Energy-based devices and hyaluronic acid filler, polymer filler, and threads: Cadaveric study.

INTRODUCTION: The objective of this experiment was to investigate the thermal effects on hyaluronic acid fillers, PCL fillers, and PDO threads when exposed to controlled heat. This study aims to provide insights into how these materials respond to thermal energy, which is crucial for safe and effective cosmetic procedures involving combined modalities. MATERIALS AND METHODS: Cadaveric tissue was utilized to simulate clinical conditions. Hyaluronic acid fillers were injected at approximately 1 mm and 5 mm thicknesses, with variations in G' value (high and low). PCL fillers were similarly injected in 1 mm and 5 mm thicknesses. PDO threads were also inserted. All materials were injected at a depth of 2 cm. A thermometer was used to measure heat penetration, and a multi-wavelength laser was applied to the tissue. The temperature was maintained at 60°C for 5 min to assess whether heat penetrated more than 3 cm in thickness. Observations were made regarding the heat distribution and any physical changes in the fillers and threads. RESULTS: In thick layers, heat accumulated above the PCL filler without penetrating deeper layers. In thin layers, heat penetration was observed. For the HA fillers, heat energy was not blocked, regardless of the G' value or thickness. For the threads, no significant heat blockage effect was observed. For all materials, no visual changes were detected in any of the materials due to temperature exposure. DISCUSSION: The findings suggest that the thickness and composition of fillers significantly influence heat penetration. Thick PCL fillers act as a thermal barrier, whereas thin PCL fillers allow deeper heat penetration. Hyaluronic acid fillers do not impede heat transfer, regardless of their physical properties. PDO threads do not exhibit any notable thermal resistance. These insights are essential for optimizing the safety and efficacy of combined filler and energy-based device treatments in esthetic medicine.

Nonaqueous Synthesis of Pd/PdO-Functionalized NiFe2O4 Nanoparticles Enabled Enhancing n-Butanol Detection.

The efficient detection of n-butanol, which is in demand for highly sensitive materials, is essential for multiple applications. A nonaqueous method was applied to prepare NiFe2O4 nanoparticles (NPs) using benzyl alcohol as a solvent, which shows a size of 7.9 ± 1.6 nm and a large surface area of 82.23 m2/g. To further improve the sensing performance for n-butanol, Pd/PdO functionalization was sensitized with NiFe2O4 NPs. Gas sensing results demonstrate that the Pd/PdO-NiFe2O4 exhibits an enhanced response of 36.9 to 300 ppm n-butanol and a fast response and recovery time (18.2/17.6 s) at 260 °C. Furthermore, the Pd/PdO-NiFe2O4-based sensor possesses a good linear relationship between responses and the n-butanol concentration from 1 to 1000 ppm, and great selectivity against other volatile organic compounds (VOCs). The excellent sensing enhancement is attributed to the catalytic effects of Pd/PdO, the increase of oxygen vacancies, and the formation of heterojunction between PdO and NiFe2O4. Thus, this study offers an effective route for the synthesis of Pd/PdO-functionalized NiFe2O4 NPs to achieve n-butanol detection with excellent sensing performance.

Explainable artificial intelligence and microbiome data for food geographical origin: the Mozzarella di Bufala Campana PDO Case of Study.

Identifying the origin of a food product holds paramount importance in ensuring food safety, quality, and authenticity. Knowing where a food item comes from provides crucial information about its production methods, handling practices, and potential exposure to contaminants. Machine learning techniques play a pivotal role in this process by enabling the analysis of complex data sets to uncover patterns and associations that can reveal the geographical source of a food item. This study aims to investigate the potential use of explainable artificial intelligence for identifying the food origin. The case of study of Mozzarella di Bufala Campana PDO has been considered by examining the composition of the microbiota in each samples. Three different supervised machine learning algorithms have been compared and the best classifier model is represented by Random Forest with an Area Under the Curve (AUC) value of 0.93 and the top accuracy of 0.87. Machine learning models effectively classify origin, offering innovative ways to authenticate regional products and support local economies. Further research can explore microbiota analysis and extend applicability to diverse food products and contexts for enhanced accuracy and broader impact.

