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Mountain areas are sensitive to changes in precipitation and temperature, which significantly impact traditional pastoralist communities, their economy, and their lifestyle. Alarming climate change scenarios justify the investigation of the ecological and socioeconomic vulnerabilities that characterize Portugal's mountain regions. This work explores how the traditional production systems of small ruminants—sheep and goats—could adapt in the Montesinho mountain range as it changes over the next 2 decades. Land use–land cover maps from 1995 and 2018 show how the pastoral landscape has changed and indicate trends for a future scenario. Documented landscape grazing patterns are used to determine sheep and goat landscape preferences under different climatic conditions. Finally, we identify the near-future constraints on traditional sheep and goat systems, contrasting landscape changes with sheep and goat preferences. Over coming decades, the balance between rangelands and cultivated lands will persist in the Montesinho mountain landscape, despite some trade-offs between both. Woodlands could emerge from scrublands colonizing rangelands, and permanent crops could significantly replace arable lands in agricultural areas. Therefore, it is likely that the agricultural areas preferred for sheep, and rangelands preferred for goats, may not be affected by the forecast landscape changes, but rather be favored by the expansion of permanent crops. However, pasture areas must expand, as they are key to pastoral landscape function in a warming climate scenario. Landscape decision makers and managers should implement a landscape-monitoring system to inform policies and strategies aimed at protecting and safeguarding mountain pastoralism and its vital ecosystem services.

Poor efficiency of chemotherapeutics in the eradication of Cancer Stem Cells (CSCs) has been driving the search for more active and specific compounds. In this work, we show how cell density-dependent stage culture profiles can be used in drug development workflows to achieve more robust drug activity (IC50 and EC50) results. Using flow cytometry and light microscopy, we characterized the cytological stage profiles of the HL-60-, A-549-, and HEK-293-derived sublines with a focus on their primitive cell content. We then used a range of cytotoxic substances—C-123, bortezomib, idarubicin, C-1305, doxorubicin, DMSO, and ethanol—to highlight typical density-related issues accompanying drug activity determination. We also showed that drug EC50 and selectivity indices normalized to primitive cell content are more accurate activity measurements. We tested our approach by calculating the corrected selectivity index of a novel chemotherapeutic candidate, C-123. Overall, our study highlights the usefulness of accounting for primitive cell fractions in the assessment of drug efficiency.

The aim of this study was to determine, first, the chemical composition of Aloysia polystachya (Griseb) Moldenke essential oil, from leaves harvested in central Chile; and second, its antioxidant and cytotoxic activity. Eight compounds were identified via gas chromatography–mass spectrometry (GC–MS) analyses, with the most representative being R-carvone (91.03%), R-limonene (4.10%), and dihydrocarvone (1.07%). For Aloysia polystachya essential oil, antioxidant assays (2,2-diphenyl-1-picrylhydrazyl (DPPH), H2O2, ferric reducing antioxidant power (FRAP), and total reactive antioxidant potential (TRAP)) showed good antioxidant activity compared to commercial antioxidant controls; and anti-proliferative assays against three human cancer cell lines (colon, HT-29; prostate, PC-3; and breast, MCF-7) determined an IC50 of 5.85, 6.74, and 9.53 µg/mL, and selectivity indices of 4.75, 4.12, and 2.92 for HT-29, PC-3, and MCF-7, respectively. We also report on assays with CCD 841 CoN (colon epithelial). Overall, results from this study may represent, in the near future, developments for natural-based cancer treatments.

ObjectiveThe aim of this study was to evaluate the rate of adrenal venous sampling (AVS) performance in patients with primary aldosteronism (PA), the main reasons for its non-performance, and the success and complications rate of this procedure in Spain. Moreover, the concordance between CT/MRI and AVS for PA subtyping was evaluated.MethodsA retrospective multicenter study of PA patient follow-up in 20 Spanish tertiary hospitals between 2018–2021 was performed (SPAIN-ALDO Register).ResultsOf the 440 patients with PA included in the study, 153 underwent AVS (34.8%). The main reasons for not performing AVS were: patient rejection to the procedure, low catheterization rate in the center and unilateral disease based on CT/MRI. The overall success rate was 44.4% (the left adrenal vein was properly canulated in 77.8% and the right adrenal vein in 48.4%). Only 3 patients experienced minor complications. In the 45 patients with unilateral disease according to AVS, CT/MRI indicated bilateral disease or normal adrenal glands in 17. In the 23 patients with bilateral disease, CT/MRI indicated unilateral disease in 14. However, no significant differences were observed in biochemical response (P = 0.051) and hypertension resolution (P = 0.150) between patients who underwent surgery based on CT/MRI results and those who underwent surgery based on AVS results.ConclusionIn our setting, AVS is still an underused technique in patients with PA. The low experience and success rate in AVS partially justify these results. More training for providers and patients needs to be done to include appropriate well performed AVS in the diagnosis algorithm of PA.

