Complete blood count as a biomarker for preeclampsia with severe features diagnosis: a machine learning approach.

OBJECTIVE: This study introduces the complete blood count (CBC), a standard prenatal screening test, as a biomarker for diagnosing preeclampsia with severe features (sPE), employing machine learning models. METHODS: We used a boosting machine learning model fed with synthetic data generated through a new methodology called DAS (Data Augmentation and Smoothing). Using data from a Brazilian study including 132 pregnant women, we generated 3,552 synthetic samples for model training. To improve interpretability, we also provided a ridge regression model. RESULTS: Our boosting model obtained an AUROC of 0.90±0.10, sensitivity of 0.95, and specificity of 0.79 to differentiate sPE and non-PE pregnant women, using CBC parameters of neutrophils count, mean corpuscular hemoglobin (MCH), and the aggregate index of systemic inflammation (AISI). In addition, we provided a ridge regression equation using the same three CBC parameters, which is fully interpretable and achieved an AUROC of 0.79±0.10 to differentiate the both groups. Moreover, we also showed that a monocyte count lower than 490 / m m 3 yielded a sensitivity of 0.71 and specificity of 0.72. CONCLUSION: Our study showed that ML-powered CBC could be used as a biomarker for sPE diagnosis support. In addition, we showed that a low monocyte count alone could be an indicator of sPE. SIGNIFICANCE: Although preeclampsia has been extensively studied, no laboratory biomarker with favorable cost-effectiveness has been proposed. Using artificial intelligence, we proposed to use the CBC, a low-cost, fast, and well-spread blood test, as a biomarker for sPE.

Antitumoral and Antiproliferative Potential of Synthetic Derivatives of Scorpion Peptide IsCT1 in an Oral Cavity Squamous Carcinoma Model.

The oral cavity is a frequent site for head and neck cancers, which rank as the sixth most common cancer globally, with a 5-year survival rate slightly over 50%. Current treatments are limited, and resistance to therapy remains a significant clinical obstacle. IsCT1, a membrane-active peptide derived from the venom of the scorpion Opisthacanthus madagascariensis, has shown antitumor effects in various cancer cell lines, including breast cancer and chronic myeloid leukemia. However, its hemolytic action limits its potential therapeutic use. This study aims to assess the antitumor and antiproliferative activities of synthetic peptides derived from IsCT1 (IsCT-P, AC-AFPK-IsCT1, AFPK-IsCT1, AC-KKK-IsCT1, and KKK-IsCT1) in the context of oral squamous cell carcinoma. We evaluated the cytotoxic effects of these peptides on tongue squamous cell carcinoma cells and normal cells, as well as their impact on cell cycle phases, the expression of proliferation markers, modulators of cell death pathways, and mitochondrial potential. Our results indicate that the IsCT1 derivatives IsCT-P and AC-AFPK-IsCT1 possess cytotoxic properties towards squamous cell carcinoma cells, reducing mitochondrial membrane potential and the proliferative index. The treatment of cancer cells with AC-AFPK-IsCT1 led to a positive modulation of pro-apoptotic markers p53 and caspases 3 and 8, a decrease in PCNA and Cyclin D1 expression, and cell cycle arrest in the S phase. Notably, contrary to the parental IsCT1 peptide, AC-AFPK-IsCT1 did not exhibit hemolytic activity or cytotoxicity towards normal cells. Therefore, AC-AFPK-IsCT1 might be a viable therapeutic option for head and neck cancer treatment.

Exploring the biocatalysis of psilocybin and other tryptamines: Enzymatic pathways, synthetic strategies, and industrial implications.

Tryptamines play diverse roles as neurotransmitters and psychoactive compounds found in various organisms. Psilocybin, a notable tryptamine, has garnered attention for its therapeutic potential in treating mental health disorders like depression and anxiety. Despite its promising applications, current extraction methods for psilocybin are labor-intensive and economically limiting. We suggest biocatalysis as a sustainable alternative, leveraging enzymes to synthesize psilocybin and other tryptamines efficiently. By elucidating psilocybin biosynthesis pathways, researchers aim to advance synthetic methodologies and industrial applications. This review underscores the transformative potential of biocatalysis in enhancing our understanding of tryptamine biosynthesis and facilitating the production of high-purity psilocybin and other tryptamines for therapeutic and research use.

