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One in eight women will be diagnosed with breast cancer in their lifetime and approximately 25% of those cases will be HER2-positive. Current methods for diagnosing HER2-positive breast cancer involve using IHC and FISH from suspected cancer biopsies to quantify HER2 expression. HER2 PET imaging could potentially increase accuracy and improve the diagnosis of lesions that are not available for biopsies. Using two previously discovered HER2-targeting peptides, we modified each peptide with the chelator DOTA and a PEG2 linker resulting in DOTA-PEG2-GSGKCCYSL (P5) and DOTA-PEG2-DTFPYLGWWNPNEYRY (P6). Each peptide was labeled with 68Ga and was evaluated for HER2 binding using in vitro cell studies and in vivo tumor xenograft models. Both [68Ga]P5 and [68Ga]P6 showed significant binding to HER2-positive BT474 cells versus HER2-negative MDA-MB-231 cells ([68Ga]P5; 0.68 ± 0.20 versus 0.47 ± 0.05 p < 0.05 and [68Ga]P6; 0.55 ± 0.21 versus 0.34 ± 0.12 p < 0.01). [68Ga]P5 showed a higher percent injected dose per gram (%ID/g) binding to HER2-positive tumors two hours post-injection compared to HER2-negative tumors (0.24 ± 0.04 versus 0.12 ± 0.06; p < 0.05), while the [68Ga]P6 peptide showed significant binding (0.98 ± 0.22 versus 0.51 ± 0.08; p < 0.05) one hour post-injection. These results lay the groundwork for the use of peptides to image HER2-positive breast cancer.

Background: Dengue is an important public health problem in Argentina, as in many other countries. We reviewed and updated information on the dengue disease burden in Argentina over a 10-year period. Methods: We conducted a retrospective descriptive study from 2010 to 2020 based on data from the National Health Surveillance System. The main outcomes included dengue cases, incidence rates, deaths, and serotype distribution by season, age group, and region. Results: A total of 109,998 confirmed cases of dengue were reported. Seasonality stands out, prevailing during summer and autumn. Two main outbreaks (seasons 2015/16 and 2019/20), with increasing magnitude, were observed. The 2019/20 season showed the highest number of cases (58,731) and incidence rate (135/100,000). The Northeast region had the highest number of cases and incidence rate. In 2020, for the first time, autochthonous cases were registered in the Cuyo region. The only region with no autochthonous cases was the South. Adolescents and young adults showed the highest incidence rate. The case fatality rate for the period was 0.05%. Four serotypes circulated, but the predominant one was DEN-1 (78%). Conclusions: Dengue has been expanding temporally and spatially. Although the DEN-1 serotype widely predominated, the increasing circulation of other serotypes raises concerns regarding re-exposure and the severity of future cases. Understanding epidemiological trends is key to defining public prevention and control policies.

Since the last century, it has been shown that dedifferentiated cells of Camellia sinensis can produce catechins and other secondary metabolites under in vitro conditions, with potential applications in the cosmetic, pharmaceutical and food industries. In this work, cell suspension cultures of a C. sinensis cell line (LSC-5Y) were established in a liquid medium in order to optimize the biomass productivity, catechin monomer (GC, EGC, C, EC, CG, and ECG) and alkaloid (TB and CAF) productivity. The following factors were evaluated: concentration of growth regulators (BA and IBA), inoculum size, age of the cell line, light exposure, and effect of biotic elicitors (MeJA and extracts of Ciborinia camelliae ). GC, EGC, and ECG increased approximately 1.80-fold when the auxin IBA concentration was increased from 0.1 to 2.0 mg/L. In addition, better productivity of EGC, C, EC, and CAF was achieved by using inoculum densities between 50 and 100 g/L. Although lower inoculum densities (25 g/L) showed a higher growth rate (0.20 d -1 ), the use of inoculum densities higher than 25 g/L favors a 2-4-fold increase in total catechin (TC) productivity, with maximum productivity being reached after 21 days of culture. However, the cell line showed instability in TC productivity: in the short term (in three successive subcultures), the coefficient of variation was 32.80%, and catechin production capacity was 2.5 years with maximum productivity at 0.5 years. Finally, it was observed that ethanol, used as an elicitor solvent, has a strong elicitor effect capable of increasing the accumulation of catechins up to 5.24 times compared to the treatment without an elicitor.

