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The Module-0 Demonstrator is a single-phase 600 kg liquid argon time projection chamber operated as a prototype for the DUNE liquid argon near detector. Based on the ArgonCube design concept, Module-0 features a novel 80k-channel pixelated charge readout and advanced high-coverage photon detection system. In this paper, we present an analysis of an eight-day data set consisting of 25 million cosmic ray events collected in the spring of 2021. We use this sample to demonstrate the imaging performance of the charge and light readout systems as well as the signal correlations between the two. We also report argon purity and detector uniformity measurements and provide comparisons to detector simulations.

The Deep Underground Neutrino Experiment (DUNE) is an international, world-class experiment aimed at exploring fundamental questions about the universe that are at the forefront of astrophysics and particle physics research. DUNE will study questions pertaining to the preponderance of matter over antimatter in the early universe, the dynamics of supernovae, the subtleties of neutrino interaction physics, and a number of beyond the Standard Model topics accessible in a powerful neutrino beam. A critical component of the DUNE physics program involves the study of changes in a powerful beam of neutrinos, i.e., neutrino oscillations, as the neutrinos propagate a long distance. The experiment consists of a near detector, sited close to the source of the beam, and a far detector, sited along the beam at a large distance. This document, the DUNE Near Detector Conceptual Design Report (CDR), describes the design of the DUNE near detector and the science program that drives the design and technology choices. The goals and requirements underlying the design, along with projected performance are given. It serves as a starting point for a more detailed design that will be described in future documents.

Helichrysum italicum (immortelle) essential oil is one of the most popular essential oils worldwide and it has many beneficial properties, including antimicrobial. However, in this plant, the chemical diversity of the essential oil is very pronounced. The aim of this work was to process the GC-MS results of four samples of H. italicum essential oil of Serbian origin by chemometric tools, and evaluate the antimicrobial activity in vitro and in silico. Overall, 47 compounds were identified, the most abundant were γ-curcumene, α-pinene, and ar-curcumene, followed by α-ylangene, neryl acetate, trans-caryophyllene, italicene, α-selinene, limonene, and italidiones. Although the four samples of H. italicum essential oil used in this study were obtained from different producers in Serbia, they belong to the type of essential oil rich in sesquiterpenes (γ-curcumene and ar-curcumene chemotype). In vitro antimicrobial potential showed that five were sensitive among ten strains of tested microorganisms: Staphylococcus aureus, Listeria monocytogenes, Bacillus cereus, Saccharomyces cerevisiae, and Candida albicans. Therefore, these microorganism models were used further for in silico molecular docking through the mechanism of ATP-ase inhibitory activity. Results showed that among all compounds from H. italicum essential oil, neryl acetate has the highest predicted binding energy. Artificial neural network modeling (ANN) showed that two major compounds γ-curcumene and α-pinene, as well as minor compounds such as trans-β-ocimene, terpinolene, terpinene-4-ol, isoitalicene, italicene, cis-α-bergamotene, trans-α-bergamotene, italidiones, trans-β-farnesene, γ-selinene, β-selinene, α-selinene, and guaiol are responsible for the antimicrobial activity of H. italicum essential oil. The results of this study indicate that H. italicum essential oil samples rich in γ-curcumene, α-pinene, and ar-curcumene cultivated in Serbia (Balkan) have antimicrobial potential both in vitro and in silico. In addition, according to ANN modeling, the proportion of neryl acetate and other compounds detected in these samples has the potential to exhibit antimicrobial activity.

Efforts are being made globally to improve the evaluation and understanding of endocrine-disrupting chemicals. Recognition of their impact on human health and the environment has stimulated attention and research in this field. Various stakeholders, including scientists, regulatory agencies, policymakers, and industry representatives, are collaborating to develop robust methodologies and guidelines for assessing these disruptors. A key aspect of these efforts is the development of standardized testing protocols and guidelines that aim to provide consistent and reliable methods for identifying and characterizing endocrine disruptors. When evaluating the potential endocrine-disrupting activity of chemicals, no single test is capable of detecting all relevant endocrine-disrupting agents. The test battery approach is designed to reduce the risk of false negative results for compounds with toxic potential. A weight-of-evidence approach is therefore necessary for endocrine disruptor evaluation. This approach considers various types of data from multiple sources, assessing the overall strength, consistency, and reliability of the evidence. OECD guidelines are highly regarded for their scientific rigor, transparency, and consensus-based development process. It is crucial to explore and develop new methodologies that can effectively evaluate the risks associated with potential endocrine disruptors. Integrating these methods into a comprehensive weight-of-evidence framework will enhance risk assessments and facilitate informed decisions regarding the regulation and management of these substances, ensuring the protection of human health and the environment from their adverse effects.

