua importanza. In generale, il calcolo mostra che le quantità fisiche, che rendono conto del bilancio fra emissione e assorbimento, presentano un andamento oscillatorio, sopra e sotto lo zero, sia come funzioni dell'intensità del campo forte sia come funzioni della frequenza del campo debole.

---

Резюме Теоретически рассматривается случай, когда излучение или поглощение фотона слабого поля произвольной частоты ω₁ в процессе рассеяния происходит в присутствии сильного лазерного поля. Предлагается общая формулировка теории, которая соответствует случаю, когда электрон рассеивается на статическом потенциале в присутствиии двух произволных радиационных полей. Часть теории описывает процесс стимулированного тормозного излучения. Проводятся вычисления в первом порядке по потенциалу рассеяния, когда одно из двух полей является слабым. Влияния двух полей всегда рассматривается точно. Выбранная геометрия соответствует случаю, когда два линейно поляризованных поля являются параллельными первоначальной скорости электрона. Обнаружено, что наличие дополнительнго поля приводит к существенному изменению характеристик излучения (или поглощения) фотона слабого поля. В частности: 1) существенно изменяется конечное энергетическое распределение электрона; 2) изменяются угловые распределения и полные поперечные сечения излучения и поглощения и становатся похожими; 3) когда осцилляторная скоростьv ₀ приближенно равна скорости налетающего электронаv _i поперечные сечения испытывают сильные изменения; 4) для высоких интенсивостей, когдаv ₀>v _i , отмечают значительное уменьшение поперечных сечений. В области высоких интенсивностей важным становится вопрос о том, превалируют ли процессы излучения над процессами поглощения или нет. В общем случае вычисления показывают, что величина, определяющая баланс между излучением и поглощением, обнаруживает сильные осцилляции выше и ниже нуля в зависимости от интенсивности поля или в зависимости от частоты слабого поля.