The present work was conducted to evaluate the volatile profile of Ecuadorian Forastero, CCN-51, ETT103 and LR14 cocoa beans during traditional fermentation in laurel wood boxes followed by a sun-drying process. Fifty-six volatiles were identified with HS-SPME-GC-MS. Aldehydes, alcohols and ketones were the compounds that mainly characterized the fresh cocoa. The main compounds formed during the anaerobic fermentation step were esters and acids, while in the aerobic fermentation step, an increase in ester-, aldehyde- and acid-type compounds was observed. Finally, after the drying step, a notable increase in the acid (i.e., acetic acid) content was the predominant trend. According to the genotypes, ETT103 presented high contents of terpenes, alcohols, aldehydes and ketones and low contents of unfavorable acid compounds. The CCN-51 and LR14 (Trinitarian) varieties stood out for their highest amounts in acids (i.e., acetic acid) at the end of primary processing. Finally, the Forastero cocoa beans were highlighted for their low acid and high trimethylpyrazine contents. According to the chemometric and Venn diagram analyses, ETT-103 was an interestingly high-aromatic-quality variety for cocoa gourmet preparations. The results also showed the need for good control of the processing steps (using prefermentative treatments, starter cultures, etc.) on Ecuadorian genotypes of Trinitarian origin.

The banana is a tropical fruit characterized by its composition of healthy and nutritional compounds. This fruit is part of traditional Ecuadorian gastronomy, being consumed in a wide variety of ways. In this context, unripe Red Dacca banana samples and those submitted to different traditional Ecuadorian heating treatments (boiling, roasting, and baking) were evaluated to profile their phenolic content by ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) and the antioxidant activity by ORAC, ABTS, and DPPH assays. A total of sixty-eight phenolic compounds were identified or tentatively identified in raw banana and treated samples, highlighting the content in flavonoids (flavan-3-ols with 88.33% and flavonols with 3.24%) followed by the hydroxybenzoic acid family (5.44%) in raw banana samples. The total phenolic compound content significantly decreased for all the elaborations evaluated, specifically from 442.12 mg/100 g DW in fresh bananas to 338.60 mg/100 g DW in boiled (23.41%), 243.63 mg/100 g DW in roasted (44.90%), and 109.85 mg/100 g DW in baked samples (75.15%). Flavan-3-ols and flavonols were the phenolic groups most affected by the heating treatments, while flavanones and hydroxybenzoic acids showed higher stability against the heating treatments, especially the boiled and roasted samples. In general, the decrease in phenolic compounds corresponded with a decline in antioxidant activity, evaluated by different methods, especially in baked samples. The results obtained from PCA studies confirmed that the impact of heating on the composition of some phenolic compounds was different depending on the technique used. In general, the heating processes applied to the banana samples induced phytochemical modifications. Even so, they remain an important source of bioactive compounds for consumers.

Cocoa ( Theobroma cacao L.) is one of the most widely consumed edible seeds in the world affected by on-farm processing. This study investigated the effect of different drying techniques, namely oven drying (OD), sun drying (SD), and a modification of sun drying using black plastic sheeting (SBPD), on the volatile profile of fine-flavor and bulk cocoa varieties analyzed by HS-SPME-GC-MS. A total of sixty-four volatile compounds were identified in fresh and dried cocoa. As expected, the volatile profile was clearly modified after the drying step, showing strong differences among cocoa varieties, this factor and its interaction with the drying technique having greater influence according to the ANOVA simultaneous component analysis. A principal component analysis revealed a close relationship between the volatile content of bulk cocoa samples dried by the OD and SD techniques, whereas slight volatile modifications were perceived among fine-flavor samples dried using the three different techniques under study. Overall, the results provide the basis for the potential application of the simplest inexpensive SBPD technique in order to accelerate the drying process of sun drying and produce cocoa with similar (fine-flavor cocoa) or improved (bulk cocoa) aromatic quality to that formed using the traditional SD or the small-scale OD.

