Metal accumulation in female green sea turtles (Chelonia mydas) from Eastern Atlantic affects their egg quality with potential implications for embryonic development.

Sea turtles, with their global distribution and complex life cycle, often accumulate pollutants such as metals and metalloids due to their extended lifespan and feeding habits. However, there are limited studies exploring the impact of metal pollution on the reproductive health of female sea turtles, specifically focusing on the quality of their eggs, which has significant implications for the future generations of these charismatic animals. São Tomé Island, a crucial nesting and feeding habitat for green sea turtles, underscores the urgent need for comprehensive research in this ecologically significant area. This study aimed to investigate whether metals and metalloids in the blood of nesting female green sea turtles induce genotoxic effects in their erythrocytes and affect their egg morphometric characteristics and the composition of related compartments. Additionally, this study aimed to evaluate whether the quality of energetic reserves for embryo development (fatty acids in yolk's polar and neutral lipids) is influenced by the contamination status of their predecessors. Results revealed correlations between Cu and Hg levels and increased "lobed" erythrocytes, while As and Cu negatively influenced shell thickness. In terms of energy reserves, both polar and neutral lipid fractions contained primarily saturated and monounsaturated fatty acids, with prevalent 18:1n-9, 18:0, 16:0, 14:0, and 12:0 fatty acids in yolk samples. The yolk polar fraction was more susceptible to contaminant levels in female sea turtles, showing consistent negative correlations between pollution load index and essential n3 fatty acids, including linolenic, eicosatrienoic, eicosapentaenoic, and docosapentaenoic acids, crucial for embryonic development. These metals accumulation, coupled with the reduced availability of these key fatty acids, may disrupt the eicosanoid and other important pathways, affecting reproductive development. This study reveals a negative correlation between metal contamination in female sea turtles' blood and egg lipid reserves, raising concerns about embryonic development and the species' future generations.

Novel WRN Helicase Inhibitors Selectively Target Microsatellite Unstable Cancer Cells.

Microsatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n-dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumours, and WRN inhibitors are in development. Here, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target. Fragment-based screening led to the development of potent and highly selective WRN helicase covalent inhibitors. These compounds selectively suppressed MSI model growth In vitro and In vivo by mimicking WRN loss, inducing DNA double-strand breaks at expanded TA-repeats and DNA damage. Assessment of biomarkers in preclinical models linked TA-repeat expansions and mismatch repair (MMR) alterations to compound activity. Efficacy was confirmed in immunotherapy-resistant organoids and patient-derived xenograft (PDX) models. The discovery of potent, selective covalent WRN inhibitors provides proof of concept for synthetic-lethal targeting of WRN in MSI cancer and tools to dissect WRN biology.

Green and Hawksbill Sea turtles of Eastern Atlantic: New insights into a globally important rookery in the Gulf of Guinea.

Sea turtles are critical components of marine ecosystems, and their conservation is important for Ocean Governance and Global Planet Health. However, there is limited knowledge of their ecology in the Gulf of Guinea. To fill this knowledge gap, this study presents the first integrative assessment of green and hawksbill turtles in the region, combining nesting surveys over 9 years and telemetry data, to offer insights into these population dynamics, and behaviours, including nesting preferences, morphological and reproductive parameters, diving patterns and inter-nesting core-use areas. Both green and hawksbill turtles are likely making a recovery on São Tomé, potentially driven by sustained conservation efforts. There are preliminary indications of recovery, but we interpret this cautiously. Coupled with satellite tracking, this study estimated that 482 to 736 green turtles and 135 to 217 hawksbills nest on the beaches of São Tomé. Their movements overlap significantly with a proposed Marine Protected Area (MPA), which suggests they may be well placed for conservation if managed appropriately. However, the presence of artisanal fisheries and emerging threats, such as sand mining and unregulated tourism, highlight the urgent need for robust management strategies that align global conservation objectives with local socioeconomic realities. This study significantly enhances our understanding of the ecology and conservation needs of the green and hawksbill turtles in the Gulf of Guinea. The insights gleaned here can contribute to the development of tailored conservation strategies that benefit these populations and the ecosystem services upon which they depend.

