Water-Soluble Curcumin Derivatives Including Aza-Crown Ether Macrocycles as Enhancers of their Cytotoxic Activity.

The synthesis of three novel curcumin derivative compounds, featuring aza-crown ether macrocycles of various sizes (aza-12-crown-4, aza-15-crown-5, and aza-18-crown-6), is described. The incorporation of these aza-crown macrocycles significantly enhances their water solubility, positioning them as groundbreaking instances of curcumin derivatives that are fully soluble in aqueous environments. These curcumin ligands (L1, L2, and L3) were then reacted with zinc acetate to afford the coordination metal complexes (L1-Zn, L2-Zn, and L3-Zn). Comprehensive characterization of all compounds was achieved using various analytical techniques, including 1D and 2D NMR spectroscopy, ATR-FTIR spectroscopy, mass spectrometry (ESI+), elemental analysis and UV-Vis spectroscopy. The in vitro cytotoxic activity of both, ligands and complexes were evaluated on three human cancer cell lines (U-251, MCF-7, and SK-LU-1). Compared to conventional curcumin, these compounds demonstrated improved antiproliferative potential. Additionally, a wound healing assay was conducted to assess their antimigration properties. The obtained results suggest that these modifications to the curcumin structure represent a promising approach for developing therapeutic agents with enhanced cytotoxic properties.

Methylation Clocks Do Not Predict Age or Alzheimer's Disease Risk Across Genetically Admixed Individuals.

Epigenetic clocks that quantify rates of aging from DNA methylation patterns across the genome have emerged as a potential biomarker for risk of age-related diseases, like Alzheimer's disease (AD), and environmental and social stressors. However, methylation clocks have not been validated in genetically diverse cohorts. Here we evaluate a set of methylation clocks in 621 AD patients and matched controls from African American, Hispanic, and white cohorts. The clocks are less accurate at predicting age in genetically admixed individuals, especially those with substantial African ancestry, than in the white cohort. The clocks also do not consistently identify age acceleration in admixed AD cases compared to controls. Methylation QTL (meQTL) commonly influence CpGs in clocks, and these meQTL have significantly higher frequencies in African genetic ancestries. Our results demonstrate that methylation clocks often fail to predict age and AD risk beyond their training populations and suggest avenues for improving their portability.

Seaweeds as holobionts: Current state, challenges, and potential applications.

Seaweeds play a strong ecological and economical role along the world's coastlines, where they support industries (e.g., aquaculture, bioproducts) and essential ecosystem services (e.g., biodiversity, fisheries, carbon capture). Evidence from wild and cultured seaweeds suggests that microorganisms play crucial roles in their health and functioning, prompting the need for considering seaweeds and their microbiome as a coherent entity or "holobiont." Here we show that the number of studies investigating seaweed hosts and their microbiome have increased in the last two decades. This likely reflects the increase in the appreciation of the importance of microbiomes for eukaryotic hosts, improved molecular approaches used to characterize their interactions, and increasing interest in commercial use of seaweeds. However, although increasing, most studies of seaweed holobionts have focused on (i) a few seaweed species of ecological or commercial significance, (ii) interactions involving only bacteria, and (iii) descriptive rather than experimental approaches. The relatively few experimental studies have mostly focused on manipulating abiotic factors to examine responses of seaweeds and their microbiome. Of the few studies that directly manipulated microorganisms to investigate their effects on seaweeds, most were done in laboratory or aquaria. We emphasize the need to move beyond the descriptions of patterns to experimental approaches for understanding causation and mechanisms. We argue that such experimental approaches are necessary for a better understanding of seaweed holobionts, for management actions for wild and cultivated seaweeds, and to better integrate studies of seaweed holobionts with the broader fields of seaweed ecology and biology, which are strongly experimental.

Synthesis of Para-Acetylated Functionalized Ni(II)-POCOP Pincer Complexes and Their Cytotoxicity Evaluation Against Human Cancer Cell Lines.