(1) Background: Essential oils (EOs) have emerged as promising antibacterial agents due to their broad-spectrum activity and low risk of resistance development. Therefore, this review aimed to assess the effectiveness of EOs against Gram-positive ESKAPE pathogens, and to evaluate their safety and toxicity in mammalian cells. (2) Methods: A comprehensive search was conducted in PubMed, Scopus, and Web of Science. (3) Results: Heracleum pyrenaicum exhibited the most potent effect, with a MIC of 0.02–0.04 µg/mL and a selectivity index ranging from 251.3 to 2006.5, indicating high selective toxicity toward bacterial cells over mammalian cells. In contrast, certain species such as Cannabis sp. and Citrus sp. had selectivity indices of <1, indicating toxicity to mammalian cells. Ocimum basilicum showed good efficacy against methicillin-resistant S. aureus (MRSA), with a selectivity index of 23.4–34.9, while Satureja nabateorum demonstrated potent activity against E. faecium, with a selectivity index of 65.6–87.2. (4) Conclusions: EOs from Heracleum, Eucalyptus, Cinnamomum, Mentha, Thymus, and Syzygium aromaticum had good efficacy and high safety margins and show a potential for development for treating Gram-positive ESKAPE pathogen infections. However, EOs with a narrow safety margin (selectivity index < 10) raise concerns and warrant further in vivo and clinical trials to better understand their therapeutic windows and potential adverse effects.

Backgrounds: Pinostrobin has the potential activity as an anti-cancer. However, its activity is still lower than the anticancer drugs on the market. To increase its activity, pinostrobin derivatives have been synthesized, namely pinostrobin propionate and pinostrobin butyrate, which are predicted to have better activity and lower toxicity than pinostrobin after being tested by in silico approach. So the compound deserves to be tested for its anticancer activity and selectivity on normal cells. Objective: This study aims to determine the anticancer activity of pinostrobin propionate and pinostrobin butyrate against the T47D breast cancer cell line and its selectivity against the Vero cell line. Methods: The cytotoxicity test which is anticancer activity test and its selectivity on normal cell were carried out using the MTT(3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. The cells used were breast cancer cell line T47D and normal Vero cells. The test results were analyzed using a microplate reader with a wavelength of 570 nm. Results: From the analysis of anticancer activity on T47D cells, the IC50 values of pinostrobin, pinostrobin propionate, and pinostrobin butyrate were 2.93, 0.57, and 0.40 mM, respectively. While the results of the cytotoxicity test on Vero cells obtained the CC50 value of pinostrobin, pinostrobin propionate, pinostrobin butyrate was 1.27, 0.94, and 0.89 mM, respectively. So the SI value of pinostrobin (SI=0.4) is smaller than its derivatives (SI=1.7 and 2.2). Meanwhile, pinostrobin butyrate is more selective than pinostrobin propionate. Conclusions: It can be concluded that pinostrobin propionate and pinostrobin butyrate compounds have greater activity and selectivity than pinostrobin so these compounds are promising to be further developed as anticancer candidates.