A Change of Paradigm in the Management of Acute Psychiatric Episodes? A Retrospective Cohort Study on Trajectories of Use of Clinical Resources After the Implementation of Intensive Home-Treatment.

Intensive home treatment (IHT) has shown to be a feasible alternative to hospitalization for the management of acute psychiatric episodes, but there are no real-world studies assessing if patients with a first IHT use it again for the management of their recurrences. The objectives of this retrospective cohort study were to map the use ofacute treatment resources after the implementation of IHT in our territory through the establishment of trajectories of management, and to disentangle if there are profiles of patients who fit better each trajectory. We included the first 1000 episodes admitted to IHT, of which we selected those that corresponded to the first IHT of a patient (index admission). Trajectories after the index admission were: (T-A) absence of use of acute resources, (T-B) only IHT, and (T-C) at least one hospitalization. Follow-up ranged from 6 months to 6 years. We calculated the frequency of each trajectory and performed univariate analyses searching for associations between trajectory and clinical factors. Among those patients with psychiatric history (N = 659), 66.2% followedT-A, 11.2% T-B, and 22.6% T-C. The probability of following T-C was higher for patients with a psychotic disorder (pBonf = 0.018) and with previous hospitalizations (pBonf < 0.0001). Among those patients without psychiatric history (N = 168), 82.7% followed T-A, 6.6% T-B, and 10.7% T-C. The probability of following T-B was higher for those with a higher severity at the index admission (pBonf = 0.028). This study shows that some -or even all- recurrences of some subjects were successfully managed with IHT, providing real-world evidence for its use in acute psychiatric conditions.

Antioxidant and Anti-Inflammatory Activities of Stellera chamaejasme L. Roots and Aerial Parts Extracts.

Natural products, mainly plants, have a crucial role in folk medicine. Particularly, Stellera chamaejasme L. has been traditionally used in Mongolian medicine to treat various diseases, including chronic tracheitis, tuberculosis, and psoriasis. In this study, ethanol (EtOH) and dichloromethane (DCM) extracts of its roots (R) and aerial parts (AP) were evaluated for their antioxidant and anti-inflammatory activities. Thin-layer chromatography demonstrated the presence of flavonoids, namely kaempferol and quercetin-3-O-glucopyranoside, only in the EtOH-AP. Conversely, it showed that kaempferol, quercetin-3-O-glucopyranoside, coumarin, luteolin, rutin, morin, and riboflavin were not present in the other three extracts. The S. chamaejasme extracts exhibited strong antioxidant activity. In addition, the roots extracts presented the highest antioxidant activity against peroxyl radicals, with the EtOH-R being the most potent (IC50 = 0.90 ± 0.07 µg/mL). S. chamaejasme extracts also efficiently inhibited the production of one of the main pro-inflammatory cytokines, interleukin (IL)-6, in a dose-dependent manner by lipopolysaccharide-stimulated macrophages. Particularly, DCM-R was the strongest extract, reducing ≈ 91.5% of the IL-6 production. Since this extract was the most effective, gas chromatography-mass spectrometry (GC-MS) analyses were performed and demonstrated the presence of two fatty acids (palmitic acid and 9-octadecenoic acid), one fatty alcohol (1-hexadecanol), and one triterpenoid (squalene) that can contribute to the observed bioactivity. Herewith, S. chamaejasme extracts, mainly DCM-R, exhibit antioxidant and anti-inflammatory activities that could be applied as new and innovative natural formulations for the treatment of chronic inflammatory diseases.

Synthesis and Anti-Inflammatory Evaluation of a Library of Chiral Derivatives of Xanthones Conjugated with Proteinogenic Amino Acids.

