Methoxy Chalcone Derivatives: Promising Antimicrobial Agents Against Phytopathogens.

Chalcone (E)-1,3-diphenyl-prop-2-en-1-one and a series of 14 methoxylated derivatives have been synthesized via Claisen-Schmidt aldol condensation and characterized by FTIR, CG/MS/DIC, 1D (1H and 13C), 2D (COSY, HSQC, and HMBC) NMR, and EMAR techniques. All molecules were tested at 1 mM concentration for antifungal (Sclerotium sp., Macrophomina phaesolina and Colletotrichum gloeosporioides), antibacterial (Acidovorax citrulli two strains), and antiprotozoal (Phytomonas serpens) activities. Unmodified chalcone (CH0) and derivatives CH1, CH2, CH8 stood out in terms of antifungal activity. CH0 presented IC50 values of 47.3 µM (9.8 µg/mL) for the fungus C. gloeosporioides. In addition, fluorescence microscopy indicated that CH0 promoted loss of hyphal cell membrane integrity. The CH1 and CH2 derivatives promoted the inhibition of Sclerotium sp. with IC50 of 127.5 µM (32.9 µg/mL) and 110.4 µM (29.6 µg/mL), respectively. All molecules showed high activity against the phytoparasite P. serpens with IC50 values of 0.98, 2.40, 10.25, and 3.11 µM for the derivatives CH2, CH3, CH5 and CH14 respectively. The results demonstrated that derivatives methoxylated in both rings (CH2) as well as derivatives with a furan ring associated with the methoxy group in ring A, as well as unmodified chalcone can be promising agricultural fungicides for controlling the fungi studied.

Therapeutic applications of synthetic gene/genetic circuits: a patent review.

A significant limitation of numerous current genetic engineering therapy approaches is their limited control over the strength, timing, or cellular context of their therapeutic effect. Synthetic gene/genetic circuits are synthetic biology approaches that can control the generation, transformation, or depletion of a specific DNA, RNA, or protein and provide precise control over gene expression and cellular behavior. They can be designed to perform logical operations by carefully selecting promoters, repressors, and other genetic components. Patent search was performed in Espacenet, resulting in 38 selected patents with 15 most frequent international classifications. Patent embodiments were categorized into applications for the delivery of therapeutic molecules, treatment of infectious diseases, treatment of cancer, treatment of bleeding, and treatment of metabolic disorders. The logic gates of selected genetic circuits are described to comprehensively demonstrate their therapeutic applications. Synthetic gene circuits can be customized for precise control of therapeutic interventions, leading to personalized therapies that respond specifically to individual patient needs, enhancing treatment efficacy and minimizing side effects. They can be highly sensitive biosensors that provide real-time therapy by accurate monitoring various biomarkers or pathogens and appropriately synthesizing a therapeutic molecule. Synthetic gene circuits may also lead to the development of advanced regenerative therapies and to implantable biodevices that produce on-demand bioactive molecules. However, this technology faces challenges for commercial profitability. The genetic circuit designs need adjustments for specific applications, and may have disadvantages like toxicity from multiple regulators, homologous recombination, context dependency, resource overuse, and environmental variability.

Is tetrodotoxin intoxication the cause of "zombi voice" in Haiti?

