Investigating a new approach for magnetic ionic liquids: Dispersive liquid-liquid microextraction coupled to pyrolysis gas-chromatography-mass spectrometry to determine flame retardants in sewage sludge samples.

This study addresses the analysis of emerging contaminants, often using chromatographic techniques coupled to mass spectrometry. However, sample preparation is often required prior to instrumental analysis, and dispersive liquid-liquid microextraction (DLLME) is a viable strategy in this context. DLLME stands out for its ability to reduce sample and solvent volumes. Notably, dispersive liquid-liquid microextraction using magnetic ionic liquids (MILs) has gained relevance due to the incorporation of paramagnetic components in the chemical structure, thereby eliminating the centrifugation step. A pyrolizer was selected in this work to introduce sample onto the GC column, since the MIL is extremely viscous and incompatible with direct introduction through an autosampler. This study is the first to report the use of a DLLME/MIL technique for sample introduction through a pyrolizer in gas chromatography coupled to mass spectrometry (GC-MS). This approach enables the MIL to be compatible with gas chromatography systems, resulting in optimized analytical and instrument performance. The analysis of polybrominated diphenyl ether flame retardants (PBDEs) was focused on the PBDE congeners 28, 47, 99, 100, and 153 in sewage sludge samples. The [P6,6,6,14+]2[MnCl42-] MIL was thoroughly characterized using UV-Vis, Fourier transform infrared spectroscopy (FTIR), and Raman spectroscopy, as well as thermal analysis. In the chromatographic method, a pyrolyzer was used in the sample introduction step (Py-GC-MS), and critical injection settings were optimized using multivariate approaches. Optimized conditions were achieved with a temperature of 220 °C, a pyrolysis time of 0.60 min, and an injection volume of 9.00 µL. DLLME optimization was performed through central compound planning (CCD), and optimized training conditions were achieved with 10.0 mg of MIL, 3.00 µL of acetonitrile (ACN) as dispersive solvent, extraction time of 60 s, and volume of a sample of 8.50 mL. Precision was observed to range from 0.11 % to 12.5 %, with limits of detection (LOD) of 44.4 µg L-1 for PBDE 28, 16.9 µg L-1 for PBDE 47 and PBDE 99, 33.0 µg L-1 for PBDE 100 and 375 µg L-1 for PBDE 153. PBDE 28 was identified and analyzed in the sludge sample at a concentration of 800 µg L-1. The use of MIL in dispersive liquid-liquid microextraction combined with pyrolysis gas chromatography-mass spectrometry enables identification and quantification of PBDEs in sewage sludge samples at concentrations down to the µg L-1 level.

Effect of resistance training on quadriceps femoris muscle thickness obtained by ultrasound: A systematic review with meta-analysis.

OBJECTIVE: The present study aimed to determine the magnitude and intervention time of resistance training required to generate adaptations in the muscle thickness of the quadriceps muscle obtained by ultrasound in healthy adults. METHOD: A systematic review with meta-analysis was conducted on studies recovered from Pubmed, Web of Science, and Scopus databases up to March 2022. The study selection process was carried out by two independent researchers, with the presence of a third researcher in case of disagreements. The methodological quality of the studies was determined with the TESTEX scale, and the risk of bias analysis was determined using Cochrane's RoB 2.0 tool. The meta-analysis used the inverse of the variance with a fixed model, and the effect size was reported by the standardized mean difference (SMD) with a confidence interval of 95%. RESULTS: Ten studies were included in a meta-analysis. The overall analysis of the studies demonstrated an SMD = 0.35 [95% CI: 0.13-0.56] (P = 0.002), with a low heterogeneity of I2 = 0% (P = 0.52). No publication bias was detected using a funnel plot followed by Egger's test (P = 0.06). The degree of certainty of the meta-analysis was high using the GRADE tool. CONCLUSION: We found that resistance training can generate significant average increases of 16.6% in muscle thickness obtained by ultrasound in the quadriceps femoris muscles of healthy adults. However, the subgroup analysis showed that significant effect sizes were only observed after eight weeks of training.

Overview of the Metabolite Composition and Antioxidant Capacity of Seven Major and Minor Cereal Crops and Their Milling Fractions.