Boosting prairie dog optimizer for optimal planning of multiple wind turbine and photovoltaic distributed generators in distribution networks considering different dynamic load models.

Deploying distributed generators (DGs) supplied by renewable energy resources poses a significant challenge for efficient power grid operation. The proper sizing and placement of DGs, specifically photovoltaics (PVs) and wind turbines (WTs), remain crucial due to the uncertain characteristics of renewable energy. To overcome these challenges, this study explores an enhanced version of a meta-heuristic technique called the prairie dog optimizer (PDO). The modified prairie dogs optimizer (mPDO) incorporates a novel exploration phase inspired by the slime mold algorithm (SMA) food approach. The mPDO algorithm is proposed to analyze the substantial effects of different dynamic load characteristics on the performance of the distribution networks and the designing of the PV-based and WT-based DGs. The optimization problem incorporates various operational constraints to mitigate energy loss in the distribution networks. Further, the study addresses uncertainties related to the random characteristics of PV and WT power outputs by employing appropriate probability distributions. The mPDO algorithm is evaluated using cec2020 benchmark suit test functions and rigorous statistical analysis to mathematically measure its success rate and efficacy while considering different type of optimization problems. The developed mPDO algorithm is applied to incorporate both PV and WT units, individually and simultaneously, into the IEEE 69-bus distribution network. This is achieved considering residential, commercial, industrial, and mixed time-varying voltage-dependent load demands. The efficacy of the modified algorithm is demonstrated using the standard benchmark functions, and a comparative analysis is conducted with the original PDO and other well-known algorithms, utilizing various statistical metrics. The numerical findings emphasize the significant influence of load type and time-varying generation in DG planning. Moreover, the mPDO algorithm beats the alternatives and improves distributed generators' technical advantages across all examined scenarios.

Metagenomic analysis of the bacterial microbiome, resistome and virulome distinguishes Portuguese Serra da Estrela PDO cheeses from similar non-PDO cheeses: An exploratory approach.

This study aimed to evaluate the microbiome, resistome and virulome of two types of Portuguese cheese using high throughput sequencing (HTS). Culture-dependent chromogenic methods were also used for certain groups/microorganisms. Eight samples of raw ewe's milk cheese were obtained from four producers: two producers with cheeses with a PDO (Protected Designation of Origin) label and the other two producers with cheeses without a PDO label. Agar-based culture methods were used to quantify total mesophiles, Enterobacteriaceae, Escherichia coli, Staphylococcus, Enterococcus and lactic acid bacteria. The presence of Listeria monocytogenes and Salmonella was also investigated. The selected isolates were identified by 16S rRNA gene sequencing and evaluated to determine antibiotic resistance and the presence of virulence genes. The eight cheese samples analyzed broadly complied with EC regulations in terms of the microbiological safety criteria. The HTS results demonstrated that Leuconostoc mesenteroides, Lactococcus lactis, Lactobacillus plantarum, Lacticaseibacillus rhamnosus, Enterococcus durans and Lactobacillus coryniformis were the most prevalent bacterial species in cheeses. The composition of the bacterial community varied, not only between PDO and non-PDO cheeses, but also between producers, particularly between the two non-PDO cheeses. Alpha-diversity analyses showed that PDO cheeses had greater bacterial diversity than non-PDO cheeses, demonstrating that the diversity of spontaneously fermented foods is significantly higher in cheeses produced without the addition of food preservatives and dairy ferments. Despite complying with microbiological regulations, both PDO and non-PDO cheeses harbored potential virulence genes as well as antibiotic resistance genes. However, PDO cheeses exhibited fewer of these virulence and antibiotic resistance genes compared to non-PDO cheeses. Therefore, the combination of conventional microbiological methods and the metagenomic approach could contribute to improving the attribution of the PDO label to this type of cheese.

Effects of the Biomimetic Microstructure in Electrospun Fiber Sutures and Mechanical Tension on Tissue Repair.