Pregnant women may use EOs in case of morning sickness, nausea, stress management, etc. Little is known about the potential danger that EOs represent for the placenta and therefore for the pregnancy. Our aim was to explore and compare the placental toxicity and potential endocrine disrupting effects of niaouli, orange, tea tree, wintergreen and ylang-ylang EOs, and their key compounds: 4-terpineol, 1,8-cineol, limonene, methyl salicylate and benzyl salicylate. We studied the release of four hormones and the activation of P2X7 receptor in JEG-Tox human placental cells as key biomarkers for endocrine toxicity. We observed that niaouli, orange, tea tree, wintergreen and ylang-ylang EOs and their key components disrupted at least one of the studied hormones but none of them activated the P2X7 cell death receptor. The tested EOs appear then to be more hormonal modulators rather than EDCs in human placental cells. The hormonal effects observed with the key components were very different from those observed with the EOs. EOs are very complex mixtures, and it is essential to study whole EOs rather than their components individually in safety assessment.

St. John’s wort (Hypericum perforatum, Hypericaceae) has long been used in traditional medicine as a potent remedy, while many other species of this genus have not been thoroughly investigated. The study aimed to detect the biological activity, including antioxidant, antihyperglycemic, anticholinergic, antimicrobial and monoaminoxidase inhibitory potential, of water-alcoholic extracts of three species autochthonous for Serbia and Greece from plant genus Hypericum (section Hypericum—H. tetrapterum, H. maculatum ssp. immaculatum and H. triquetrifolium), followed by phytochemical profiling. The highest amount of phenolics was recorded in H. maculatum subsp. immaculatum extract, while the highest abundance of flavonoids was characteristic of H. tetrapterum extract. Hypericin and hyperforin, quercetin, and its flavonoid, rutin, were present in all of the evaluated species. The evaluated species were good scavengers of DPPH, OH and NO radicals, as well as potent reducers of ferric ions in FRAP assay. Furthermore, the evaluated species were shown as potent inhibitors of monoaminoxidase A and α-glucosidase and modest inhibitors of acetylcholinesterase, monoaminoxidase B and α-amylase. No anti-Candida activity was recorded, but the extracts were effective against MRSA Staphylococcus aureus and Enterococcus sp., as well as against Proteus mirabilis. The obtained results strongly highlight the need for further in vivo studies in order to better define the potential of the medicinal application of the studied species.

Ironwort (Sideritis montana L.), mountain germander (Teucrium montanum L.), wall germander (Teucrium chamaedrys L.), and horehound (Marrubium peregrinum L.) are species widely distributed across Europe and are also found in North Africa and West Asia. Because of their wide distribution they express significant chemical diversity. For generations, these plants have been used as medical herbs for treating different aliments. The aim of this paper is to analyze volatile compounds of four selected species that belong to the subfamily Lamioideae, family Lamiaceae, and inspect scientifically proven biological activities and potential uses in modern phytotherapy in relation to traditional medicine. Therefore, in this research, we analyze the volatile compounds from this plants, obtained in laboratory by a Clevenger-type apparatus, followed by liquid–liquid extraction with hexane as the solvent. The identification of volatile compounds is conducted by GC-FID and GC-MS. Although these plants are poor in essential oil, the most abundant class of volatile components are mainly sesquiterpenes: germacrene D (22.6%) in ironwort, 7-epi-trans-sesquisabinene hydrate (15.8%) in mountain germander, germacrene D (31.8%) and trans-caryophyllene (19.7%) in wall germander, and trans-caryophyllene (32.4%) and trans-thujone (25.1%) in horehound. Furthermore, many studies show that, in addition to the essential oil, these plants contain phenols, flavonoids, diterpenes and diterpenoids, iridoids and their glycosides, coumarins, terpenes, and sterols, among other active compounds, which affect biological activities. The other goal of this study is to review the literature that describes the traditional use of these plants in folk medicine in regions where they grow spontaneously and compare them with scientifically confirmed activities. Therefore, a bibliographic search is conducted on Science Direct, PubMed, and Google Scholar to gather information related to the topic and recommend potential applications in modern phytotherapy. In conclusion, we can say that selected plants could be used as natural agents for promoting health, as a source of raw material in the food industry, and as supplements, as well as in the pharmaceutical industry for developing plant-based remedies for prevention and treatment of many diseases, especially cancer.