In recent decades, the relationship between drug chirality and biological activity has been assuming enormous importance in medicinal chemistry. Particularly, chiral derivatives of xanthones (CDXs) have interesting biological activities, including enantioselective anti-inflammatory activity. Herein, the synthesis of a library of CDXs is described, by coupling a carboxyxanthone (1) with both enantiomers of proteinogenic amino esters as chiral building blocks (2-31), following the chiral pool strategy. The coupling reactions were performed at room temperature with good yields (from 44 to 99.9%) and very high enantiomeric purity, with most of them presenting an enantiomeric ratio close to 100%. To afford the respective amino acid derivatives (32-61), the ester group of the CDXs was hydrolyzed in mild alkaline conditions. Consequently, in this work, sixty new derivatives of CDXs were synthetized. The cytocompatibility and anti-inflammatory activity in the presence of M1 macrophages were studied for forty-four of the new synthesized CDXs. A significant decrease in the levels of a proinflammatory cytokine targeted in the treatment of several inflammatory diseases, namely interleukin 6 (IL-6), was achieved in the presence of many CDXs. The amino ester of L-tyrosine (X1AELT) was the most effective in reducing IL-6 production (52.2 ± 13.2%) by LPS-stimulated macrophages. Moreover, it was ≈1.2 times better than the D-enantiomer. Indeed, enantioselectivity was observed for the majority of the tested compounds. Thus, their evaluation as promising anti-inflammatory drugs should be considered.

Echinacea purpurea Fractions Represent Promising Plant-Based Anti-Inflammatory Formulations.

Echinacea purpurea is traditionally used in the treatment of inflammatory diseases. Therefore, we investigated the anti-inflammatory capacity of E. purpurea dichloromethanolic (DE) and ethanolic extracts obtained from flowers and roots (R). To identify the class of compounds responsible for the strongest bioactivity, the extracts were fractionated into phenol/carboxylic acid (F1) and alkylamide fraction (F2). The chemical fingerprint of bioactive compounds in the fractions was evaluated by LC-HRMS. E. purpurea extracts and fractions significantly reduced pro-inflammatory cytokines (interleukin 6 and/or tumor necrosis factor) and reactive oxygen and nitrogen species (ROS/RNS) production by lipopolysaccharide-stimulated primary human monocyte-derived macrophages. Dichloromethanolic extract obtained from roots (DE-R) demonstrated the strongest anti-inflammatory activity. Moreover, fractions exhibited greater anti-inflammatory activity than whole extract. Indeed, alkylamides must be the main compounds responsible for the anti-inflammatory activity of extracts; thus, the fractions presenting high content of these compounds presented greater bioactivity. It was demonstrated that alkylamides exert their anti-inflammatory activity through the downregulation of the phosphorylation of p38, ERK 1/2, STAT 3, and/or NF-κB signaling pathways, and/or downregulation of cyclooxygenase 2 expression. E. purpurea extracts and fractions, mainly DE-R-F2, are promising and powerful plant-based anti-inflammatory formulations that can be further used as a basis for the treatment of inflammatory diseases.

Base editing screens map mutations affecting interferon-γ signaling in cancer.

Interferon-γ (IFN-γ) signaling mediates host responses to infection, inflammation and anti-tumor immunity. Mutations in the IFN-γ signaling pathway cause immunological disorders, hematological malignancies, and resistance to immune checkpoint blockade (ICB) in cancer; however, the function of most clinically observed variants remains unknown. Here, we systematically investigate the genetic determinants of IFN-γ response in colorectal cancer cells using CRISPR-Cas9 screens and base editing mutagenesis. Deep mutagenesis of JAK1 with cytidine and adenine base editors, combined with pathway-wide screens, reveal loss-of-function and gain-of-function mutations, including causal variants in hematological malignancies and mutations detected in patients refractory to ICB. We functionally validate variants of uncertain significance in primary tumor organoids, where engineering missense mutations in JAK1 enhanced or reduced sensitivity to autologous tumor-reactive T cells. We identify more than 300 predicted missense mutations altering IFN-γ pathway activity, generating a valuable resource for interpreting gene variant function.