Electrospun microfibers, designed to emulate the extracellular matrix (ECM), play a crucial role in regulating the cellular microenvironment for tissue repair. Understanding their mechanical influence and inherent biological interactions at the ECM interface, however, remains a complex challenge. This study delves into the role of mechanical cues in tissue repair by fabricating Col/PLCL microfibers with varying chemical compositions and alignments that mimic the structure of the ECM. Furthermore, we optimized these microfibers to create the Col/PLCL@PDO aligned suture, with a specific emphasis on mechanical tension in tissue repair. The result reveals that within fibers of identical chemical composition, fibroblast proliferation is more pronounced in aligned fibers than in unaligned ones. Moreover, cells on aligned fibers exhibit an increased aspect ratio. In vivo experiments demonstrated that as the tension increased to a certain level, cell proliferation augmented, cells assumed more elongated morphologies with distinct protrusions, and there was an elevated secretion of collagen III and tension suture, facilitating soft tissue repair. This research illuminates the structural and mechanical dynamics of electrospun fiber scaffolds; it will provide crucial insights for the advancement of precise and controllable tissue engineering materials.

The impact of nutri-score on consumers' preferences for geographical indications. Evidence from a non-hypothetical experiment.

The EU Farm to Fork strategy (F2F) promotes the compulsory adoption of a nutritional front of pack label to improve the diets of the citizens, supporting healthier food choices. In the public debate, Nutri-Score (NS) is the most favored candidate. Although being widely supported, oppositions on the political and producer levels are raised against the NS, due to the economic impact it could have on specific food sector, and specifically on Geographical Indications (GIs). Recent literature has stressed the need to explore it in more detail. The current study contributes to fill this gap by analyzing consumers' monetary preferences for GI products labelled with different NS levels. An incentivized non-hypothetical experiment was conducted on 188 Italian consumers. Different products representing different levels of NS were used. Specifically, a conventional pasta and the Pasta di Gragnano PGI (NS = A), a conventional flatbread (piadina) and the Piadina Romagnola PGI (NSC), and a conventional hard cheese and the Parmigiano Reggiano PDO (NS = D) were considered in the survey. Results reveal that the NS elicits favorable responses and unfavorable reactions in consumers' preferences, aligning with expectations for A and D scores, respectively. The perceived healthiness of the product significantly affects consumers' WTP, increasing it. Results stress the need to have effective communication strategies within the EU to reach the F2F goals. NS diminishes the premium in prices associated with GIs independently from its level, when considering those consumers who value more the GIs. However, the most well-known GIs does not suffer from this negative effect of the NS, as the positive value associated to the GI offset the negative effect of the NS.

Deciphering microbial communities of three Savoyard raw milk cheeses along ripening and regarding the cheese process.

Different Savoyard cheeses are granted with PDO (Protected Designation or Origin) and PGI (Protected Geographical Indication) which guarantees consumers compliance with strict specifications. The use of raw milk is known to be crucial for specific flavor development. To unravel the factors influencing microbial ecosystems across cheese making steps, according to the seasonality (winter and summer) and the mode of production (farmhouse and dairy factory ones), gene targeting on bacteria and fungus was used to have a full picture of 3 cheese making technologies, from the raw milk to the end of the ripening. Our results revealed that Savoyard raw milks are a plenteous source of biodiversity together with the brines used during the process, that may support the development of specific features for each cheese. It was shown that rinds and curds have very contrasted ecosystem diversity, composition, and evolution. Ripening stage was selective for some bacterial species, whereas fungus were mainly ubiquitous in dairy samples. All ripening stages are impacted by the type of cheese technologies, with a higher impact on bacterial communities, except for fungal rind communities, for which the technology is the more discriminant. The specific microorganism's abundance for each technology allow to see a real bar-code, with more or less differences regarding bacterial or fungal communities. Bacterial structuration is shaped mainly by matrices, differently regarding technologies while the influence of technology is higher for fungi. Production types showed 10 differential bacterial species, farmhouses showed more ripening taxa, while dairy factory products showing more lactic acid bacteria. Meanwhile, seasonality looks to be a minor element for the comprehension of both microbial ecosystems, but the uniqueness of each dairy plant is a key explicative feature, more for bacteria than for fungus communities.

Mesothelioma-Associated Fibroblasts Modulate the Response of Mesothelioma Patient-Derived Organoids to Chemotherapy via Interleukin-6.