A series of three Ni(II)-POCOP complexes para-functionalized with an acetoxyl fragment were synthesized. All complexes (2 a-c) were fully characterized through standard analytical techniques. The molecular structure of complex 2 b was unambiguously determined by single-crystal X-ray diffraction, revealing that the metal center is situated in a slightly distorted square-planar environment. Additionally, the acetoxy fragment at the para-position of the phenyl ring was found to be present. The in vitro cytotoxic activity of all complexes was assessed on six human cancer cell lines. Notably, complex 2 b exhibited selective activity against K-562 (chronic myelogenous leukemia) and MCF-7 (mammary adenocarcinoma) with IC50 values of 7.32±0.60 µM and 14.36±0.02 µM, respectively. Furthermore, this compound showed negligible activity on the healthy cell line COS-7, highlighting the potential therapeutic application of 2 b. The cytotoxic evaluations were further complemented with molecular docking calculations to explore the potential biological targets of complex 2 b, revealing interactions with cluster differentiation protein 1a (CD1 A, PDB: 1xz0) for K-562 and with the progesterone receptor for MCF-7.

Selective Antineoplastic Potential of Fractionated Caribbean Native Ganoderma Species Extracts on Triple-Negative Breast Cancer Cells.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2 expression. It is known for its high malignancy, invasiveness, and propensity for metastasis, resulting in a poor prognosis due to the absence of beneficial therapeutic targets. Natural products derived from mushrooms have gained significant attention in neoplastic therapy due to their potential medicinal properties. The therapeutic potential of Ganoderma lucidum in breast cancer has been highlighted by our group, suggesting its use as an adjuvant treatment. The present study aims to assess the potential antineoplastic capacity of two Caribbean native Ganoderma species found in Puerto Rico, Ganoderma multiplicatum (G. multiplicatum) and Ganoderma martinicense (G. martinicense). Antiproliferative studies were conducted via cell viability assays after cultivation, harvesting, and fractionation of both species. The obtained results indicate that most of the fractions show some cytotoxicity against all cell lines, but 33% of the fractions (F1, F2, F7, F12) display selectivity towards cancer cell models. We demonstrate for the first time that native Ganoderma species can generate metabolites with anti-TNBC properties. Future avenues will focus on structure elucidation of the most active fractions of these Ganoderma extracts.

Child and adolescent victims of sexual homicide in Chile between 1998 and 2021: A review of 27 cases and their autopsy reports.

Rape followed by murder against children and adolescents is one of the most serious existing crimes. The autopsies of victims of violent crimes can provide fundamental findings for the investigative process and the pursuit of justice. This research conducts a descriptive analysis of the most important findings from the autopsies of 27 cases of children and adolescents who died in Chile between 1998 and 2021 as a result of rape followed by homicide (n = 27), as well as from the judiciary rulings of these cases to gather information related to the perpetrators. It was found that the victims of this crime are mostly girls with an average age of 10, while the perpetrators are primarily single men aged 29 on average, most of whom have not finished high school. A significant relationship was found between the location of the crime and the cause of death and signs of sexual contact, the marital status of the perpetrator and the cause of death, the age of the perpetrator and signs of sexual contact, and the relationship between victim and perpetrator and signs of sexual contact.

Toward biomanufacturing of next-generation bacterial nanocellulose (BNC)-based materials with tailored properties: A review on genetic engineering approaches.

Bacterial nanocellulose (BNC) is a biopolymer that is drawing significant attention for a wide range of applications thanks to its unique structure and excellent properties, such as high purity, mechanical strength, high water holding capacity and biocompatibility. Nevertheless, the biomanufacturing of BNC is hindered due to its low yield, the instability of microbial strains and cost limitations that prevent it from being mass-produced on a large scale. Various approaches have been developed to address these problems by genetically modifying strains and to produce BNC-based biomaterials with added value. These works are summarized and discussed in the present article, which include the overexpression and knockout of genes related and not related with the nanocellulose biosynthetic operon, the application of synthetic biology approaches and CRISPR/Cas techniques to modulate BNC biosynthesis. Further discussion is provided on functionalized BNC-based biomaterials with tailored properties that are incorporated in-vivo during its biosynthesis using genetically modified strains either in single or co-culture systems (in-vivo manufacturing). This novel strategy holds potential to open the road toward cost-effective production processes and to find novel applications in a variety of technology and industrial fields.

Biological activity of the essential oil of Drimys winteri.