Gastrointestinal problems are among the most common health problems which can acutely affect the healthy population and chronically involve health risks, seriously affecting the quality of life. Identifying the risk of gastrointestinal diseases in the early phase by indirect methods can increase the healing rate and the quality of life.: The proposal of this study is to verify a correlation between gastrointestinal and periodontal problems and the risk of inflammatory gastrointestinal diseases (IBD). The study was conducted on 123 people who were observed to have gastrointestinal and psychological problems. The participants were divided into three groups, depending on each one’s diagnosis. The control group (CG) was composed of 37 people who did not fit either irritable bowel syndrome (IBS) according to the ROME IV criteria, nor were inflammatory markers positive for IBD. Group 2 (IBS) was composed of 44 participants diagnosed with IBS according to the ROME IV criteria. Group 3 was composed of 42 participants who were diagnosed with IBD. All study participants underwent anthropometric, micro-Ident, and quality of life tests. A directly proportional relationship of the presence of bacteria with IBD patients with the exception of Capnocytophaga spp. and Actinobacillus actinomycetemcomitans was observed. These two bacteria correlated significantly with IBS. Follow-up of the study participants will help determine whether periodontal disease can be used as an indicator of severe colorectal disease. In addition, this study should be continued especially in the case of IBD more thoroughly to follow and reduce the risk of malignancy.

The introduction of fifth generation mobile networks is underway all over the world which makes many people think about the security of the network from any hacking. Over the past few years, researchers from around the world have raised this issue intensively as new technologies seek to integrate into many areas of business and human infrastructure. This paper proposes to implement an IDS (Intrusion Detection System) machine learning approach into the 5G core architecture to serve as part of the security architecture. This paper gives a brief overview of intrusion detection datasets and compares machine learning and deep learning algorithms for intrusion detection. The models are built on the basis of two network data CICIDS2017 and CSE-CIC-IDS-2018. After testing, the ML and DL models are compared to find the best fit with a high level of accuracy. Gradient Boost emerged as the top method when we compared the best results based on metrics, displaying 99.3% for a secure dataset and 96.4% for attacks on the test set.

Garden angelica (Angelica archangelica L.), native to the northern temperate region, is widespread in Europe and Asia. Since the middle ages, it has been used for healing and as a vegetable in traditional dishes. In the modern era, it has been proven that A. archangelica has a complex chemical composition. The main derivatives that contribute to the plant’s biological activities are essential oil and coumarins. In this review, the focus is on the cross-analysis of the taxonomy of A. archangelica, and its distribution in different regions, with the presentation of the richness of its biochemical composition, which overall contributes to the widespread use of the roots of this plant in folk medicine. It belongs to the plants that were introduced to the wider area of Central, Eastern, and Southern Europe; as a medicinal plant, it represents a significant part of the medical flora of many areas. Cluster analysis of pooled data indicates a clear differentiation of chemotypes.

Forskolin, used in folk medicine since ancient times, is now available as a dietary supplement, with an indication as a fat burner and appetite suppressant. However, the safety of forskolin is poorly documented especially for pregnant women. The question that we raised is what about the safety of forskolin in pregnant women? As the placenta, an endocrine organ, is the key organ of pregnancy, we evaluated the in vitro placental toxicity of forskolin. We focused first on the activation of a P2X7 degenerative receptor as a key biomarker for placental toxicity, and second on steroid and peptide hormonal secretion. We observed that forskolin activated P2X7 receptors and disturbed estradiol, progesterone, hPL and hyperglycosylated hCG secretion in human placental JEG-Tox cells. To the best of our knowledge, we highlighted, for the first time, that forskolin induced endocrine disturbance in placental cells. Forskolin does not appear to be a safe product for pregnant women and restrictions should be taken.