Malignant pleural mesothelioma (MPM) remains an incurable disease. This is partly due to the lack of experimental models that fully recapitulate the complexity and heterogeneity of MPM, a major challenge for therapeutic management of the disease. In addition, the contribution of the MPM microenvironment is relevant for the adaptive response to therapy. We established mesothelioma patient-derived organoid (mPDO) cultures from MPM pleural effusions and tested their response to pemetrexed and cisplatin. We aimed to evaluate the contribution of mesothelioma-associated fibroblasts (MAFs) to the response to pemetrexed and cisplatin (P+C). Organoid cultures were obtained from eight MPM patients using specific growth media and conditions to expand pleural effusion-derived cells. Flow cytometry was used to verify the similarity of the organoid cultures to the original samples. MAFs were isolated and co-cultured with mPDOs, and the addition of MAFs reduced the sensitivity of mPDOs to P+C. Organoid formation and expression of cancer stem cell markers such as ABCG2, NANOG, and CD44 were altered by conditioned media from treated MAFs. We identified IL-6 as the major contributor to the attenuated response to chemotherapy. IL-6 secretion by MAFs is correlated with increased resistance of mPDOs to pemetrexed and cisplatin.

Sustaining altitude pastures in mountain landscapes-a fuzzy cognitive model approach.

Similarly to other European mountain areas, in Serra da Estrela the grazing pressure has been reducing due to social and economic drivers that have pushed shepherds and sheep to the foothill, or plainly out of the sector. Shrub encroachment on commons and other previously grazed land is one of the most tangible effects of pastoral abandonment in Serra de Estrela. The impacts of the resulting increase in landscape continuity and biomass availability were made clear in the severe fires of 2017 and 2022. As fire risk is likely to increase with climate change, it becomes urgent to understand what strategies can be deployed to keep fragmentation in these landscapes. Key actors such as shepherds should be involved in this discussion to understand their perceptions, points of view and reasons for abandoning upland pastures. In this study, we use fuzzy cognitive mapping to identify the key variables and mechanisms affecting the pastoral system according to local shepherds. In our study, we developed with local stakeholders a framework outlining the local pastoral system. Based on that, we carried out the fuzzy cognitive mapping collecting 14 questionnaires. We found that shepherds' income is a central issue, but that it is highly dependent on many factors. Increasing the Common Agricultural Policy payments alone is not enough to incentivise the use of upland pastures. More targeted strategies, such as more support for shrub clearing, and direct payments conditional to transhumance are more impactful. Despite a contentious discourse between conservation and shepherding values in Serra da Estrela, we find that shepherd's values are aligned with biodiversity conservation and a potential nature-based solution for minimizing fire risk through woody fuel management. This opens up possibilities for new governance strategies, that put Serra da Estrela's social, environmental and cultural values at its core.

Quality wines in Italy and France: A dataset of protected designation of origin specifications.

Italy and France are historically among the countries that produce the most prestigious wines worldwide. In Europe, these two countries together produce more than half of the wines classified under the Protected Designation of Origin (PDO) label, the strictest quality mark of food and wines in the European Union. Due to their long tradition in wine protection, Italy and France include highly detailed specifications in their wine PDO regulatory documents that are usually not available for other countries, such as specific information about the main cultivars that must be used to make each wine or the required planting density in the vineyards. However, this information is scattered throughout the documents of each wine production area and has never been extracted and homogenised in a unique dataset. Here, we present the first dataset that characterizes the PDO wines produced in Italy and France at very high detail based on the information from the official EU geographical indication register. For each country it includes a standardized list of the PDO wine names, linked with their specific requirements, such as the wine colour, type, cultivars used and maximum allowed yields. The unprecedented level of detail of this dataset allows for the first time the analysis of more than 5000 traditional wines and their legal and agronomic specifications. This gives insights into the interplay between the European Union quality regulation policy, the wine sector, and agronomic practices, enabling researchers and practitioners to analyze wine production in the context of specific regulations or economic scenarios.

Modelling esophageal adenocarcinoma and Barrett's esophagus with patient-derived organoids.