Cereal grains play an important role in human health as a source of macro- and micronutrients, besides phytochemicals. The metabolite diversity was investigated in cereal crops and their milling fractions by untargeted metabolomics ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) of 69 samples: 7 species (barley, oat, pearl millet, rye, sorghum, triticale, and wheat), 23 genotypes, and 4 milling fractions (husk, bran, flour, and wholegrain). Samples were also analyzed by in vitro antioxidant activity. UHPLC-MS/MS signals were processed using XCMS, and metabolite annotation was based on SIRIUS and GNPS libraries. Bran and husk showed the highest antioxidant capacity and phenolic content/diversity. The major metabolite classes were phenolic acids, flavonoids, fatty acyls, and organic acids. Sorghum, millet, barley, and oats showed distinct metabolite profiles, especially related to the bran fraction. Molecular networking and chemometrics provided a comprehensive insight into the metabolic profiling of cereal crops, unveiling the potential of coproducts and super cereals such as sorghum and millet as sources of polyphenols.

plantMASST - Community-driven chemotaxonomic digitization of plants.

Understanding the distribution of hundreds of thousands of plant metabolites across the plant kingdom presents a challenge. To address this, we curated publicly available LC-MS/MS data from 19,075 plant extracts and developed the plantMASST reference database encompassing 246 botanical families, 1,469 genera, and 2,793 species. This taxonomically focused database facilitates the exploration of plant-derived molecules using tandem mass spectrometry (MS/MS) spectra. This tool will aid in drug discovery, biosynthesis, (chemo)taxonomy, and the evolutionary ecology of herbivore interactions.

Implementation of multiomic mass spectrometry approaches for the evaluation of human health following environmental exposure.

Omics analyses collectively refer to the possibility of profiling genetic variants, RNA, epigenetic markers, proteins, lipids, and metabolites. The most common analytical approaches used for detecting molecules present within biofluids related to metabolism are vibrational spectroscopy techniques, represented by infrared, Raman, and nuclear magnetic resonance (NMR) spectroscopies and mass spectrometry (MS). Omics-based assessments utilizing MS are rapidly expanding and being applied to various scientific disciplines and clinical settings. Most of the omics instruments are operated by specialists in dedicated laboratories; however, the development of miniature portable omics has made the technology more available to users for field applications. Variations in molecular information gained from omics approaches are useful for evaluating human health following environmental exposure and the development and progression of numerous diseases. As MS technology develops so do statistical and machine learning methods for the detection of molecular deviations from personalized metabolism, which are correlated to altered health conditions, and they are intended to provide a multi-disciplinary overview for researchers interested in adding multiomic analysis to their current efforts. This includes an introduction to mass spectrometry-based omics technologies, current state-of-the-art capabilities and their respective strengths and limitations for surveying molecular information. Furthermore, we describe how knowledge gained from these assessments can be applied to personalized medicine and diagnostic strategies.

Enhancing RECK Expression Through miR-21 Inhibition: A Promising Strategy for Bladder Carcinoma Control.

Bladder carcinoma (BC) is the tenth most frequent malignancy worldwide, with high morbidity and mortality rates. Despite recent treatment advances, high-grade BC and muscle-invasive BC present with significant progression and recurrence rates, urging the need for alternative treatments. The microRNA-21 (miR-21) has superexpression in many malignancies and is associated with cellular invasion and progression. One of its mechanisms of action is the regulation of RECK, a tumor suppressor gene responsible for inhibiting metalloproteinases, including MMP9. In a high-grade urothelial cancer cell line, we aimed to assess if miR-21 downregulation would promote RECK expression and decrease MMP9 expression. We also evaluated cellular migration and proliferation potential by inhibition of this pathway. In a T24 cell line, we inhibited miR-21 expression by transfection of a specific microRNA inhibitor (anti-miR-21). There were also control and scramble groups, the last with a negative microRNA transfected. After the procedure, we performed a genetic expression analysis of miR-21, RECK, and MMP9 through qPCR. Migration, proliferation, and protein expression were evaluated via wound healing assay, colony formation assay, flow cytometry, and immunofluorescence.After anti-miR-21 transfection, miR-21 expression decreased with RECK upregulation and MMP9 downregulation. The immunofluorescence assay showed a significant increase in RECK protein expression (p < 0.0001) and a decrease in MMP9 protein expression (p = 0.0101). The anti-miR-21 transfection significantly reduced cellular migration in the wound healing assay (p < 0.0001). Furthermore, in the colony formation assay, the anti-miR-21 group demonstrated reduced cellular proliferation (p = 0.0008), also revealed in the cell cycle analysis by flow cytometry (p = 0.0038). Our results corroborate the hypothesis that miR-21 is associated with BC cellular migration and proliferation, revealing its potential as a new effective treatment for this pathology.