Background and objectives: Irritable bowel syndrome (IBS) does not only have a complex pathophysiological evolution with central and peripheral mechanisms. This study aimed to monitor the neuropsychiatric part of IBS and its management, following the quality of life of patients with IBS. Materials and Methods: Participants numbering 145 were investigated in this study for 6 months and were divided into four groups, namely the control group with a symptomatic period of less than 6 months (n = 34), the group with irritable bowel syndrome (IBS; n = 58), IBS and neuropsychiatric treatment (n = 32), and IBS with probiotic treatment (n = 22). Clinical and paraclinical analyses as well as quality of life were monitored by domestic and international psychological questionnaires. Results: It was observed that, in patients with pro-longed symptoms, neuropsychiatric impairment occurred more frequently, and both clinical and paraclinical analyses improved significantly (p < 0.05) more so in those with complex allopathic treatment and in those with probiotic treatment. There were no significant differences between the two research groups. Conclusions: It has been shown that the neuropsychological component of IBS plays an important role in its treatment, and modern probation therapy can achieve similar results to those of neuropsychiatry. This also requires further studies to ensure the best combination in the approach to IBS.

In pregnant women, the lungs, skin and placenta are exposed daily to endocrine-disrupting chemicals (EDCs). EDCs induce multiple adverse effects, not only on endocrine organs, but also on non-endocrine organs, with the P2X7 cell death receptor being potentially the common key element. Our objective was first to investigate mechanisms of EDCs toxicity in both endocrine and non-endocrine cells through P2X7 receptor activation, and second, to compare the level of activation in lung, skin and placental cells. In addition, apoptosis in placental cells was studied because the placenta is the most exposed organ to EDCs and has essential endocrine functions. A total of nine EDCs were evaluated on three human cell models. We observed that the P2X7 receptor was not activated by EDCs in lung non-endocrine cells but was activated in skin and placenta cells, with the highest activation in placenta cells. P2X7 receptor activation and apoptosis are pathways shared by all tested EDCs in endocrine placental cells. P2X7 receptor activation along with apoptosis induction could be key elements in understanding endocrine placental and skin disorders induced by EDCs.

Unlike other studies that only determined the chemical composition of essential oils depending on their geographic origin, this research investigated the effect of weather conditions (temperature, precipitation, and insolation) on the chemical composition of Nepeta nuda L. essential oil. The collection of wild-growing N. nuda was carried out during three successive years, 2019, 2020, and 2021 at Rtanj Mountain (Serbia) on the same date (July 7th). Essential oil extraction from the plant was performed by hydro-distillation. After gas chromatographic-mass spectrometric analysis, a total of 102 volatile compounds were separated from N. nuda, during the observed period, 28 were unidentified, compromising between 5.0% and 8.7%, depending on the year. A multiple linear regression model was created, and statistical analyses were performed to provide knowledge about the prediction, feature profile, and the similarity in contents of active compounds of the N. nuda essential oil. The influence of temperature on the accumulation of the most abundant component, 1,8-cineole, was positive, while the impact of precipitation and insolation was negative. According to the cluster tree, there are four chemotypes of N. nuda essential oil: with nepetalactone, 1,8-cineole, mixed (nepetalactone+1,8-cineole+germacrene D), and nonspecific chemotypes. Bearing in mind that the biological activity of a raw material depends on the chemotype and environmental factors, this is a topic that deserves a more detailed approach. The N. nuda and its essential oil are promising materials with high biological potential, and these deserve further detailed investigation.

The COVID-19 pandemic has had a major impact on cardiovascular emergencies. The aim of this study was to investigate the impact of the COVID-19 pandemic on a regional network for management of ST-segment elevation acute myocardial infarction (STEMI). Methods: We report a single center’s experience of patients hospitalized for ACS in a high-volume hub of a STEMI network during the lockdown (in the first pandemic trimester), compared with the same time interval of the previous year and including all consecutive patients referred for an AMI during the second trimester of 2020 (from April to June) or during the same time interval of the previous year, 2019. Results: The absolute number of hospital admissions for AMI decreased by 22.3%, while the non-AMI hospitalizations decreased by 77.14% in Q2-2020 compared to Q2-2019 (210 vs. 48, p < 0.0001). As a consequence, the percentage of AMI cases from the total number of hospital admission increased from 38% to 68% (p < 0.0001), AMI becoming the dominant pathology. In the STEMI group there was a significant reduction of 55% in the absolute number of late STEMI presentations. Functionality of the STEMI network at the hub level did not present a significant alteration with only a minor increase in the door-to-balloon time, from 34 min to 41 min. However, at the level of the network we recorded a lower number of critical cases transferred to the interventional center, with a dramatic reduction of 56.1% in the number of critical STEMI cases arriving in the acute cardiac care unit (17.0% vs. 7.3%, p-0.04 for KILLIP class III, and 21.17% vs. 11.11%, p = 0.08 for resuscitated out of hospital cardiac arrest). Conclusions: The COVID-19 outbreak did not have a major impact on the interventional center’s functionality, but it limited the capacity of the regional STEMI network to bring the critical patient with complicated STEMI to the cathlab in time during the first months of the lockdown. Even a very well-functioning STEMI network like the one in Central Romania had difficulties bringing the most critical STEMI cases to the cathlab in time.