Currently, esophageal adenocarcinoma (EAC) research is hindered by a dearth of adequate models to study this disease. Traditional cell line and genetically engineered mouse models are lacking in biological and physiological significance, whilst the inefficiency of patient-derived xenografts limit their potential applications. This review describes the landscape of EAC research using patient-derived organoids (PDOs). Here, we detail the methods of establishment and optimization of EAC PDO cultures, as well as current and prospective applications of these models. We further highlight a crucial knowledge gap in the mechanisms of EAC transformation from its precursor lesion, Barrett's esophagus (BE). As such, we also describe the culture requirements of BE PDOs and attempts to model tumorigenesis using PDO models.

Development of Novel Models of Aggressive Variants of Castration-resistant Prostate Cancer.

BACKGROUND: Genomic studies have identified new subsets of aggressive prostate cancer (PCa) with poor prognosis (eg, neuroendocrine prostate cancer [NEPC], PCa with DNA damage response [DDR] alterations, or PCa resistant to androgen receptor pathway inhibitors [ARPIs]). Development of novel therapies relies on the availability of relevant preclinical models. OBJECTIVE: To develop new preclinical models (patient-derived xenograft [PDX], PDX-derived organoid [PDXO], and patient-derived organoid [PDO]) representative of the most aggressive variants of PCa and to develop a new drug evaluation strategy. DESIGN, SETTING, AND PARTICIPANTS: NEPC (n = 5), DDR (n = 7), and microsatellite instability (MSI)-high (n = 1) PDXs were established from 51 patients with metastatic PCa; PDXOs (n = 16) and PDOs (n = 6) were developed to perform drug screening. Histopathology and treatment response were characterized. Molecular profiling was performed by whole-exome sequencing (WES; n = 13), RNA sequencing (RNA-seq; n = 13), and single-cell RNA-seq (n = 14). WES and RNA-seq data from patient tumors were compared with the models. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Relationships with outcome were analyzed using the multivariable chi-square test and the tumor growth inhibition test. RESULTS AND LIMITATIONS: Our PDXs captured both common and rare molecular phenotypes and their molecular drivers, including alterations of BRCA2, CDK12, MSI-high status, and NEPC. RNA-seq profiling demonstrated broad representation of PCa subtypes. Single-cell RNA-seq indicates that PDXs reproduce cellular and molecular intratumor heterogeneity. WES of matched patient tumors showed preservation of most genetic driver alterations. PDXOs and PDOs preserve drug sensitivity of the matched tissue and can be used to determine drug sensitivity. CONCLUSIONS: Our models reproduce the phenotypic and genomic features of both common and aggressive PCa variants and capture their molecular heterogeneity. Successfully developed aggressive-variant PCa preclinical models provide an important tool for predicting tumor response to anticancer therapy and studying resistance mechanisms. PATIENT SUMMARY: In this report, we looked at the outcomes of preclinical models from patients with metastatic prostate cancer enrolled in the MATCH-R trial (NCT02517892).

The Role of Promoting Agricultural and Food Products Certified with European Union Quality Schemes.

This study delves into the effectiveness of digital marketing strategies in promoting local agricultural and food products in Romania, certified with European Union quality schemes. By examining consumer profiles, preferences, and their awareness of EU quality labels, the research uncovers the motivations driving purchasing decisions and the influence of digital marketing on these choices. Utilizing quantitative methods, including a comprehensive survey across 903 respondents, the study identifies four distinct consumer segments: Eco-Advocates, Les Connaisseurs, Price-Sensitives, and Traditionalists. These segments exhibit unique behaviors and attitudes toward certified products. The research highlights the potential of digital marketing to significantly alter consumer behavior toward EU-certified products, underscoring the importance of tailored communication strategies. It contributes to the understanding of consumer segmentation in the context of European Union quality schemes, providing valuable insights for policymakers, marketers, and producers. The findings advocate for enhanced digital marketing efforts to increase awareness and appreciation of these certified products, thereby supporting the broader objectives of quality and certification in the European agricultural and food product sector.

Advanced Facial Rejuvenation: Synergistic Effects of Lower Blepharoplasty and Ultrasound Guided Mid-Face Lift Using Polydioxanone (PDO) Threads.