A spatially resolved atlas of the human lung characterizes a gland-associated immune niche.

Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture of lung and airways, we profiled five proximal-to-distal locations of healthy human lungs in depth using multi-omic single cell/nuclei and spatial transcriptomics (queryable at lungcellatlas.org ). Using computational data integration and analysis, we extend beyond the suspension cell paradigm and discover macro and micro-anatomical tissue compartments including previously unannotated cell types in the epithelial, vascular, stromal and nerve bundle micro-environments. We identify and implicate peribronchial fibroblasts in lung disease. Importantly, we discover and validate a survival niche for IgA plasma cells in the airway submucosal glands (SMG). We show that gland epithelial cells recruit B cells and IgA plasma cells, and promote longevity and antibody secretion locally through expression of CCL28, APRIL and IL-6. This new 'gland-associated immune niche' has implications for respiratory health.

On the Bioactivity of Echinacea purpurea Extracts to Modulate the Production of Inflammatory Mediators.

Inflammatory diseases are the focus of several clinical studies, due to limitations and serious side effects of available therapies. Plant-based drugs (e.g., salicylic acid, morphine) have become landmarks in the pharmaceutical field. Therefore, we investigated the immunomodulatory effects of flowers, leaves, and roots from Echinacea purpurea. Ethanolic (EE) and dichloromethanolic extracts (DE) were obtained using the Accelerated Solvent Extractor and aqueous extracts (AE) were prepared under stirring. Their chemical fingerprint was evaluated by liquid chromatography-high resolution mass spectrometry (LC-HRMS). The pro- and anti-inflammatory effects, as well as the reduction in intracellular reactive oxygen and nitrogen species (ROS/RNS), of the different extracts were evaluated using non-stimulated and lipopolysaccharide-stimulated macrophages. Interestingly, AE were able to stimulate macrophages to produce pro-inflammatory cytokines (tumor necrosis factor -TNF-α, interleukin -IL-1ß, and IL-6), and to generate ROS/RNS. Conversely, under an inflammatory scenario, all extracts reduced the amount of pro-inflammatory mediators. DE, alkylamides-enriched extracts, showed the strongest anti-inflammatory activity. Moreover, E. purpurea extracts demonstrated generally a more robust anti-inflammatory activity than clinically used anti-inflammatory drugs (dexamethasone, diclofenac, salicylic acid, and celecoxib). Therefore, E. purpurea extracts may be used to develop new effective therapeutic formulations for disorders in which the immune system is either overactive or impaired.

Microfluidic mixing system for precise PLGA-PEG nanoparticles size control.

In this study, a microfluidic device was employed to produce polymeric nanoparticles (NPs) with well-controlled sizes. The influence of several parameters in the synthesis process, namely, polymer concentration, flow rate and flow rate ratio between the aqueous and organic solutions was investigated. To evaluate the NPs size effect, three diameters were selected (30, 50 and 70 nm). Their cytocompatibility was demonstrated on endothelial cells and macrophages. Additionally, their efficacy to act as drug carriers was assessed in an in vitro inflammatory scenario. NPs loaded and released diclofenac (DCF) in a size-dependent profile (smaller sizes presented lower DCF content and higher release rate). Moreover, 30 nm NPs were the most effective in reducing prostaglandin E2 concentration. Therefore, this study demonstrates that microfluidics can generate stable NPs with controlled sizes, high monodispersity and enhanced batch-to-batch reproducibility. Indeed, NPs size is a crucial parameter for drug encapsulation, release and overall biological efficacy.

Stress response markers in the blood of São Tomé green sea turtles (Chelonia mydas) and their relation with accumulated metal levels.