In the Chilean indigenous culture, the tree Drimys winteri (Winteraceae) Canelo is of great importance and is considered the sacred Mapuche tree. It has antibacterial and disinfectant properties and is used in the treatment of various diseases, such as fevers, ulcers, cancers, and respiratory tract problems. The essential oil obtained from D. winteri, DW_EO, is bioactive, possesses insecticidal and repellent properties against pests, and shows activity toward plant growth regulators. It also has a phytotoxic effect against the growth and germination of weeds. The essential oil obtained from the leaves and bark of Drimys winteri has demonstrated antifungal, immunomodulatory, anti-inflammatory, and anticancer properties in in vitro and in vivo studies. It also possesses antioxidant activity and antibacterial effects. The essential oil contains monoterpenes such as zafrol, pinenes, and linalool, among others, that contribute to its bioactivity. The DW_EO and bioactive compounds have great potential in various applications in medicine, industrial food, sanitizer, and other areas.

Disentangling direct vs indirect effects of microbiome manipulations in a habitat-forming marine holobiont.

Host-associated microbiota are critical for eukaryotic host functioning, to the extent that hosts and their associated microbial communities are often considered "holobionts". Most studies of holobionts have focused on descriptive approaches or have used model systems, usually in the laboratory, to understand host-microbiome interactions. To advance our understanding of host-microbiota interactions and their wider ecological impacts, we need experimental frameworks that can explore causation in non-model hosts, which often have highly diverse microbiota, and in their natural ecological setting (i.e. in the field). We used a dominant habitat-forming seaweed, Hormosira banksii, to explore these issues and to experimentally test host-microbiota interactions in a non-model holobiont. The experimental protocols were aimed at trying to disentangle microbially mediated effects on hosts from direct effects on hosts associated with the methods employed to manipulate host-microbiota. This was done by disrupting the microbiome, either through removal/disruption using a combination of antimicrobial treatments, or additions of specific taxa via inoculations, or a combination of thew two. The experiments were done in mesocosms and in the field. Three different antibiotic treatments were used to disrupt seaweed-associated microbiota to test whether disturbances of microbiota, particularly bacteria, would negatively affect host performance. Responses of bacteria to these disturbances were complex and differed substantially among treatments, with some antibacterial treatments having little discernible effect. However, the temporal sequence of responses antibiotic treatments, changes in bacterial diversity and subsequent decreases in host performance, strongly suggested an effect of the microbiota on host performance in some treatments, as opposed to direct effects of the antibiotics. To further test these effects, we used 16S-rRNA-gene sequencing to identify bacterial taxa that were either correlated, or uncorrelated, with poor host performance following antibiotic treatment. These were then isolated and used in inoculation experiments, independently or in combination with the previously used antibiotic treatments. Negative effects on host performance were strongest where specific microbial antimicrobials treatments were combined with inoculations of strains that were correlated with poor host performance. For these treatments, negative host effects persisted the entire experimental period (12 days), even though treatments were only applied at the beginning of the experiment. Host performance recovered in all other treatments. These experiments provide a framework for exploring causation and disentangling microbially mediated vs. direct effects on hosts for ecologically important, non-model holobionts in the field. This should allow for better predictions of how these systems will respond to, and potentially mitigate, environmental disturbances in their natural context.

TIROSEC: Molecular, Clinical and Histopathological Profile of Papillary Thyroid Carcinoma in a Colombian Cohort.