OBJECTIVE: Zombification, a magical and religious process in Haiti, has been scientifically studied and remains relevant. Originating from the convergence of African, Caribbean, and Christian rites, it involves a comatose trance, transforming individuals into living dead through Voodoo practices. Haitian zombies consistently exhibit a preserved expression marked by a nasal voice, a result of nasalization-using nasal cavities as resonators during phonation. The aim of this study was to ascertain the mechanisms through which zombification could impact the voices of the subjects. METHODS: A comprehensive investigation was conducted using both primary and secondary sources. Primary sources involved direct or reported testimonies of individuals undergoing zombification, with audio or video recordings available from the collections of the Laboratory of Anthropology, Archaeology, and Biology (UVSQ/Paris-Saclay University), as well as on the internet. Secondary sources encompassed the entirety of existing literature regarding zombification in Haiti on one hand, alterations in the voices of subjects when mentioned on the other hand, and toxicological hypotheses or evidence available on PubMed/Medline and Google Scholar. RESULTS: Few post-zombification observations exist, but 20th-century studies clarified the physio pathological process, confirming its reality. Wade Davis demonstrated in 1983 that zombification results from poisoning, with effects ranging from reversible to fatal, implicating substances like tetrodotoxin and datura. Nasalization can be natural or pathological, affecting various phonemes. No mutilating acts or surgery have been reported related to Haitian zombification. CONCLUSION: The pharmacological characteristics of tetrodotoxin, coupled with testimonials, present a medical hypothesis elucidating the biological mechanism underlying nasalization in this context. Given that tetrodotoxin induces flaccid paralysis as a neurotropic poison, its neurological impact could account for soft palate paralysis or spasms. Additionally, the severe hypotension induced by tetrodotoxin may elucidate oral and pharyngeal necrosis.

Expanding the repertoire of ceDAF-12 ligands for modulation of the steroid endocrine system in C. elegans.

Steroid hormones are essential for the biological processes of eukaryotic organisms. The steroid endocrine system of C. elegans, which includes dafachronic acids (DA) and the nuclear receptor ceDAF-12, provides a simple model for exploring the role of steroid hormone signaling pathways in animals. In this study, we show for the first time the feasibility of designing synthetic steroids that can modulate different physiological processes, such as development, reproduction and ageing, in relation to ceDAF-12. Our results not only confirm the conclusions derived from genetic studies linking these processes but also provide new chemical tools to selectively manipulate them, as we found that different compounds produce different phenotypic results. The structures of these compounds are much more diverse than those of endogenous hormones and analogues previously described by other researchers, allowing further development of the chemical modulation of the steroid endocrine system in C. elegans and related nematodes.

Evaluating quasi-experimental approaches for estimating epidemiological efficacy of non-randomised field trials: applications in Wolbachia interventions for dengue.

BACKGROUND: Wolbachia symbiosis in Aedes aegypti is an emerging biocontrol measure against dengue. However, assessing its real-world efficacy is challenging due to the non-randomised, field-based nature of most intervention studies. This research re-evaluates the spatial-temporal impact of Wolbachia interventions on dengue incidence using a large battery of quasi-experimental methods and assesses each method's validity. METHODS: A systematic search for Wolbachia intervention data was conducted via PUBMED. Efficacy was reassessed using commonly-used quasi-experimental approaches with extensive robustness checks, including geospatial placebo tests and a simulation study. Intervention efficacies across multiple study sites were computed using high-resolution aggregations to examine heterogeneities across sites and study periods. We further designed a stochastic simulation framework to assess the methods' ability to estimate intervention efficacies (IE). RESULTS: Wolbachia interventions in Singapore, Malaysia, and Brazil significantly decreased dengue incidence, with reductions ranging from 48.17% to 69.19%. IEs varied with location and duration. Malaysia showed increasing efficacy over time, while Brazil exhibited initial success with subsequent decline, hinting at operational challenges. Singapore's strategy was highly effective despite partial saturation. Simulations identified Synthetic Control Methods (SCM) and its variant, count Synthetic Control Method (cSCM), as superior in precision, with the smallest percentage errors in efficacy estimation. These methods also demonstrated robustness in placebo tests. CONCLUSIONS: Wolbachia interventions exhibit consistent protective effects against dengue. SCM and cSCM provided the most precise and robust estimates of IEs, validated across simulated and real-world settings.

Non-invasive urine-based ELISA using a recombinant Leishmania protein to diagnose tegumentary leishmaniasis.