In this study, in vitro cultures and micropropagated plants of two Mediterranean aromatic plants, Lavandula viridis L'Hér and Thymus lotocephalus López and Morales, were exposed to different temperatures (15, 20, 25, and 30 °C). The effect of temperature on the levels of hydrogen peroxide (H 2 O 2 ), lipid peroxidation, and osmoprotectants (proline, soluble sugars, and soluble proteins), as well as on the phenolic profile by HPLC-HRMS and intermediates of the secondary metabolism (phenylalanine ammonia lyase (PAL) activity and shikimic acid content), was investigated. Moreover, the antioxidant activity of the plant extracts was also analyzed. Overall, considering the lipid peroxidation and H 2 O 2 content, the extreme temperatures (15 and 30 °C) caused the greatest damage to both species, but the osmoprotectant response was different depending on the species and plant material. In both species, phenolic compounds and related antioxidant activity increased with the rise in temperature in the micropropagated plants, while the opposite occurred in in vitro cultures. L. viridis cultures showed the highest biosynthesis of rosmarinic acid (92.6 g/kg DW ) at 15 °C and seem to be a good alternative to produce this valuable compound. We conclude that contrasting temperatures greatly influence both species' primary and secondary metabolism, but the response is different depending on the plant micropropagation stage.

One in eight women will be diagnosed with breast cancer in their lifetime and approximately 25% of those cases will be HER2-positive. Current methods for diagnosing HER2-positive breast cancer involve using IHC and FISH from suspected cancer biopsies to quantify HER2 expression. HER2 PET imaging could potentially increase accuracy and improve the diagnosis of lesions that are not available for biopsies. Using two previously discovered HER2-targeting peptides, we modified each peptide with the chelator DOTA and a PEG2 linker resulting in DOTA-PEG2-GSGKCCYSL (P5) and DOTA-PEG2-DTFPYLGWWNPNEYRY (P6). Each peptide was labeled with 68Ga and was evaluated for HER2 binding using in vitro cell studies and in vivo tumor xenograft models. Both [68Ga]P5 and [68Ga]P6 showed significant binding to HER2-positive BT474 cells versus HER2-negative MDA-MB-231 cells ([68Ga]P5; 0.68 ± 0.20 versus 0.47 ± 0.05 p < 0.05 and [68Ga]P6; 0.55 ± 0.21 versus 0.34 ± 0.12 p < 0.01). [68Ga]P5 showed a higher percent injected dose per gram (%ID/g) binding to HER2-positive tumors two hours post-injection compared to HER2-negative tumors (0.24 ± 0.04 versus 0.12 ± 0.06; p < 0.05), while the [68Ga]P6 peptide showed significant binding (0.98 ± 0.22 versus 0.51 ± 0.08; p < 0.05) one hour post-injection. These results lay the groundwork for the use of peptides to image HER2-positive breast cancer.

The impact of drought stress induced by polyethylene glycol (PEG) on morphological, physiological, (bio)chemical, and biological characteristics of Thymus lotocephalus López and Morales shoot cultures have been investigated, as well as the potential of iron oxide nanoparticles, salicylic acid, and methyl jasmonate (MeJA) as alleviating drought stress agents. Results showed that PEG caused oxidative stress in a dose-dependent manner, raising H 2 O 2 levels and reducing shoots' growth, photosynthetic pigment contents, and phenolic compounds production, especially phenolic acids, including the major compound rosmarinic acid. Moreover, Fourier Transform Infrared Spectra analysis revealed that PEG treatment caused changes in shoots' composition, enhancing terpenoids biosynthesis. PEG also decreased the biological activities (antioxidant, anti-tyrosinase, and photoprotective) of the eco-friendly extracts obtained with a Natural Deep Eutectic Solvent. MeJA was the most efficient agent in protecting cells from oxidative damage caused by drought, by improving the biosynthesis of phenolics, like methyl 6-O-galloyl-β-D-glucopyranoside and salvianolic acids, as well as improving the extracts' antioxidant activity. Altogether, the obtained results demonstrated a negative impact of PEG on T. lotocephalus shoots and an effective role of MeJA as a mitigating agent of drought stress. Additionally, extracts showed a good potential to be used in the cosmetics industry as skincare products.