Cardiac complications are among the most frequent extrapulmonary manifestations of COVID-19 and are associated with high mortality rates. Moreover, positive SARS-CoV-2 patients with underlying cardiovascular disease are more likely to require intensive care and are at higher risk of death. The underlying mechanism for myocardial injury is multifaceted, in which the severe inflammatory response causes myocardial inflammation, coronary plaque destabilization, acute thrombotic events, and ischemia. Cardiac magnetic resonance (CMR) imaging is the non-invasive method of choice for identifying myocardial injury, and it is able to differentiate between underlying causes in various and often challenging clinical scenarios. Multimodal imaging protocols that incorporate CMR and computed tomography provide a complex evaluation for both respiratory and cardiovascular complications of SARS-CoV2 infection. This, in relation to biological evaluation of systemic inflammation, can guide appropriate therapeutic management in every stage of the disease. The use of artificial intelligence can further improve the diagnostic accuracy of these imaging techniques, thus enabling risk stratification and evaluation of prognosis. The present manuscript aims to review the current knowledge on the possible modalities for imaging COVID-related myocardial inflammation or post-COVID coronary inflammation and atherosclerosis.

Background: Bisphenol A (BPA), a reprotoxic and endocrine-disrupting chemical, has been substituted by alternative bisphenols such as bisphenol F (BPF) and bisphenol S (BPS) in the plastic industry. Despite their detection in placenta and amniotic fluids, the effects of bisphenols on human placental cells have not been characterized. Our objective was to explore in vitro and to compare the toxicity of BPA to its substitutes BPF and BPS to highlight their potential risks for placenta and then pregnancy. Methods: Human placenta cells (JEG-Tox cells) were incubated with BPA, BPF, and BPS for 72 h. Cell viability, cell death, and degenerative P2X7 receptor and caspases activation, and chromatin condensation were assessed using microplate cytometry and fluorescence microscopy. Results: Incubation with BPA, BPF, or BPS was associated with P2X7 receptor activation and chromatin condensation. BPA and BPF induced more caspase-1, caspase-9, and caspase-3 activation than BPS. Only BPF enhanced caspase-8 activity. Conclusions: BPA, BPF, and BPS are all toxic to human placental cells, with the P2X7 receptor being a common key element. BPA substitution by BPF and BPS does not appear to be a safe alternative for human health, particularly for pregnant women and their fetuses.

Phlorotannins are polyphenols occurring exclusively in some species of brown algae, known for numerous biological activities, e.g., antioxidant, antiproliferative, antidiabetic, and antiallergic properties. Their effects on the response of human lung cells to benzo[a]pyrene (B[a]P) has not been characterized. Our objective was to in vitro evaluate the effects of a phlorotannin-rich extract obtained from the brown algae Ascophyllum nodosum and Fucus vesiculosus on B[a]P cytotoxic effects. The A549 cell line was incubated with B[a]P for 48 and 72 h in the presence or absence of the brown algae extract. Cytochrome P450 activity, activation of P2X7 receptor, F-actin disorganization, and loss of E-cadherin expression were assessed using microplate cytometry and fluorescence microscopy. Relative to control, incubation with the brown algae extract was associated with lower B[a]P-induced CYP1 activity, lower P2X7 receptor activation, and lower reactive oxygen species production. The brown algae extract inhibited the alterations of F-actin arrangement and the downregulation of E-cadherin expression. We identified a phlorotannins-rich extract that could be deeper investigated as a cancer chemopreventive agent to block B[a]P-mediated carcinogenesis.