Identification of novel broad host-range promoter sequences functional in diverse Pseudomonadota by a promoter-trap approach.

Finding novel promoter sequences is a cornerstone of synthetic biology. To contribute to the expanding catalog of biological parts, we employed a promoter-trap approach to identify novel sequences within an Antarctic microbial community that act as broad host-range promoters functional in diverse Pseudomonadota. Using Pseudomonas putida KT2440 as host, we generated a library comprising approximately 2,000 clones resulting in the identification of thirteen functional promoter sequences, thereby expanding the genetic toolkit available for this chassis. Some of the discovered promoter sequences prove to be broad host-range as they drove gene expression not only in P. putida KT2440 but also in Escherichia coli DH5α, Cupriavidus taiwanensis R1T, Paraburkholderia phymatum STM 815T, Ensifer meliloti 1021, and an indigenous Antarctic bacterium, Pseudomonas sp. UYIF39. Our findings enrich the existing catalog of biological parts, offering a repertoire of broad host-range promoter sequences that exhibit functionality across diverse members of the phylum Pseudomonadota, proving Antarctic microbial community as a valuable resource for prospecting new biological parts for synthetic biology.

Effects of LED lights and cytokinin on the phytotreatment of simulated swine wastewater by Azolla spp.: Pollutant removal and biomass valorization.

Phytoremediation is an eco-friendly and affordable option for tackling wastewater pollutants. The study focused on how light-emitting diodes (LED) light exposure, measured by intensity and duration (photoperiod), along with cytokinin, impacts Azolla microphylla's simulated swine wastewater treatment performance and biomass production. Under optimal treatment conditions, high removals of COD (89.2 % to 90.8 %), N-NH4+ (72.6 % to 91.2 %), N-NO3- (84.4 % to 88.6 %), Cu (75.4 % to 86.4 %), sulfamethoxazole (77.0 % to 79.0 %), P-PO43- (54.1 % to 59.9 %) and DOC (67.4 % to 71.3 %) while Zn presented a more moderate reduction (2.0 % to 9.7 %). Biomass productivity reached up to 34.8 t ha-1 yr-1. Protein production accounted for 23 % to 27 % of dry weight, while lipids ranged from 20 % to 34 % of dry biomass. Carbohydrate content varied from 8 % to 28 % of fresh weight. Higher light intensities, with both high or low values of photoperiods, and low concentrations of cytokinin were identified as optimal conditions for removal of almost all pollutants. However, pollutant removal was impacted differently by LED light and cytokinin concentration. In treatment conditions with the shortest photoperiods (8 h), the lowest residual Cu and Zn concentrations, whereas with longer photoperiods (24 h), the lowest residual concentrations of N-NH4+ and P-PO43- concentrations were recorded. On the other hand, SMX was the only parameter in which cytokinin had a clear influence on its removal, with the lowest residual concentration observed under 8-hour photoperiods combined with the lowest tested cytokinin concentrations (0.3 mg L-1). For residual COD and N-NO3-, no discernible pattern was evident for any of the analyzed factors. Therefore, the study demonstrates the potential for treating simulated swine wastewater using Azolla microphylla, aligned with its ability to produce biomass rich in high-value compounds.

Disentangling the Regulatory Response of Agrobacterium tumefaciens CHLDO to Glyphosate for Engineering Whole-Cell Phosphonate Biosensors.