Camellia genus (Theaceae) is comprised of world famous ornamental flowering plants. C. japonica L. and C. sasanqua Thunb are the most cultivated species due to their good adaptation. The commercial interest in this plant linked to its seed oil increased in the last few years due to its health attributes, which significantly depend on different aspects such as species and environmental conditions. Therefore, it is essential to develop fast and reliable methods to distinguish between different varieties and ensure the quality of Camellia seed oils. The present work explores the study of Camellia seed oils by species and location. Two standardized gas chromatography methods were applied and compared with that of data obtained from proton nuclear magnetic resonance spectroscopy ( 1 H-NMR) for fatty acids profiling. The principal component analysis indicated that the proposed 1 H-NMR methodology can be quickly and reliably applied to separate specific Camellia species, which could be extended to other species in future works.

The present study aimed at evaluating the effectiveness of different natural deep eutectic solvents (NADES) on the extraction of phenolic compounds from Lavandula pedunculata subsp. lusitanica (Chaytor) Franco, on the antioxidant activity, and acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and tyrosinase (Tyr) inhibitory capacities. Ten different NADES were used in this research and compared with conventional solvents. Ultrasound-assisted extraction (UAE) for 60 min proved to be the best extraction condition, and proline:lactic acid (1:1) and choline chloride:urea (1:2) extracts showed the highest total phenolic contents (56.00 ± 0.77 mg GAE /g dw ) and antioxidant activity [64.35 ± 1.74 mg TE /g dw and 72.13 ± 0.97 mg TE /g dw in 2.2-diphenyl-1-picrylhydrazyl (DPPH) and 2.2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) methods, respectively]. These extracts also exhibited enzymes inhibitory capacity particularly against Tyr and AChE. Even so, organic acid-based NADES showed to be the best extractants producing extracts with considerable ability to inhibit enzymes. Twenty-four phenolic compounds were identified by HPLC-HRMS, being rosmarinic acid, ferulic acid and salvianolic acid B the major compounds. The results confirmed that the combination of UAE and NADES provide an excellent alternative to organic solvents for sustainable and green extraction, and have huge potential for use in industrial applications involving the extraction of bioactive compounds from plants.

Carob liqueur is a traditional Mediterranean alcoholic beverage obtained via a wide range of production techniques contributing to the different organoleptic attributes of the final product. The aim of this research was to evaluate the stability of the chemical composition and biological capacities (antioxidant and enzyme inhibition) under in vitro simulated gastrointestinal digestion of liqueurs prepared by flavouring the fig spirit with carob pulp by maceration, distillation, percolation, or aqueous and hydro-alcoholic infusions. For this purpose, the phenolic and furanic compositions, the total phenolic (TPC) and flavonoid (TFC) contents, antioxidant capacity (AC), and enzyme inhibitory potential against acethylcholinesterase, tyrosinase, α-glucosidase and α-amylase enzymes were evaluated. The content of gallic acid decreased after gastrointestinal digestion, while TPC, TFC, and AC significantly increased after each digestion phase. Overall, no significantly different enzyme inhibitions ( p < 0.05) were observed among digested liqueurs, with moderate inhibition against acethylcholinesterase and tyrosinase (enzymes related with neurodegenerative diseases), and potent and low inhibitory capacities for α-glucosidase and α-amylase, respectively (ideal conditions employed in antidiabetic therapy). The study indicates that hydro-alcoholic infusion and maceration were the most appropriate methods to obtain liqueurs with higher values of the aforementioned parameters and safe levels of toxic furanics.