The diagnosis of tegumentary leishmaniasis (TL) is hampered by variable sensitivity and/or specificity of the tests. Serological assays are suitable to diagnose visceral leishmaniasis (VL); however, they present low performance for the detection of TL cases. Additionally, blood collection to obtain patient serum represents a challenge, as it is an invasive and uncomfortable procedure, requiring laboratorial infrastructure and trained professionals. In this context, the present study proposed to evaluate patient urine to detect TL, given that this analyte has proven to be effective in ELISA experiments for the detection of VL cases. For this, a Leishmania protein called LiHyV, two specific B-cell epitopes derived from protein amino acid sequence, and a Leishmania antigenic extract (SLA) were used as antigens. A total of 215 paired urine and serum samples were evaluated, and results showed that, when serum was employed as an analyte, rLiHyV, Peptide1, Peptide2, and SLA presented a sensitivity of 85 %, 29 %, 58 %, and 31 %, respectively, and a specificity of 97.5 %, 98 %, 100 %, and 97.5 %, respectively, in the diagnosis of TL. When urine was used, rLiHyV, Peptide1, Peptide2, and SLA presented a sensitivity of 95 %, 74 %, 67 %, and 52 %, respectively, and a specificity of 100 %, 99 %, 98 %, and 86 %, respectively. In conclusion, preliminary data suggest that urine could be considered as an alternative biological sample for the detection of TL cases.

Multitarget Compounds for Neglected Diseases: A Review.

Neglected diseases are a group of infectious diseases, many of them parasitic, that mainly affect the poorest populations with limited access to health services, especially those living in remote rural areas and slums. According to the World Health Organization (WHO), neglected diseases put the lives of more than 200 million people at risk, and treatment is made difficult by the occurrence of resistance to existing medications, as well as the high level of toxicity. In this way, the potential of multitarget compounds is highlighted, defined as compounds designed to modulate multiple targets of relevance to disease, with the overall goal of enhancing efficacy and/or improving safety. Thus, the objective of our study is to evaluate existing multitarget compound approaches for neglected diseases, with an emphasis on Leishmaniasis, Chagas Disease, and Arboviruses. A literature review was performed by searching the database "Web of Sciences". In relation to the diseases covered in this work, Leishmaniasis, individually, was the one that presented the largest number of articles (11) that dealt with the topic, which can be justified by the high prevalence of this disease in the world, the second most common disease was Dengue, followed by Chagas disease, Chikungunya virus, and Zika virus. Furthermore, the multitarget potential of phenolic compounds was observed in all diseases under study, with the mechanisms related to the nucleus and transcription being the most reported mechanisms. From this perspective, it is worth highlighting the effectiveness of approaches related to multitarget drugs in discovering new therapeutic agents for neglected diseases.

Biosynthesis of Arcyriaflavin F from Streptomyces venezuelae ATCC 10712.

Indolocarbazoles are natural products with a broad spectrum of bioactivity. A distinct feature of indolocarbazole biosynthesis is the modification of the indole and maleimide rings by regioselective tailoring enzymes. Here, we study a new indolocarbazole variant, which is encoded by the acfXODCP genes from Streptomyces venezuelae ATCC 10712. We characterise the pathway by expressing the acfXODCP genes in Streptomyces coelicolor, which led to the production of a C-5/C-5'-dihydroxylated indolocarbazole, which we assign as arcyriaflavin F. We also show that a flavin-dependent monooxygenase AcfX catalyses the C-5/C-5' dihydroxylation of the unsubstituted arcyriaflavin A into arcyriaflavin F. Interestingly, AcfX shares homology to EspX from erdasporine A biosynthesis, which instead catalyses a single C-6 indolocarbazole hydroxylation. In summary, we report a new indolocarbazole biosynthetic pathway and a regioselective C-5 indole ring tailoring enzyme AcfX.

Latent Space Representations for Marker-Less Realtime Hand-Eye Calibration.

Marker-less hand-eye calibration permits the acquisition of an accurate transformation between an optical sensor and a robot in unstructured environments. Single monocular cameras, despite their low cost and modest computation requirements, present difficulties for this purpose due to their incomplete correspondence of projected coordinates. In this work, we introduce a hand-eye calibration procedure based on the rotation representations inferred by an augmented autoencoder neural network. Learning-based models that attempt to directly regress the spatial transform of objects such as the links of robotic manipulators perform poorly in the orientation domain, but this can be overcome through the analysis of the latent space vectors constructed in the autoencoding process. This technique is computationally inexpensive and can be run in real time in markedly varied lighting and occlusion conditions. To evaluate the procedure, we use a color-depth camera and perform a registration step between the predicted and the captured point clouds to measure translation and orientation errors and compare the results to a baseline based on traditional checkerboard markers.