The purposeful introduction of the land snail Euglandina rosea, which feeds exclusively on snails and slugs, has been implicated as a major factor in the decline of diverse Pacific island land snail faunas. We report on the distribution, movement patterns, and microhabitat preferences of E. rosea in a gulch in the Waianae Mountains, Oahu, Hawaii, because such data will help focus management actions at a local scale to protect native snail populations in areas where E. rosea is established. The Waianae Mountains harbor many endangered or threatened snails, most currently found in isolated habitat patches near the ridges. Conversely, most living individuals (28/29) and shells (46/56) of E. rosea were collected within the gulch, which supported higher densities of other native and non‐native snails, and was cooler and more moist than the ridges. Thirteen individuals of E. rosea were tracked (eight directly using a bobbin and thread method, and five indirectly by mark–recapture); most (10/13) moved on average <2.5 m per week (range 0.1–25.21 m), and all stayed within the gulch. Members of E. rosea preferred leaf litter over open, fern/shrub, or wood microhabitats. There were large differences in the population density of E. rosea over small spatial scales, indicating that there may be places where native snail populations could persist even in areas where populations of E. rosea are established. Identifying areas with differing population densities of E. rosea is critical for not only understanding why some native snail species may be more vulnerable to extinction, but also to locate areas where predation pressure is low and conservation efforts will be most likely to succeed.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the second largest contributor to cancer mortality. Sorafenib (SOR) is a drug approved by the Food and Drug Administration (FDA) to treat liver cancer, but it has harsh side effects on normal cells, is expensive, and is associated with chemoresistance through frequent use. This work aims to test the hypothesis that loading sorafenib onto a metal-organic framework (MOF) as a nanocarrier can help increase the potency and selectivity of sorafenib on hepatocellular carcinoma (HCC) and explore its potential application in colorectal cancer treatment. MOFs were prepared and chemically characterized using XRD, FTIR, and BET. The crystallite size was calculated using the Scherrer equation, and comprehensive FTIR peak assignments were performed to elucidate drug-MOF interactions. Sorafenib was loaded onto the MOF, entrapment efficiency (EE) as well as loading capacity (LC) were calculated using the formulas: EE% = (sorafenib content loaded in MIL-53(Fe)) / (initial sorafenib content) × 100% and LC% = (sorafenib content loaded in MIL-53(Fe)) / (sorafenib loaded + weight of MIL-53(Fe)) × 100%, and in vitro release was evaluated under sink conditions in phosphate-buffered saline (PBS, pH 7.4). The cytotoxic effect of sorafenib on normal HFb-4, HepG2, and HCT-116 cells was measured before and after loading onto MOF, and the selectivity index (SI) was calculated using the formula: SI = IC 50 (normal cells) / IC 50 (cancer cells). Apoptosis and cell cycle analysis were also performed using flow cytometry. The present study showed entrapment efficiency (EE) = 88.97% and loading capacity (LC) = 23.5% of sorafenib. The high variability in LC indicates batch-to-batch reproducibility challenges that require optimization. Spontaneous release of the loaded drug was encountered within 48 h. XRD analysis showed crystallite sizes calculated using the Scherrer equation, confirming successful drug encapsulation with reduced crystallinity of sorafenib within the MOF structure. Before loading, the MTT test showed IC 50 for sorafenib = 5.88, 12.5, 29.4 µg/ml on HFb-4, HepG2, and HCT-116 cells, respectively. After loading, IC 50 values of 3.3, 5.5, and 7.9 µg/ml were found considering the loading capacity. The selectivity index (SI) values showed modest improvements: 0.46 to 0.6 for HepG2 and 0.2 to 0.42 for HCT-116. While these improvements are statistically significant, the SI values remain below the ideal threshold of > 2, indicating that further optimization is needed to achieve clinically relevant selectivity. There was a direct correlation between the cytotoxic effect and the degree of apoptosis in the HepG2 cell line. The present study has also proved cell cycle arrest at the G0/G1 phase after treatment with sorafenib loaded onto the MOF (SOR-MIL-53). We conclude from the current study that MOF as a carrier is considered a promising nanocarrier for enhancing drug potency as an anti-cancer agent, though selectivity improvements remain modest. Loading Sorafenib on MOF showed enhanced potency on HepG2 cell lines and demonstrated potential for colorectal cancer applications, despite sorafenib not being FDA-approved for this indication.

Background Cancer is a major global health challenge, driving the need for new therapeutic agents. This study explored the anticancer potential of microorganisms isolated from healthy bee workers collected from 35 sites in three Egyptian governorates to identify novel bioactive metabolites. Results A total of 113 microbial isolates (35 fungal and 78 bacterial) were obtained and screened. Thirty-two selected isolates were fermented, and their cytotoxicity against MCF-7 breast cancer cells was assessed using the MTT assay. Eight isolates showed strong anticancer activity, reducing cell viability below 30%. Among them, isolate Tm2 demonstrated the highest selectivity and potency across multiple cancer cell lines (Caco-2, MCF-7, HepG-2, A549), with IC50 values between 30.63 and 113.39 µg/ml, and minimal toxicity toward normal cells (IC50 > 976 µg/ml; selectivity index = 18.21). Morphological and molecular analyses identified Tm2 as Aspergillus oryzae . Optimization of fermentation parameters via Plackett-Burman and Box-Behnken designs maximized extract yield to 1.86 g/100 ml under specific conditions (yeast extract 1.5 g/L, pH 7.6, 25 °C). Chemical profiling using GC-MS and UPLC-MS/MS detected 65 bioactive compounds, mainly fatty acids such as oleic, hexadecanoic, and linoleic acids. Live-dead staining showed dose-dependent cytotoxic effects, while flow cytometry revealed induction of apoptosis through multiple pathways in cancer cells treated with the extract. Conclusions Aspergillus oryzae isolated from bee microbiota exhibits potent and selective anticancer activity mediated by a complex mixture of bioactive fatty acids. These results highlight its potential as a novel source for developing effective anticancer therapies with low toxicity to normal cells.

Illegal wildlife trade, which mostly focuses on high-demand species, constitutes a major threat to biodiversity. However, whether poaching is an opportunistic crime within high-demand taxa such as parrots (i.e., harvesting proportional to species availability in the wild), or is selectively focused on particular, more desirable species, is still under debate. Answering this question has important conservation implications because selective poaching can lead to the extinction of some species through overharvesting. However, the challenges of estimating species abundances in the wild have hampered studies on this subject. We conducted a large-scale survey in Colombia to simultaneously estimate the relative abundance of wild parrots through roadside surveys (recording 10,811 individuals from 25 species across 2221 km surveyed) and as household, illegally trapped pets in 282 sampled villages (1179 individuals from 21 species). We used for the first time a selectivity index to test selection on poaching. Results demonstrated that poaching is not opportunistic, but positively selects species based on their attractiveness, defined as a function of species size, coloration, and ability to talk, which is also reflected in their local prices. Our methodological approach, which shows how selection increases the conservation impacts of poaching for parrots, can be applied to other taxa also impacted by harvesting for trade or other purposes.