Synthesis and In Vitro and Silico Anti-inflammatory Activity of New Thiazolidinedione-quinoline Derivatives.

BACKGROUND: Inflammation is a series of complex defense-related reactions. The inflammation cascade produces various pro-inflammatory mediators. Unregulated production of these pro-inflammatory mediators can lead to a wide range of diseases, including rheumatoid arthritis, sepsis, and inflammatory bowel disease. In the literature, the anti-inflammatory action of quinoline and thiazolidinedione nuclei are well established, alone, and associated with other nuclei. The synthesis of hybrid molecules is a strategy for obtaining more efficient molecules due to the union of pharmacophoric nuclei known to be related to pharmacological activity. OBJECTIVE: Based on this, this work presents the synthesis of thiazolidinedione-quinoline molecular hybrids and their involvement in the modulation of cytokines involved in the inflammatory reaction cascade. METHODS: After synthesis and characterization, the compounds were submitted to cell viability test (MTT), ELISA IFN-γ and TNF-α, adipogenic differentiation, and molecular docking assay with PPARy and COX-2 targets. RESULTS: LPSF/ZKD2 and LPSF/ZKD7 showed a significant decrease in the concentration of IFN- γ and TNF-α, with a dose-dependent behavior. LPSF/ZKD4 at a concentration of 50 µM significantly reduced IL-6 expression. LPSF/ZKD4 demonstrates lipid accumulation with significant differences between the untreated and negative control groups, indicating a relevant agonist action on the PPARγ receptor. Molecular docking showed that all synthesized compounds have good affinity with PPARγ e COX-2, with binding energy close to -10,000 Kcal/mol. CONCLUSION: These results demonstrate that the synthesis of quinoline-thiazolidinedione hybrids may be a useful strategy for obtaining promising candidates for new anti-inflammatory agents.

Thiazolyl-isatin derivatives: Synthesis, in silico studies, in vitro biological profile against breast cancer cells, mRNA expression, P-gp modulation, and interactions of Akt2 and VIM proteins.

The literature reports that thiazole and isatin nuclei present a range of biological activities, with an emphasis on anticancer activity. Therefore, our proposal was to make a series of compounds using the molecular hybridization strategy, which has been used by our research group, producing hybrid molecules containing the thiazole and isatin nuclei. After structural planning and synthesis, the compounds were characterized and evaluated in vitro against breast cancer cell lines (T-47D, MCF-7 and MDA-MB-231) and against normal cells (PBMC). The activity profile on membrane proteins involved in chemoresistance and tumorigenic signaling proteins was also evaluated. Among the compounds tested, the compounds 4c and 4a stood out with IC50 values of 1.23 and 1.39 µM, respectively, against the MDA-MB-231 cell line. Both compounds exhibited IC50 values of 0.45 µM for the MCF-7 cell line. Compounds 4a and 4c significantly decreased P-gp mRNA expression levels in MCF-7, 4 and 2 folds respectively. Regarding the impact on tumorigenic signaling proteins, compound 4a inhibited Akt2 in MDA-MB-231 and compound 4c inhibited the mRNA expression of VIM in MCF-7.

microbeMASST: a taxonomically informed mass spectrometry search tool for microbial metabolomics data.

microbeMASST, a taxonomically informed mass spectrometry (MS) search tool, tackles limited microbial metabolite annotation in untargeted metabolomics experiments. Leveraging a curated database of >60,000 microbial monocultures, users can search known and unknown MS/MS spectra and link them to their respective microbial producers via MS/MS fragmentation patterns. Identification of microbe-derived metabolites and relative producers without a priori knowledge will vastly enhance the understanding of microorganisms' role in ecology and human health.

Co-occurrence network analysis reveals the alterations of the skin microbiome and metabolome in adults with mild to moderate atopic dermatitis.