BACKGROUND: Traditional facial aging surgeries have risks and extended recovery times, leading to a demand for minimally invasive alternatives. PDO (polydioxanone) threads, which are absorbable sutures that stimulate collagen production and tissue contraction, offer improved aesthetic outcomes. This paper evaluates the combined use of PDO thread mid-cheek lift and lower blepharoplasty for facial rejuvenation. METHODS: This retrospective study compared outcomes in patients undergoing lower blepharoplasty combined with a mid-face lift using PDO threads versus those undergoing only lower blepharoplasty. Focused on individuals with baggy lower eyelids and pronounced nasolabial folds, outcome measures included the Modified Fitzpatrick wrinkle scale, Allergan® midface volume deficit scale, Width of inter zygomatic distance, Patient and Observer Scar Assessment Scale, and patient satisfaction questionnaires, assessed at baseline, 3 months, and 1 year postoperatively. RESULTS: The combined procedure demonstrated superior aesthetic outcomes and higher patient satisfaction compared to lower blepharoplasty alone. Improvements were more significant in wrinkle reduction, midface volume, and inter-zygomatic distance in the combined procedure group. Although the combined procedure had a longer mean operation time, scar assessment scores were similar between both groups, with no complications reported. CONCLUSION: The combination of lower blepharoplasty and mid-face lift using PDO threads is a comprehensive and effective approach for facial rejuvenation. It significantly enhances wrinkle reduction, mid-face lifting, and patient satisfaction. Ultrasound-guided thread lifting, a method of assessing and performing mid-face lifting, proves to be safe and efficient. This approach holds promise as a future option in cosmetic anti-aging surgery, presenting a minimally invasive alternative with natural-looking results and reduced downtime. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://link.springer.com/journal/00266 .

Effect of Growing Regions on Discrimination of Turkish-Style Black Table Olives from Gemlik Cultivar.

Gemlik is a cultivar that grows in a distinct region of Turkiye and is ideal for brine fermentation of brine black table olives. Bursa Protected Designated Origin (PDO) and Izmir non-PDO Gemlik table olives have high levels of oleic acid (74%), total phenol (190 mg/kg), and dry matter (57%), while being low in linoleic acid (8%). The pH values and salt contents were observed to be in the range of 4.1 to 4.3 and 3.9% to 4.8%, respectively. During the fermentation of Gemlik table olives, a mass transfer occurred, resulting in a reduction in reducing sugar and total sugar contents as well as an increase in the salt content of the olives. Despite the reduction of phenolic content in both Gemlik PDO and non-PDO table olives, their antioxidant capacity remains high after fermentation. The oil content, antioxidant activity, phenolic contents, palmitic, palmitoleic, oleic, and linoleic acids were all found to be significant variables in distinguishing between Gemlik PDO and non-PDO table olives using PLS-DA analysis. There is a statistically significant correlation between the phenolic content and oleic (0.588) and linoleic (-0.659) acids (p < 0.05). Bursa PDO and Izmir non-PDO exhibit enhanced nutritional quality and antioxidant activity, unequivocally differentiating them from Hatay and Mersin non-PDO Gemlik table olives with 98% accuracy through discriminant analysis (p < 0.05). PLS-DA and DA can effectively identify variations in the quality of Turkish-style black table olives preserved in brine, originating from PDO and non-PDO growing areas.

Sustainability implications and relevance of using omics sciences to investigate cheeses with protected designation of origin.