Metals are persistent worldwide being harmful for diverse organisms and having complex and combined effects with other contaminants in the environment. Sea turtles accumulate these contaminants being considered good bioindicator species for marine pollution. However, very little is known on how this is affecting these charismatic animals. São Tomé and Príncipe archipelago harbours important green sea turtle (Chelonia mydas) nesting and feeding grounds. The main goal of this study was to determine metal and metalloid accumulation in the blood of females C. mydas nesting in São Tomé Island, and evaluate the possible impacts of this contamination by addressing molecular stress responses. Gene expression analysis was performed in blood targeting genes involved in detoxification/sequestration and metal transport (mt, mtf and fer), and in antioxidant and oxidative stress responses (cat, sod, gr, tdx, txrd, selp and gclc). Micronuclei analysis in blood was also addressed as a biomarker of genotoxicity. Present results showed significant correlations between different gene expressions with the metals evaluated. The best GLM models and significant relationships were found for mt expression, for which 78% of the variability was attributed to metal levels (Al, Cu, Fe, Hg, Pb and Zn), followed by micronuclei count (65% - Cr, Cu, Fe, Hg, Mn and Zn), tdx expression (52% - Cd, Fe, Mn, Pb and Se), and cat expression (52% - As, Fe, Se and Cd x Hg). Overall, this study demonstrates that these green sea turtles are trying to adapt to the oxidative stress and damage produced by metals through the increased expression of antioxidants and other protectors, which raises concerns about the impacts on these endangered organisms' fitness. Furthermore, promising biomarker candidates associated to metal stress were identified in this species that may be used in future biomonitoring studies using C. mydas' blood, allowing for a temporal follow-up of the organisms.

Cells of the human intestinal tract mapped across space and time.

The cellular landscape of the human intestinal tract is dynamic throughout life, developing in utero and changing in response to functional requirements and environmental exposures. Here, to comprehensively map cell lineages, we use single-cell RNA sequencing and antigen receptor analysis of almost half a million cells from up to 5 anatomical regions in the developing and up to 11 distinct anatomical regions in the healthy paediatric and adult human gut. This reveals the existence of transcriptionally distinct BEST4 epithelial cells throughout the human intestinal tract. Furthermore, we implicate IgG sensing as a function of intestinal tuft cells. We describe neural cell populations in the developing enteric nervous system, and predict cell-type-specific expression of genes associated with Hirschsprung's disease. Finally, using a systems approach, we identify key cell players that drive the formation of secondary lymphoid tissue in early human development. We show that these programs are adopted in inflammatory bowel disease to recruit and retain immune cells at the site of inflammation. This catalogue of intestinal cells will provide new insights into cellular programs in development, homeostasis and disease.

Fishroesomes as carriers with antioxidant and anti-inflammatory bioactivities.

The great diversity of marine habitats and organisms renders them a high-value source to find/develop novel drugs and formulations. Therefore, herein, sardine (Sardina pilchardus) roe was used as a lipidic source to produce liposomes. This fish product presents high nutritional value, being its lipidic content associated with important health benefits. Consequently, it can be advantageously used to produce therapeutically active delivery devices. Roe lipids were extracted using the Matyash method. After lipid film hydration and extrusion, sardine roe-derived large unilamellar liposomes (LUVs), designated as fishroesomes, presented a size of ≈330 nm and a significant negative surface charge (≈-27 mV). Radical scavenging assays demonstrated that fishroesomes efficiently neutralized peroxyl, hydroxyl and nitric oxide radicals. Moreover, fishroesomes significantly reduced the expression of pro-inflammatory cytokines and chemokines by LPS-stimulated macrophages at non-toxic concentrations for L929 and THP-1 cells. Consequently, the developed liposomes exhibit unique properties as bioactive drug carriers for inflammatory diseases treatment.

Werner Helicase Is a Synthetic-Lethal Vulnerability in Mismatch Repair-Deficient Colorectal Cancer Refractory to Targeted Therapies, Chemotherapy, and Immunotherapy.