Skin microbiome can be altered in patients with atopic dermatitis (AD). An understanding of the changes from healthy to atopic skin can help develop new targets for treatment by identifying microbial and molecular biomarkers. This study investigates the skin microbiome and metabolome of healthy adult subjects and lesion (ADL) and non-lesion (ADNL) of AD patients by 16S rRNA gene sequencing and mass spectrometry, respectively. Samples from AD patients showed alterations in the diversity and composition of the skin microbiome, with ADL skin having the greatest divergence. Staphylococcus species, especially S. aureus, were significantly increased in AD patients. Metabolomic profiles were also different between the groups. Dipeptide derivatives are more abundant in ADL, which may be related to skin inflammation. Co-occurrence network analysis of the microbiome and metabolomics data revealed higher co-occurrence of metabolites and bacteria in healthy ADNL compared to ADL. S. aureus co-occurred with dipeptide derivatives in ADL, while phytosphingosine-derived compounds showed co-occurrences with commensal bacteria, for example, Paracoccus sp., Pseudomonas sp., Prevotella bivia, Lactobacillus iners, Anaerococcus sp., Micrococcus sp., Corynebacterium ureicelerivorans, Corynebacterium massiliense, Streptococcus thermophilus, and Roseomonas mucosa, in healthy and ADNL groups. Therefore, these findings provide valuable insights into how AD affects the human skin metabolome and microbiome.IMPORTANCEThis study provides valuable insight into changes in the skin microbiome and associated metabolomic profiles in an adult population with mild to moderate atopic dermatitis. It also identifies new therapeutic targets that may be useful for developing personalized treatments for individuals with atopic dermatitis based on their unique skin microbiome and metabolic profiles.

Frequency of skin diseases in renal transplant recipients and patients with chronic kidney disease in a tertiary center: a cross-sectional study.

BACKGROUND: The prevalence of chronic kidney disease (CKD) has increased in the recent decades, along with the number of patients in the terminal stages of this disease, requiring transplantation. Some skin disorders are more frequent in patients with CKD and in renal transplant recipients (RTR). OBJECTIVES: To evaluate the frequency of skin diseases in RTR and patients with CKD receiving conservative treatment. DESIGN AND SETTING: This observational cross-sectional study recruited consecutive patients with CKD and RTR from a nephrology clinic at a teaching hospital in Brazil between 2015 and 2020. METHODS: Quantitative, descriptive, and analytical approaches were used. The sample was selected based on convenience sampling. Data were collected from dermatological visits and participants' medical records. RESULTS: Overall, 308 participants were included: 206 RTR (66.9%, median age: 48 years, interquartile range [IQR] 38.0-56.0, 63.6% men) and 102 patients with CKD (33.1%, median age: 61.0 years, IQR 50.0-71.2, 48% men). The frequency of infectious skin diseases (39.3% vs. 21.6% P = 0.002) were higher in RTR than in patients with CKD. Neoplastic skin lesions were present in nine (4.4%) RTR and in only one (1.0%) patient with CKD. Among the RTR, the ratio of basal cell carcinoma to squamous cell carcinoma was 2:1. CONCLUSIONS: This study revealed that an increased frequency of infectious skin diseases may be expected in patients who have undergone kidney transplantation. Among skin cancers, BCC is more frequently observed in RTR, especially in those using azathioprine.

Assessing the efficacy of the 'Bicho De 7 Cabeças' B-learning school-based program in enhancing mental health literacy and reducing stigma.

The prevalence of mental disorders in adolescents has a considerable impact on daily life, restricting tasks and diminishing overall quality of life while potentially leading to stigmatization. This study aims to measure the impact of a mental health literacy intervention program, called "Bicho de 7 Cabeças" project, in b-learning format, on the increase of knowledge and the decrease of stigma in young people from Póvoa de Varzim, in Portugal. A quasi-experimental study was conducted, from November 2022 to May 2023, involving an experimental group ("Bicho de 7 Cabeças" protocol) and an active control group (informational brochures), utilizing a pre-test/post-test design. Mental Health Literacy Measure-MHLM, Mental Health Promoting Knowledge Scale-MHPK-10, Mental Illness Knowledge Schedule-MAKS, Reported and Intended Behaviour Scale-RIBS, and Community Attitudes toward People with Mental Illness-CAMI were used. A total of 504 young students from the 9th grade enroll in this study, with a mean age around 14 years old. There is a significant difference between stigma (p <.001) and knowledge (p <.001) scores at baseline and follow-up. The results of this study shows that interventions aimed at young people for the promotion of mental health literacy and stigma reduction are needed and more initiatives should be implemented in schools to address these problems.