The morphogenesis of Hepatitis B Virus (HBV) viral particles is nucleated by the oligomerization of HBc protein molecules, resulting in the formation of an icosahedral capsid shell containing the replication-competent nucleoprotein complex made of the viral polymerase and the pre-genomic RNA (pgRNA). HBc is a phospho-protein containing two distinct domains acting together throughout the viral replication cycle. The N-terminal domain, (residues 1–140), shown to self-assemble, is linked by a short flexible domain to the basic C-terminal domain (residues 150–183) that interacts with nucleic acids (NAs). In addition, the C-terminal domain contains a series of phospho-acceptor residues that undergo partial phosphorylation and de-phosphorylation during virus replication. This highly dynamic process governs the homeostatic charge that is essential for capsid stability, pgRNA packaging and to expose the C-terminal domain at the surface of the particles for cell trafficking. In this review, we discuss the roles of the N-terminal and C-terminal domains of HBc protein during HBV morphogenesis, focusing on how the C-terminal domain phosphorylation dynamics regulate its interaction with nucleic acids throughout the assembly and maturation of HBV particles.

The aim of the study was to develop a semi-automated, computer-aided imaging technique to quantify the amount and distribution of perivascular fat at the level of the iliac arteries (periiliac adipose tissue—PIAT), and to investigate the association of this new computer-aided imaging biomarker with other biomedical imaging biomarkers, which characterize the pelvic adipose tissue (SAT—subcutaneous adipose tissue; VAT—visceral adipose tissue). We included 34 patients with peripheral arterial disease, in whom the volumes of PIAT, SAT and VAT were quantified using a dedicated software, at the level of right and left iliac arteries. Median value of PIAT was five milliliters. Patients with PIAT > five milliliters were in more advanced Fontaine classes, with more complex arterial lesions, compared to those with low PIAT (p < 0.0001). PIAT volumes presented a gradual increase with the Trans-Atlantic Inter-Society Consensus (TASC) class (2.57 +/− 1.98 in TASC A, 4.65 +/− 1.63 in TASC B, 8.79 +/− 1.99 in TASC C and 13.77 +/− 2.74 in TASC D). The distribution of PIAT between the left and right iliac axis was quasi-uniform (correlation between right and left PIAT: r = 0.46, p = 0.005). Linear regression analysis showed that the mean PIAT volume was correlated with VAT (r = 0.38, p = 0.02), but not with the SAT at the level of iliac artery origin (r = 0.16, p = 0.34). PIAT may represent a novel biomedical imaging derived biomarker, which characterizes the distribution of adipose tissue in the pelvic area and may serve as an indicator of the severity and complexity of lower limb ischemia.

Mydriasis is required prior to many eye examinations and ophthalmic surgeries. Nowadays, phenylephrine hydrochloride (PHE) and tropicamide (TPC) are extensively used to induce mydriasis. Several pharmaceutic dosage forms of these two active ingredients have been described. However, no optimal therapeutic strategy has reached the market. The present work focuses on the formulation and evaluation of a mucoadhesive ion-activated in situ gelling delivery system based on gellan gum and hydroxyethylcellulose (HEC) for the delivery of phenylephrine and tropicamide. First, in vitro drug release was studied to assess appropriate sustained drug delivery on the ocular surface region. Drug release mechanisms were explored and explained using mathematical modeling. Then, in situ gelling delivery systems were visualized using scanning electron microscopy illustrating the drug release phenomena involved. Afterward, cytotoxicity of the developed formulations was studied and compared with those of commercially available eye drops. Human epithelial corneal cells were used. Finally, mydriasis intensity and kinetic was investigated in vivo. Mydriasis pharmacodynamics was studied by non-invasive optical imaging on vigilant rabbits, allowing eye blinking and nasolacrimal drainage to occur physiologically. In situ gelling delivery systems mydriasis profiles exhibited a significant increase of intensity and duration compared with those of conventional eye drops. Efficient mydriasis was achieved following the administration of a single drop of in situ gel reducing the required amount of administered active ingredients by four- to eight-fold compared with classic eye drop regimen.

This paper reports the isolation and structural characterization of four new ent-kaurane derivatives from the Lamiaceae plant Sideritis hyssopifolia. Planar structures and relative configurations were determined using both mass spectrometry and nuclear magnetic resonance (1D and 2D). Absolute configurations were determined by comparing experimental and theoretical electronic circular dichroism spectra. The cytotoxic and microbial activities of all new compounds were tested. Compounds that were non-cytotoxic were further evaluated for anti-inflammatory activity.

We report the case of a patient with a pelvic abscess and a malignant pancreatic tumor. The management of this complicated diverticulitis included radiological drainage and surgery. This abscess was due to a peritoneal carcinomatosis originating from the pancreas, which is an extremely rare cause of intestinal perforation.