INTRODUCTION: In Colombia, thyroid cancer ranks among the highest incidences, yet our population lacks studies on its molecular profile. This study aims to characterize clinical, histopathologic and molecular data in a Colombian cohort with papillary thyroid carcinoma (PTC). METHODS: A retrospective review of clinical history, clinicopathologic characteristics, treatment and 5-10-year follow-up for all patients was done. DNA and RNA were extracted from formalin-fixed paraffin-embedded (FFPE) tissue using the Quick-DNA & RNA FFPE Min iPrep kit (Zymo Research). Next-generation sequencing (NGS) analysis was performed with SOPHiA Solid Tumor Solutions kit (SOPHiA GENETICS). Tumor mutation genomic analysis used SOPHiA DDM™ platform, with descriptive analysis reporting frequencies, means and associations via chi-square analysis. RESULTS: Among 231 sequenced patients, mean age at diagnosis was 46 (± 12.35) years, with higher frequency in women (81.82%). Two cases were reclassified as non-invasive follicular thyroid neoplasm (NIFT-P); an NRAS mutation was found in one of them. Predominant histologic subtype was classic PTC (57.64%) followed by tall cell (28.82%). Of the 229 sequenced carcinomas, mutations were identified in 186 cases, including BRAF, IDH1, RAS and PIK3CA. Notable copy number variations (CNVs) were PDGFRA, CDK4 and KIT, with RET being the most frequent gene fusion, including CCDC6-RET in two classic subtype cases. CONCLUSION: This is the first study in Colombia (TIROSEC) to our knowledge that integrates molecular and histopathologic profiles enriching our local comprehension and knowledge of PTC. The identification of target mutations such as BRAF, RET and NTRK fusions holds the potential to guide targeted therapies for tumor recurrence and predict aggressive behavior.

Evaluation of an automatized AMBU ESSI-1 INC designed at the Instituto Nacional de Cardiología Ignacio Chávez / Evaluación del AMBU automatizado ESSI-1 INC diseñado en el Instituto Nacional de Cardiología Ignacio Chávez

Abstract Objective: The objectives of this study were to evaluate an automated device for ventilatory support based on AMBU manufactured in March 2020. Methods: The ESSI-1 INC was evaluated through pulmonary mechanics and physiology parameters through compensatory spirometer tests (TISSOTs), and an artificial lung Model5600i Dual Adult PNEU VIEW SYSTEM; it was also compared to the anesthetic ventilatory support equipment (AEONMED 7500) in porcine models, measuring ventilatory, hemodynamic and gasometric parameters. Results: This equipment (ESSI-1 INC) was successfully tested by mechanical and biological models, such as pigs in which its performance was evaluated in terms of variability of tidal volume, ventilation frequency, and I/E relationship versus the manual performance of two medical interns. All the results turned out as expected and were satisfactory. Conclusions: It is safe and effective equipment and should be tested and used in diverse clinical conditions to standardize the ventilatory safety and care of patients who require it.

Resumen Objetivo: Evaluar un dispositivo automatizado para la asistencia ventilatoria basado en un AMBU manufacturado en Marzo del 2020. Métodos: El ESSI-1 INC fue evaluado por medio de parámetros fisiológicos y mecánica pulmonar a través de pruebas de espirómetro compensatorios (TISSOT); pulmón artificial (Modelo 5600i Dual Adult PNEU VIEW SYSTEM); así como su desempeño comparado a la máquina de anestesia (AEONMED 7500) en modelos porcinos, midiendo criterios ventilatorios, hemodinámicos y gasométricos. Resultados: Este equipo (ESSI-1 INC) fue exitosamente probado por modelos mecánicos y biológicos, tales como cerdos donde su desempeño fue evaluado en términos de la variabilidad del volumen tidal, frecuencia ventilatoria, y relación I/E versus el desempeño manual de dos médicos. Todos los resultados finalizaron como se esperaba de forma satisfactoria. Conclusiones: Es un equipo seguro y efectivo, el cual debería ser probado y usado en distintas condiciones clínicas para estandarizar la seguridad ventilatoria y cuidado de pacientes que lo requieran.

Method for Extraction and Evaluation of Heliocarpus popayanensis and Triumfetta bogotensis as Natural Coagulants for the Treatment of Wastewater.

This research evaluates extracts from the bark of Heliocarpus popayanensis and Triumfetta bogotensis as coagulating agents for removing turbidity in domestic wastewater, considering the coagulant dosage and pH of the wastewater. ANOVA was conducted to assess differences between the coagulants, dosages, and pH, with three pH levels (5, 8, and 9) and six dosages (7, 9, 11, 13, 15, and 17 mL per 1000 mL of wastewater) at a significance level of α = 0.05, and both the p-value and effect size were evaluated. This study found that the mucilaginous compound from the bark of Triumfetta bogotensis performed better in reducing turbidity levels, with an average reduction of 30.2 NTU (Nephelometric Turbidity Unit) (CI [25.9 NTU; 34.5 NTU], α = 0.05) at a pH of 5, and an average initial NTU of 102.2. This represents an average reduction of 70.45%. The dosage factor did not show significant effects on turbidity reduction, which opens the possibility for further study to determine the optimal dosage of the best coagulant.