Performance Assessment of Object Detection Models Trained with Synthetic Data: A Case Study on Electrical Equipment Detection.

This paper explores a data augmentation approach for images of rigid bodies, particularly focusing on electrical equipment and analogous industrial objects. By leveraging manufacturer-provided datasheets containing precise equipment dimensions, we employed straightforward algorithms to generate synthetic images, permitting the expansion of the training dataset from a potentially unlimited viewpoint. In scenarios lacking genuine target images, we conducted a case study using two well-known detectors, representing two machine-learning paradigms: the Viola-Jones (VJ) and You Only Look Once (YOLO) detectors, trained exclusively on datasets featuring synthetic images as the positive examples of the target equipment, namely lightning rods and potential transformers. Performances of both detectors were assessed using real images in both visible and infrared spectra. YOLO consistently demonstrates F1 scores below 26% in both spectra, while VJ's scores lie in the interval from 38% to 61%. This performance discrepancy is discussed in view of paradigms' strengths and weaknesses, whereas the relatively high scores of at least one detector are taken as empirical evidence in favor of the proposed data augmentation approach.

Dispersion analysis of the 2017 Persian Gulf oil spill based on remote sensing data and numerical modelling.

Oil spills, detected by SAR sensors as dark areas, are highly effective marine pollutants that affect the ocean surface. These spills change the water surface tension, attenuating capillary gravitational waves and causing specular reflections. We conducted a case study in the Persian Gulf (Arabian Sea to the Strait of Hormuz), where approximately 163,900 gal of crude oil spilled in March 2017. Our study examined the relationship between oil weathering processes and extracted backscatter values using zonal slices projected over SAR-detected oil spills. Internal backscatter values ranged from -22.5 to -23.5, indicating an oil chemical binding and minimal interaction with seawater. MEDSLIK-II simulations indicated increased oil solubilization and radar attenuation rates with wind, facilitating coastal dispersion. Higher backscatter at the spill edges compared to the core reflected different stages of oil weathering. These results highlight the complex dynamics of oil spills and their environmental impact on marine ecosystems.

In vitro analysis of postbiotic antimicrobial activity against Candida Species in a minimal synthetic model simulating the gut mycobiota in obesity.

Gut fungal imbalances, particularly increased Candida spp., are linked to obesity. This study explored the potential of Lactiplantibacillus plantarum cell-free extracts (postbiotics) to modulate the growth of Candida albicans and Candida kefyr, key members of the gut mycobiota. A minimal synthetic gut model was employed to evaluate the effects of Lactiplantibacillus plantarum postbiotics on fungal growth in mono- and mixed cultures. Microreactors were employed for culturing, fungal growth was quantified using CFU counting, and regression analysis was used to evaluate the effects of postbiotics on fungal growth. Postbiotics at a concentration of 12.5% significantly reduced the growth of both Candida species. At 24 h, both C. albicans and C. kefyr in monocultures exhibited a decrease in growth of 0.11 log CFU/mL. In contrast, mixed cultures showed a more pronounced antifungal effect, with C. albicans and C. kefyr reductions of 0.62 log CFU/mL and 0.64 log CFU/mL, respectively. Regression analysis using the Gompertz model supported the antifungal activity of postbiotics and revealed species-specific differences in growth parameters. These findings suggest that L. plantarum postbiotics have the potential to modulate the gut mycobiota by reducing Candida growth, potentially offering a therapeutic approach for combating fungal overgrowth associated with obesity.

Synthetic Tetraploid of Oncidium crispum Lodd. (Orchidaceae).