Efforts are being made globally to improve the evaluation and understanding of endocrine-disrupting chemicals. Recognition of their impact on human health and the environment has stimulated attention and research in this field. Various stakeholders, including scientists, regulatory agencies, policymakers, and industry representatives, are collaborating to develop robust methodologies and guidelines for assessing these disruptors. A key aspect of these efforts is the development of standardized testing protocols and guidelines that aim to provide consistent and reliable methods for identifying and characterizing endocrine disruptors. When evaluating the potential endocrine-disrupting activity of chemicals, no single test is capable of detecting all relevant endocrine-disrupting agents. The test battery approach is designed to reduce the risk of false negative results for compounds with toxic potential. A weight-of-evidence approach is therefore necessary for endocrine disruptor evaluation. This approach considers various types of data from multiple sources, assessing the overall strength, consistency, and reliability of the evidence. OECD guidelines are highly regarded for their scientific rigor, transparency, and consensus-based development process. It is crucial to explore and develop new methodologies that can effectively evaluate the risks associated with potential endocrine disruptors. Integrating these methods into a comprehensive weight-of-evidence framework will enhance risk assessments and facilitate informed decisions regarding the regulation and management of these substances, ensuring the protection of human health and the environment from their adverse effects.

Forskolin, used in folk medicine since ancient times, is now available as a dietary supplement, with an indication as a fat burner and appetite suppressant. However, the safety of forskolin is poorly documented especially for pregnant women. The question that we raised is what about the safety of forskolin in pregnant women? As the placenta, an endocrine organ, is the key organ of pregnancy, we evaluated the in vitro placental toxicity of forskolin. We focused first on the activation of a P2X7 degenerative receptor as a key biomarker for placental toxicity, and second on steroid and peptide hormonal secretion. We observed that forskolin activated P2X7 receptors and disturbed estradiol, progesterone, hPL and hyperglycosylated hCG secretion in human placental JEG-Tox cells. To the best of our knowledge, we highlighted, for the first time, that forskolin induced endocrine disturbance in placental cells. Forskolin does not appear to be a safe product for pregnant women and restrictions should be taken.

Background: Bisphenol A (BPA), a reprotoxic and endocrine-disrupting chemical, has been substituted by alternative bisphenols such as bisphenol F (BPF) and bisphenol S (BPS) in the plastic industry. Despite their detection in placenta and amniotic fluids, the effects of bisphenols on human placental cells have not been characterized. Our objective was to explore in vitro and to compare the toxicity of BPA to its substitutes BPF and BPS to highlight their potential risks for placenta and then pregnancy., Methods: Human placenta cells (JEG-Tox cells) were incubated with BPA, BPF, and BPS for 72 h. Cell viability, cell death, and degenerative P2X7 receptor and caspases activation, and chromatin condensation were assessed using microplate cytometry and fluorescence microscopy., Results: Incubation with BPA, BPF, or BPS was associated with P2X7 receptor activation and chromatin condensation. BPA and BPF induced more caspase-1, caspase-9, and caspase-3 activation than BPS. Only BPF enhanced caspase-8 activity., Conclusions: BPA, BPF, and BPS are all toxic to human placental cells, with the P2X7 receptor being a common key element. BPA substitution by BPF and BPS does not appear to be a safe alternative for human health, particularly for pregnant women and their fetuses.

The P2X7 receptor is expressed in both anterior and posterior segments of the eyeball. In the ocular surface, the P2X7 receptor is activated in case of external aggressions: preservatives and surfactants induce the activation of P2X7 receptors, leading to either apoptosis, inflammation, or cell proliferation. In the retina, the key endogenous actors of age-related macular degeneration, diabetic retinopathy, and glaucoma act through P2X7 receptors' activation and/or upregulation of P2X7 receptors' expression. Different therapeutic strategies aimed at the P2X7 receptor exist. P2X7 receptor antagonists, such as divalent cations and Brilliant Blue G (BBG) could be used to target either the ocular surface or the retina, as long as polyunsaturated fatty acids may exert their effects through the disruption of plasma membrane lipid rafts or saffron that reduces the response evoked by P2X7 receptor stimulation. Treatments against P2X7 receptor activation are proposed by using either eye drops or food supplements., Competing Interests: The authors declare no conflict of interest.