Evaluation of an automatized AMBU ESSI-1 INC designed at the Instituto Nacional de Cardiología Ignacio Chávez.

OBJECTIVE: The objectives of this study were to evaluate an automated device for ventilatory support based on AMBU manufactured in March 2020. METHODS: The ESSI-1 INC was evaluated through pulmonary mechanics and physiology parameters through compensatory spirometer tests (TISSOTs), and an artificial lung Model5600i Dual Adult PNEU VIEW SYSTEM; it was also compared to the anesthetic ventilatory support equipment (AEONMED 7500) in porcine models, measuring ventilatory, hemodynamic and gasometric parameters. RESULTS: This equipment (ESSI-1 INC) was successfully tested by mechanical and biological models, such as pigs in which its performance was evaluated in terms of variability of tidal volume, ventilation frequency, and I/E relationship versus the manual performance of two medical interns. All the results turned out as expected and were satisfactory. CONCLUSIONS: It is safe and effective equipment and should be tested and used in diverse clinical conditions to standardize the ventilatory safety and care of patients who require it.

OBJETIVO: Evaluar un dispositivo automatizado para la asistencia ventilatoria basado en un AMBU manufacturado en Marzo del 2020. MÉTODOS: El ESSI-1 INC fue evaluado por medio de parámetros fisiológicos y mecánica pulmonar a través de pruebas de espirómetro compensatorios (TISSOT); pulmón artificial (Modelo 5600i Dual Adult PNEU VIEW SYSTEM); así como su desempeño comparado a la máquina de anestesia (AEONMED 7500) en modelos porcinos, midiendo criterios ventilatorios, hemodinámicos y gasométricos. RESULTADOS: Este equipo (ESSI-1 INC) fue exitosamente probado por modelos mecánicos y biológicos, tales como cerdos donde su desempeño fue evaluado en términos de la variabilidad del volumen tidal, frecuencia ventilatoria, y relación I/E versus el desempeño manual de dos médicos. Todos los resultados finalizaron como se esperaba de forma satisfactoria. CONCLUSIONES: Es un equipo seguro y efectivo, el cual debería ser probado y usado en distintas condiciones clínicas para estandarizar la seguridad ventilatoria y cuidado de pacientes que lo requieran.

Organic enrichment reduces sediment bacterial and archaeal diversity, composition, and functional profile independent of bioturbator activity.

Eutrophication is a worldwide issue that can disrupt ecosystem processes in sediments. Studies have shown that macrofauna influences sediment processes by engineering environments that constrain microbial communities. Here, we explored the effect of different sizes of the Sydney cockle (Anadara trapezia), on bacterial and archaeal communities in natural and experimentally enriched sediments. A mesocosm experiment was conducted with two enrichment conditions (natural or enriched) and 5 cockle treatments (small, medium, large, mixed sizes and a control). This study was unable to detect A. trapezia effects on microbial communities irrespective of body size. However, a substantial decrease of bacterial richness, diversity, and structural and functional shifts, were seen with organic enrichment of sediments. Archaea were similarly changed although the magnitude of effect was less than for bacteria. Overall, we found evidence to suggest that A. trapezia had limited capacity to affect sediment microbial communities and mitigate the effects of organic enrichment.

Model-predicted geometry variations to compensate material variability in the design of classical guitars.

Musical instrument making is often considered a mysterious form of art, its secrets still escaping scientific quantification. There is not yet a formula to make a good instrument, so historical examples are regarded as the pinnacle of the craft. This is the case of Stradivari's violins or Torres guitars that serve as both models and examples to follow. Geometric copies of these instruments are still the preferred way of building new ones, yet reliably making acoustic copies of them remains elusive. One reason for this is that the variability of the wood used for instruments makes for a significant source of uncertainty-no two pieces of wood are the same. In this article, using state-of-the-art methodologies, we show a method for matching the vibrational response of two guitar top plates made with slightly different materials. To validate our method, we build two guitar soundboards: one serving as a reference and the second acting as a copy to which we apply model-predicted geometry variations. The results are twofold. Firstly, we can experimentally validate the predictive capabilities of our numerical model regarding geometry changes. Secondly, we can significantly reduce the deviation between the two plates by these precisely predicted geometry variations. Although applied to guitars here, the methodology can be extended to other instruments, e.g. violins, in a similar fashion. The implications of such a methodology for the craft could be far-reaching by turning instrument-making more into a science than artistic craftsmanship and paving the way to accurately copy historical instruments of a high value.