In ornamental plants, artificial polyploidization has enabled the creation of new cultivars. Due to their high commercial value in the international flower market and their ornamental characteristics, such as the shape, size, color, and durability of their flower, orchids have received great attention in studies of artificial polyploidization. Here we described the protocol used for polyploid induction in Oncidium crispum, an epiphyte species native of southeastern Brazil, of great ornamental interest and widely sold in flower shops. The species stands out for having inflorescence with large flowers, brown in color with yellow spots. In addition, O. crispum has great potential for use in genetic improvement programs since the species is widely used in interspecific crosses. Closed capsules containing mature O. crispum seeds were subjected to running sterilized water for 10 min and then to a 1.5% sodium hypochlorite solution for 10 min. Small portions of seeds were introduced into 50 mL of water-soluble fertilizer with macro- and micronutrients (B>M) plus 0.7% agar. Explants originating from seeds previously in vitro germinated were submitted to 0.05% and 0.1% of colchicine for 4 days and 8 days. Flow cytometry and chromosome counts confirmed that the protocol successfully produced synthetic polyploid plants.

Additive Manufacturing Titanium Dental Implants Placed in Sinuses Grafted with 70HA:30-TCP: A One-Year Retrospective Study for Evaluation of Survival Rate.

The present short-term retrospective study evaluated the implant survival rate and peri-implant bone loss around additive-manufactured titanium implants placed in sinuses grafted with Plenum Osshp (Plenum Bioengenharia, Jundia, SP, Brazil) (70HA:30ß-TCP) material. A total of 39 implants were inserted after 23 sinus floor elevation procedures in 16 consecutive patients. Prosthetic rehabilitation included fixed partial prostheses (three units), single crowns (eleven units), and fixed full arches (three units). Clinical and radiographic parameters of implant-supported restorations were evaluated after at least one year of occlusal loading. The implant-crown success criteria included the absence of pain, suppuration, and clinical mobility, an average distance between the implant shoulder and the first visible bone contact (DIB) < 1.0 mm from the initial surgery, and the absence of prosthetic complications at the implant-abutment interface. The overall cumulative implant survival rate was 97.43%. No prosthetic complications at the implant-abutment interface were reported. After one year, the mean DIB was 0.23 mm ± 0.14. Within the limits of this retrospective study, it can be concluded that 70 HA:30 ß-TCP allowed stable and reliable bone support to maintain healthy conditions around titanium dental implants produced by additive manufacturing.

Applications of the Methylotrophic Yeast Komagataella phaffii in the Context of Modern Biotechnology.

Komagataella phaffii (formerly Pichia pastoris) is a methylotrophic yeast widely used in laboratories around the world to produce recombinant proteins. Given its advantageous features, it has also gained much interest in the context of modern biotechnology. In this review, we present the utilization of K. phaffii as a platform to produce several products of economic interest such as biopharmaceuticals, renewable chemicals, fuels, biomaterials, and food/feed products. Finally, we present synthetic biology approaches currently used for strain engineering, aiming at the production of new bioproducts.

Synthetic Colors in Food: A Warning for Children's Health.

This study addressed the harmful effects of artificial colors in pediatric populations, including children diagnosed with Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD), as well as those without behavioral disorders. There is a consensus that synthetic food colorings have several impacts on consumers, especially pediatrics, due to their influence on sensory appeal, which can encourage preference for certain foods. The results revealed that these color additives are directly linked to a series of health problems, with a greater impact on children, including a predisposition to pathological conditions such as carcinogenic, allergenic, mutagenic, cytotoxic, and clastogenic activities, as well as gastrointestinal and respiratory problems, in addition to behavioral changes in children with and without diagnosed disorders. The harms of synthetic dyes in children with or without comorbidities are worrying and require a careful and proactive approach from parents, caregivers and public authorities.

A Review of EPDM (Ethylene Propylene Diene Monomer) Rubber-Based Nanocomposites: Properties and Progress.

Ethylene propylene diene monomer (EPDM) is a synthetic rubber widely used in industry and commerce due to its high thermal and chemical resistance. Nanotechnology has enabled the incorporation of nanomaterials into polymeric matrixes that maintain their flexibility and conformation, allowing them to achieve properties previously unattainable, such as improved tensile and chemical resistance. In this work, we summarize the influence of different nanostructures on the mechanical, thermal, and electrical properties of EPDM-based materials to keep up with current research and support future research into synthetic rubber nanocomposites.