Targeted therapies, chemotherapy, and immunotherapy are used to treat patients with mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer. The clinical effectiveness of targeted therapy and chemotherapy is limited by resistance and drug toxicities, and about half of patients receiving immunotherapy have disease that is refractory to immune checkpoint inhibitors. Loss of Werner syndrome ATP-dependent helicase (WRN) is a synthetic lethality in dMMR/MSI-H cells. To inform the development of WRN as a therapeutic target, we performed WRN knockout or knockdown in 60 heterogeneous dMMR colorectal cancer preclinical models, demonstrating that WRN dependency is an almost universal feature and a robust marker for patient selection. Furthermore, models of resistance to clinically relevant targeted therapy, chemotherapy, and immunotherapy retain WRN dependency. These data show the potential of therapeutically targeting WRN in patients with dMMR/MSI-H colorectal cancer and support WRN as a therapeutic option for patients with dMMR/MSI-H cancers refractory to current treatment strategies. SIGNIFICANCE: We found that a large, diverse set of dMMR/MSI-H colorectal cancer preclinical models, including models of treatment-refractory disease, are WRN-dependent. Our results support WRN as a promising synthetic-lethal target in dMMR/MSI-H colorectal cancer tumors as a monotherapy or in combination with targeted agents, chemotherapy, or immunotherapy.This article is highlighted in the In This Issue feature, p. 1861.

Structural and elemental analysis of biochars in the search of a synthetic path to mimetize anthropic Amazon soils.

In this work, chemical and structural properties of various biochars were analyzed and compared with those from a highly stable anthropic soil, Terra Preta de Índio (TPI). TPI is believed to be responsible for the fertility of Amazonian soils and their stability; therefore, the production of a synthetic TPI would be of great interest for agricultural applications. Biochar produced from different raw biomasses were comprehensively characterized and, based on the obtained results, a preliminary study was performed testing three different routes of chemical activation using nitric acid, phosphoric acid, and potassium hydroxide as activating agents. After chemical activations, metal contents in the biochars decreased, as expected, and high degrees of carbonization were observed. In the case of the activation performed with HNO3, intense signals related to carboxylic groups in TG-MS analysis and in potentiometric titrations point out to a highly oxygenated biochar. Structural analysis showed that activations generated point defects in sp2-carbon structures of biochar, with the material obtained after KOH activation showing a high surface area (569 m2 g-1), an important feature for the use as soil amendment.

Encapsulation of essential oils using cinnamic acid grafted chitosan nanogel: Preparation, characterization and antifungal activity.

Chemical modifications in the chitosan structure may result in obtaining a new material with improved chemical properties, such as an ability to encapsulate lipophilic compounds. This study aimed to synthesize cinnamic acid grafted chitosan nanogel to encapsulate the essential oils of Syzygium aromaticum and Cinnamomum ssp., in order to develop a material to be applied in the control of dermatophytosis caused by the fungus Microsporum canis. The cinnamic acid graft in chitosan was verified by the Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), Solid State Nuclear Magnetic Resonance of the 13C Nucleus (13C SSNMR) and Thermal analysis coupled to mass spectrometry (TG-MS) techniques. The nanogel obtained showed affinity for the essential oils of S. aromaticum and Cinnamomum, with encapsulation efficiencies equal to 74% and 89%, respectively. When in an aqueous medium the nanogel with the encapsulated essential oils was able to form stable nanoparticles with average sizes of 176.0 ± 54.3 nm and 263.0 ± 81.4 nm. The cinnamic acid grafted chitosan nanogel showed antifungal activity in vitro against M. canis, inhibiting up to 53.96% of its mycelial growth. Complete inhibition of mycelial growth was achieved by the nanogel with encapsulated essential oils. The results found in this work demonstrated the development of a material with potential application in the control of dermatophytosis caused by the fungus M. canis.