A neural network-based method for spruce tonewood characterization.

The acoustical properties of wood are primarily a function of its elastic properties. Numerical and analytical methods for wood material characterization are available, although they are either computationally demanding or not always valid. Therefore, an affordable and practical method with sufficient accuracy is missing. In this article, we present a neural network-based method to estimate the elastic properties of spruce thin plates. The method works by encoding information of both the eigenfrequencies and eigenmodes of the system and using a neural network to find the best possible material parameters that reproduce the frequency response function. Our results show that data-driven techniques can speed up classic finite element model updating by several orders of magnitude and work as a proof of concept for a general neural network-based tool for the workshop.

Assessing the Feasibility and Acceptability of a Primary Care Socio-Ecological Approach to Improve Physical Activity Adherence among People with Type 2 Diabetes: The SENWI Project.

Maintaining an active lifestyle is a key health behavior in people with type 2 diabetes (T2D). This study assessed the feasibility and acceptability of a socio-ecological Nordic walking intervention (SENWI) to enhance healthy behaviors in primary healthcare settings. Participants included individuals with T2D (n = 33; age 70 (95% CI 69-74)) and healthcare professionals (HCPs, n = 3). T2D participants were randomly assigned to a SENWI, active comparator, or control group for twelve weeks. Feasibility and acceptability were evaluated based on a mixed methodology. Quantitative data reported adherence information, differences between follow-up and dropout participants and pre- and post-intervention on physical activity, sedentary behavior, and health outcomes. Qualitative data acquisition was performed using focus groups and semi-structured interviews and analyzed using thematic analysis. Thirty-three T2D invited participants were recruited, and twenty-two (66.7%) provided post-intervention data. The SENWI was deemed acceptable and feasible, but participants highlighted the need to improve options, group schedules, gender inequities, and the intervention's expiration date. Healthcare professionals expressed a lack of institutional support and resources. Nevertheless, no significant difference between the SENWI follow-up and dropout participants or pre- and post- intervention was found (only between the active comparator and control group in the physical quality of life domain). Implementing the SENWI in primary healthcare settings is feasible and acceptable in real-world conditions. However, a larger sample is needed to assess the program's effectiveness in improving healthy behaviors and its impact on health-related outcomes in the long term.

Host genotype and microbiome associations in co-occurring clonal and non-clonal kelp, Ecklonia radiata.

A fundamental question in holobiont biology is the extent to which microbiomes are determined by host characteristics regulated by their genotype. Studies on the interactions of host genotype and microbiomes are emerging but disentangling the role that host genotype has in shaping microbiomes remains challenging in natural settings. Host genotypes tend to be segregated in space and affected by different environments. Here we overcome this challenge by studying an unusual situation where host asexual (5 clonal lineages) and sexual genotypes (15 non-clonal lineages) of the same species co-occur under the same environment. This allowed us to partition the influence of morphological traits and genotype in shaping host-associated bacterial communities. Lamina-associated bacteria of co-occurring kelp sexual non-clonal (Ecklonia radiata) and asexual clonal (E. brevipes) morphs were compared to test whether host genotype influences microbiomes beyond morphology. Similarity of bacterial composition and predicted functions were evaluated among individuals within a single clonal genotype or among non-clonal genotypes of each morph. Higher similarity in bacterial composition and inferred functions were found among identical clones of E. brevipes compared to other clonal genotypes or unique non-clonal E. radiata genotypes. Additionally, bacterial diversity and composition differed significantly between the two morphs and were related with one morphological trait in E. brevipes (haptera). Thus, factors regulated by the host genotype (e.g. secondary metabolite production) likely drive differences in microbial communities between morphs. The strong association of genotype and microbiome found here highlights the importance of genetic relatedness of hosts in determining variability in their bacterial symbionts.