Larvicidal activity of coumarin derivatives on Toxocara canis larvae, cytotoxicity analysis, and in silico bioavailability studies.

Human toxocariasis is a neglected anthropozoonosis with global distribution. Treatment is based on the administration of anthelmintics; however, their effectiveness at the tissue level is low to moderate, necessitating the discovery of new drug candidates. Several groups of synthetic compounds, including coumarin derivatives, have demonstrated bioactivity against fungi, bacteria, and even parasites, such as Dactylogyrus intermedius, Leishmania major, and Plasmodium falciparum. The aim of this study was to evaluate the effect of ten coumarin-derived compounds against Toxocara canis larvae using in vitro, cytotoxicity, and in silico tests for selecting new drug candidates for preclinical tests aimed at evaluating the treatment of visceral toxocariasis. The compounds were tested in vitro in duplicate at a concentration of 1 mg/mL, and compounds with larvicidal activity were serially diluted to obtain concentrations of 0.5 mg/mL; 0.25 mg/mL; 0.125 mg/mL; and 0.05 mg/mL. The tests were performed in a microculture plate containing 100 T. canis larvae in RPMI-1640 medium. One compound (COU 9) was selected for cytotoxicity analysis using J774.A1 murine macrophages and it was found to be non-cytotoxic at any concentration tested. The in silico analysis was performed using computational models; the compound presented adequate results of oral bioavailability. To confirm the non-viability of the larvae, the contents of the microplate wells of COU 9 were inoculated intraperitoneally (IP) into female Swiss mice at 7-8 weeks of age. This confirmed the larvicidal activity of this compound. These results show that COU 9 exhibited larvicidal activity against T. canis larvae, which, after exposure to the compound, were non-viable, and that COU 9 inhibited infection in a murine model. In addition, COU 9 did not exhibit cytotoxicity and presented adequate bioavailability in silico, similar to albendazole, an anthelmintic, which is the first choice for treatment of human toxocariasis, supporting the potential for future investigations and preclinical tests on COU 9.

Geospatial analysis of cardiovascular mortality before and during the COVID-19 pandemic in Peru: analysis of the national death registry to support emergency management in Peru.

Background: COVID-19 has led to significant global mortality, with Peru being among the countries most affected. While pre-existing comorbidities have been linked to most cases, the exact distribution of fatalities within the country remains unclear. We aimed to assess deaths attributed to cardiovascular diseases (CVD) before and during the COVID-19 pandemic across various regions and provinces in Peru. Methods: An observational georeferencing study was designed. Peru faced four waves of COVID-19 over three years, with variable impacts across its three regions (Coast, Highlands, and Jungle). Deaths related to cardiovascular diseases, such as heart failure (HF), arrhythmia, acute myocardial infarction (AMI), strokes, and acute coronary syndrome, were examined as primary variables. The study period spanned pre-pandemic years (2017-2019) and pandemic years (2020-2021), utilizing death data from the National Death Information System (SINADEF). The georeferencing analysis was conducted using ArcGIS v10.3. Results: A total of 28,197 deaths were recorded during the study period, with significant increases during the pandemic (2020-2021). Cardiovascular deaths were disproportionately higher during the pandemic, totaling 19,376 compared to 8,821 in the pre-pandemic period (p < 0.001). AMI and HF were the leading causes of mortality, showing significant increases from the pre-pandemic (5,573 and 2,584 deaths) to the pandemic period (12,579 and 5,628 deaths), respectively. Deaths due to CVD predominantly affected individuals aged over 60, with significant increases between the two study periods (7,245 vs. 16,497 deaths, p = 0.002). Geospatial analysis revealed regional disparities in CVD mortality, highlighting provinces like Lima and Callao as COVID-19 critical areas. The substantial increase in cardiovascular deaths during the COVID-19 pandemic in Peru showed distinctive patterns across regions and provinces. Conclusions: Geospatial analysis identified higher-risk areas and can guide specific interventions to mitigate the impact of future health crises. Understanding the dynamic relationship between pandemics and cardiovascular health is crucial for effective public health strategies.