Phosphonates (PHTs), organic compounds with a stable C-P bond, are widely distributed in nature. Glyphosate (GP), a synthetic PHT, is extensively used in agriculture and has been linked to various human health issues and environmental damage. Given the prevalence of GP, developing cost-effective, on-site methods for GP detection is key for assessing pollution and reducing exposure risks. We adopted Agrobacterium tumefaciens CHLDO, a natural GP degrader, as a host and the source of genetic parts for constructing PHT biosensors. In this bacterial species, the phn gene cluster, encoding the C-P lyase pathway, is regulated by the PhnF transcriptional repressor. We selected the phnG promoter, which displays a dose-dependent response to GP, to build a set of whole-cell biosensors. Through stepwise genetic optimization of the transcriptional cascade, we created a whole-cell biosensor capable of detecting GP in the 0.25-50 µM range in various samples, including soil and water.

In silico approach revealed the membrane receptor PHO36 as a new target for synthetic anticandidal peptides.

Aim: Synthetic antimicrobial peptides (SAMPs) present the potential to fight systemic fungal infections. Here, the PHO36 receptor from Candida albicans was analyzed by in silico tools as a possible target for three anticandidal SAMPs: RcAlb-PepIII, PepGAT and PepKAA.Materials & methods: Molecular docking, dynamics and quantum biochemistry were employed to understand the individual contribution of amino acid residues in the interaction region.Results: The results revealed that SAMPs strongly interact with the PHO36 by multiple high-energy interactions. This is the first study to employ quantum biochemistry to describe the interactions between SAMPs and the PHO36 receptor.Conclusion: This work contributes to understanding and identifying new molecular targets with medical importance that could be used to discover new drugs against systemic fungal infections.

Here, computers helped us find new proteins in Candida albicans that may guide the development of new medicines.

A Deep Learning Approach to Distance Map Generation Applied to Automatic Fiber Diameter Computation from Digital Micrographs.

Precise measurement of fiber diameter in animal and synthetic textiles is crucial for quality assessment and pricing; however, traditional methods often struggle with accuracy, particularly when fibers are densely packed or overlapping. Current computer vision techniques, while useful, have limitations in addressing these challenges. This paper introduces a novel deep-learning-based method to automatically generate distance maps of fiber micrographs, enabling more accurate fiber segmentation and diameter calculation. Our approach utilizes a modified U-Net architecture, trained on both real and simulated micrographs, to regress distance maps. This allows for the effective separation of individual fibers, even in complex scenarios. The model achieves a mean absolute error (MAE) of 0.1094 and a mean square error (MSE) of 0.0711, demonstrating its effectiveness in accurately measuring fiber diameters. This research highlights the potential of deep learning to revolutionize fiber analysis in the textile industry, offering a more precise and automated solution for quality control and pricing.

Natural and Synthetic Capsaicin Analogues: A Comprehensive Review of Biological Effects and Synthetic Pathways.

Capsaicin analogs, whether sourced from natural origins or synthesized de novo, have garnered significant attention across diverse scientific disciplines. This comprehensive investigation explores the expansive domain of medicinal chemistry and pharmacology, focusing on capsaicin and its analogs. Notably, these analogs exhibit a wideranging pharmacological spectrum, with a particular emphasis on their potent antitumor properties. Researchers frequently explore structural modifications, particularly in region C, consistently enhancing their pharmacological activities. A highlighted finding is that analogs with alterations in both regions A and C manifest a diverse array of effects, spanning from anti-obesity to protection against ischemia. They also demonstrate anti- Alzheimer's, anti-fibrotic, anti-inflammatory, anti-diabetic, antimalarial, and anti-epileptic properties. This underscores the potential of structural adaptations in these regions, expanding the therapeutic applications of capsaicin-like compounds. Additionally, manipulations in regions B and C result in compounds that possess antioxidant and anti-obesity properties, providing valuable insights for the development of novel compounds. The therapeutic potential of capsaicin analogs opens innovative avenues for drug design and development, promising to address a broad spectrum of diseases and enhance global quality of life. Moreover, this article meticulously examines various synthetic methodologies for synthesizing capsaicin analogs, complementing the main review. These methodologies distinguish themselves through their simplicity, mild reaction conditions, and reliance on readily available commercial reagents. The accessible synthesis pathways enable researchers from diverse backgrounds to explore these compounds, fostering investigations and potential therapeutic applications.