Cheese, a fundamental component of the human diet and a cornerstone of the global food economy, has a significance beyond its role as a commodity, playing a crucial part in the cultural identity of various communities. The intricate natural aging process known as maturation involves a series of reactions that induce changes in the cheese's physical, biochemical, microbiological, and particularly sensory characteristics, making it a complex aspect of cheese production. Recently, the adoption of omics sciences (e.g., metagenomics, metabolomics, proteomics) has emerged as a new trend in studies related to protected designation of origin (PDO) cheese. This mini-summary aims to outline the relationship between omics studies in these food matrices and all the sustainability facets of the production chain in general, and to discuss and recognize that the importance of these studies goes beyond comprehending the cheese biome and extends to fostering and ensuring the sustainability of the production chain. In this context, numerous studies in recent years have linked the identification of intrinsic characteristics of PDO cheeses through omics sciences to crucial sustainability themes such as territoriality, biodiversity, and the preservation of product authenticity. The trajectory suggests that, increasingly, multidisciplinary studies spanning various omics sciences will not only contribute to the characterization of these products but will also address sustainability aspects directly related to the production chain (e.g., authenticity, microbial biodiversity, functionality). This expansion underscores the multidisciplinary nature of these studies, broadening their social impact beyond the academic realm. Consequently, these pivotal studies play a crucial role in advancing discussions on PDO products and sustainability. © 2024 Society of Chemical Industry.

Chromatin Remodeling in Patient-Derived Colorectal Cancer Models.

Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the transcriptomic and chromatin accessibility landscapes of matched colorectal cancer (CRC) PDO, PDX, PDO-derived PDX (PDOX), and original patient tumors (PT) are compared. Two major remodeling axes are discovered. The first axis delineates PDMC from PT, and the second axis distinguishes PDX and PDO. PDOX are more similar to PDX than PDO, indicating the growth environment is a driving force for chromatin adaptation. Transcription factors (TF) that differentially bind to open chromatins between matched PDO and PDOX are identified. Among them, KLF14 and EGR2 footprints are enriched in PDOX relative to matched PDO, and silencing of KLF14 or EGR2 promoted tumor growth. Furthermore, EPHA4, a shared downstream target gene of KLF14 and EGR2, altered tumor sensitivity to MEK inhibitor treatment. Altogether, patient-derived CRC cells undergo both common and distinct chromatin remodeling in PDO and PDX/PDOX, driven largely by their respective microenvironments, which results in differences in growth and drug sensitivity and needs to be taken into consideration when interpreting their ability to predict clinical outcome.

Effectiveness of modified atmosphere and vacuum packaging in preserving the volatilome of Stelvio PDO cheese over time.

We aimed to assay the effectiveness of vacuum or modified atmosphere packaging in preserving the organoleptic characteristics of already ripened slices of Stelvio Protected Designation of Origin cheese during 3 months of storage. A multi-omics panel, including metagenomic and metabolomic analyses, was implemented together with physicochemical and sensory analyses. Among the 177 volatiles identified, 30 out of the 50 potent odorants were found to be prevalent, regardless of packaging. Isovaleric acid showed the highest relative intensity in all samples. Caproic and caprylic acids always increased during storage, while metabolites such as dodecane and 2,3-butanediol always decreased. Slow proteolysis occurred during storage, but did not differentiate cheese samples. The type of packaging differentiated the microbiota and volatile profile, with modified atmosphere packaging keeping the volatilome more stable. Out of the 50 potent odorants, 9 were relevant to sample discrimination, with 8-nonen-2-one, 2-nonanone, and caproic acid being more abundant in stored samples.

Toxoflavin analog D43 exerts antiproliferative effects on breast cancer by inducing ROS-mediated apoptosis and DNA damage.

Triple-negative breast cancer (TNBC) is regarded as the deadliest subtype of breast cancer because of its high heterogeneity, aggressiveness, and limited treatment options. Toxoflavin has been reported to possess antitumor activity. In this study, a series of toxoflavin analogs were synthesized, among which D43 displayed a significant dose-dependent inhibitory effect on the proliferation of TNBC cells (MDA-MB-231 and HCC1806). Additionally, D43 inhibited DNA synthesis in TNBC cells, leading to cell cycle arrest at the G2/M phase. Furthermore, D43 consistently promoted intracellular ROS generation, induced DNA damage, and resulted in apoptosis in TNBC cells. These effects could be reversed by N-acetylcysteine. Moreover, D43 significantly inhibited the growth of breast cancer patient-derived organoids and xenografts with a favorable biosafety profile. In conclusion, D43 is a potent anticancer agent that elicits significant antiproliferation, oxidative stress, apoptosis, and DNA damage effects in TNBC cells, and D43 holds promise as a potential candidate for the treatment of TNBC.