Antioxidant and Anti-Inflammatory Activities of Cytocompatible Salvia officinalis Extracts: A Comparison between Traditional and Soxhlet Extraction.

Chronic inflammation is characterized by an overproduction of several inflammatory mediators (e.g., reactive species and interleukins -IL) that play a central role in numerous diseases. The available therapies are often associated with serious side effects and, consequently, the need for safer drugs is of utmost importance. A plant traditionally used in the treatment of inflammatory conditions is Salvia officinalis. Therefore, conventional maceration and infusion of its leaves were performed to obtain hydroethanolic (HE-T) and aqueous extracts (AE-T), respectively. Their efficacy was compared to soxhlet extracts, namely aqueous (AE-S), hydroethanolic (HE-S), and ethanolic extracts (EE-S). Thin-layer chromatography demonstrated the presence of rosmarinic acid, carnosol, and/or carnosic acid in the different extracts. Generally, soxhlet provided extracts with higher antioxidant activities than traditional extraction. Moreover, under an inflammatory scenario, EE-S were the most effective, followed by HE-S, HE-T, AE-T, and AE-S, in the reduction of IL-6 and TNF-α production. Interestingly, the extracts presented higher or similar anti-inflammatory activity than diclofenac, salicylic acid, and celecoxib. In conclusion, the extraction method and the solvents of extraction influenced the antioxidant activity, but mainly the anti-inflammatory activity of the extracts. Therefore, this natural resource can enable the development of effective treatments for oxidative stress and inflammatory diseases.

Yicathins B and C and Analogues: Total Synthesis, Lipophilicity and Biological Activities.

Natural products have always been an important source of new hits and leads in drug discovery, with the marine environment being regarded as a significant source of novel and exquisite bioactive compounds. Yicathins B and C are two marine-derived xanthones that have shown antibacterial and antifungal activity. Herein, the total synthesis of these yicathins and six novel analogues is reported for the first time. As marine natural products tend to have very lipophilic scaffolds, the lipophilicity of yicathins and their analogues was evaluated in the classical octanol/water system and a biomimetic model-based system. As the xanthonic nucleus is a "privileged structure", other biological activities were evaluated, namely antitumor and anti-inflammatory activities. An interesting anti-inflammatory activity was identified for yicathin analogues that paves the way for the design of dual activity (anti-infective and anti-inflammatory) marine-inspired xanthone derivatives.

Permanently hydrophilic, piezoelectric PVDF nanofibrous scaffolds promoting unaided electromechanical stimulation on osteoblasts.

Biomimetic functional scaffolds for tissue engineering should fulfil specific requirements concerning structural, bio-chemical and electro-mechanical characteristics, depending on the tissue that they are designed to resemble. In bone tissue engineering, piezoelectric materials based on poly(vinylidene fluoride) (PVDF) are on the forefront, due to their inherent ability to generate surface charges under minor mechanical deformations. Nevertheless, PVDF's high hydrophobicity hinders sufficient cell attachment and expansion, which are essential in building biomimetic scaffolds. In this study, PVDF nanofibrous scaffolds were fabricated by electrospinning to achieve high piezoelectricity, which was compared with drop-cast membranes, as it was confirmed by XRD and FTIR measurements. Oxygen plasma treatment of the PVDF surface rendered it hydrophilic, and surface characterization revealed a long-term stability. XPS analysis and contact angle measurements confirmed an unparalleled two-year stability of hydrophilicity. Osteoblast cell culture on the permanently hydrophilic PVDF scaffolds demonstrated better cell spreading over the non-treated ones, as well as integration into the scaffold as indicated by SEM cross-sections. Intracellular calcium imaging confirmed a higher cell activation on the piezoelectric electrospun nanofibrous scaffolds. Combining these findings, and taking advantage of the self-stimulation of the cells due to their attachment on the piezoelectric PVDF nanofibers, a 3D tissue-like functional self-sustainable scaffold for bone tissue engineering was fabricated.