A Multi-Epitope Protein for High-Performance Serodiagnosis of Chronic Chagas Disease in ELISA and Lateral Flow Platforms.

We developed a protein to rapidly and accurately diagnose Chagas disease, a life-threatening illness identified by the WHO as a critical worldwide public health risk. Limitations in present day serological tests are complicating the current health situation and contributing to most infected persons being unaware of their condition and therefore untreated. To improve diagnostic testing, we developed an immunological mimic of the etiological agent, Trypanosoma cruzi, by combining ten pathogen-specific epitopes within the beta-barrel protein structure of Thermal Green Protein. The resulting multi-epitope protein, DxCruziV3, displayed high specificity and sensitivity as the antibody capture reagent in an ELISA platform with an analytical sensitivity that exceeds WHO recommendations. Within an immunochromatographic platform, DxCruziV3 showed excellent performance for the point of application diagnosis in a region endemic for multiple diseases, the municipality of Barcelos in the state of Amazonas, Brazil. In total, 167 individuals were rapidly tested using whole blood from a finger stick. As recommended by the Brazilian Ministry of Health, venous blood samples were laboratory tested by conventional assays for comparison. Test results suggest utilizing DxCruziV3 in different assay platforms can confidently diagnose chronic infections by T. cruzi. Rapid and more accurate results will benefit everyone but will have the most noticeable impact in resource-limited rural areas where the disease is endemic.

Replication of the Venezuelan Equine Encephalitis Vaccine from a Synthetic PCR Fragment.

BACKGROUND/OBJECTIVES: There is no approved human vaccine for Venezuelan equine encephalitis (VEE), a life-threatening disease caused by the VEE virus (VEEV). In previous studies, plasmid DNA encoding the full-length RNA genome of the VEE V4020 vaccine was used for the preparation of experimental live virus VEE vaccines in the plasmid-transfected cell culture. METHODS: Here, we used the high-fidelity polymerase chain reaction (PCR) to prepare synthetic, transcriptionally active PCR (TAP) fragments encoding the V4020 genome. RESULTS: TAP fragment initiated the replication of the V4020 live virus vaccine in TAP fragment-transfected cells. A transfection of less than 1 ug of TAP fragment resulted in the replication of the V4020 vaccine virus in CHO cells. CONCLUSION: We conclude that not only plasmid DNA but also synthetic PCR-generated DNA fragments can be used for the manufacturing of live vaccines for VEEV and, potentially, other viruses.

More doctors, better health? A generalised synthetic control approach to estimating impacts of increasing doctors under Brazil's Mais Medicos programme.

Worldwide, there are an insufficient number of primary care physicians to provide accessible, high-quality primary care services. Better knowledge on the health impacts of policies aimed at improving access to primary care physicians is important for informing future policies. Using a generalised synthetic control estimator (GSC), we estimate the effect of the increase in primary care physicians from the Programa Mais Médicos in Brazil. The GSC allows us to estimates a continuous treatment effects which are heterogenous by region. We exploit the variation in physicians allocated to each Brazilian microregion to identify the impact of an increasing Mais Médicos primary care physicians. We explore hospitalisations and mortality rates (both total and from ambulatory care sensitive conditions) as outcomes. Our analysis differs from previous work by estimating the impact of the increase in physician numbers, as opposed to the overall impact of programme participation. We examine the impact on hospitalisations and mortality rates and employ a panel dataset with monthly observations of all Brazilian microregion over the period 2008-2017. We find limited effects of an increase in primary care physicians impacting health outcomes - with no significant impact of the Programa Mais Médicos on hospitalisations or mortality rates. Potential explanations include substitution of other health professionals, impacts materialising over the longer-term, and poor within-region allocation of Mais Médicos physicians.

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.

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.

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.

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.