Advanced Tuneable Micronanoplatforms for Sensitive and Selective Multiplexed Spectroscopic Sensing via Electro-Hydrodynamic Surface Molecular Lithography.

Micro- and nanopatterning of materials, one of the cornerstones of emerging technologies, has transformed research capabilities in lab-on-a-chip diagnostics. Herein, a micro- and nanolithographic method is developed, enabling structuring materials at the submicron scale, which can, in turn, accelerate the development of miniaturized platform technologies and biomedical sensors. Underpinning it is the advanced electro-hydrodynamic surface molecular lithography, via inducing interfacial instabilities produces micro- and nanostructured substrates, uniquely integrated with synthetic surface recognition. This approach enables the manufacture of design patterns with tuneable feature sizes, which are functionalized via synthetic nanochemistry for highly sensitive, selective, rapid molecular sensing. The development of a high-precision piezoelectric lithographic rig enables reproducible substrate fabrication with optimum signal enhancement optimized for functionalization with capture molecules on each micro- and nanostructured array. This facilitates spatial separation, which during the spectroscopic sensing, enables multiplexed measurement of target molecules, establishing the detection at minute concentrations. Subsequently, this nano-plasmonic lab-on-a-chip combined with the unconventional computational classification algorithm and surface enhanced Raman spectroscopy, aimed to address the challenges associated with timely point-of-care detection of disease-indicative biomarkers, is utilized in validation assay for multiplex detection of traumatic brain injury indicative glycan biomarkers, demonstrating straightforward and cost-effective micro- and nanoplatforms for accurate detection.

The annonalide diterpene extracted from Casimirella ampla (Miers) reduces inflammatory and antinociceptive events in general models of inflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: The plants of the genus Casimirella ampla (Miers) (C. ampla) are extensively used in folk medicine. For a long time, rural communities have been using extracts from its roots for food and therapeutic purposes. The extract is rich in diterpenoid annonalide (Annona), which has antiophidic, anti-inflammatory and antinociceptive properties. Inflammation is the body's primary defense mechanism against cell damage and invasion by pathogens, which can trigger acute and chronic inflammatory processes. The first line of treatment for this condition consists of the use of non-steroidal anti-inflammatory drugs, but these have numerous associated collateral damages, based on scientific knowledge about diterpenoids from C. ampla, as well as their already reported antinociceptive and anti-inflammatory properties. AIMS OF THE STUDY: Evaluate the effect of Annona in classic models of inflammation and pain. MATERIALS AND METHODS: Animals were pretreated with Annona (0.1, 1.0 and 10 mg/kg), or Tween 80 (2%), or indomethacin (Indo) (10 mg/kg) orally in the paw edema tests induced by carrageenan (Cg), serotonin (5-HT), histamine, bradykinin, 48/80 and, prostaglandin E2 (PGE2), evaluating microscopic lesion scores, migration of leukocytes to the peritoneal cavity, concentration of myeloperoxide (MPO), malonyldialdehyde (MDA) and glutathione (GSH), abdominal contortion test by acetic acid and formalin test. RESULTS: Treatment with Annona compound at a dose of 0.1 mg/kg was more effective in reducing inflammatory, oxidant and nociceptive parameters, as it reduced paw edema induced by carrageenan, through different mediators and migration of inflammatory cells. Furthermore, it worked by reducing the concentration of MPO, MDA, preserving GSH levels and reducing nociception caused by formalin and acetic acid.

Exploring the antiviral potential of justicidin B and four glycosylated lignans from Phyllanthus brasiliensis against Zika virus: A promising pharmacological approach.

BACKGROUND: Zika virus (ZIKV) is an emerging arbovirus that in recent years has been associated with cases of severe neurological disorders, such as microcephaly in newborns and Guillain-Barré syndrome in adults. As there is no vaccine or treatment, the search for new therapeutic targets is of great relevance. In this sense, plants are extremely rich sources for the discovery of new bioactive compounds and the species Phyllanthus brasiliensis (native to the Amazon region) remains unexplored. PURPOSE: To investigate the potential antiviral activity of compounds isolated from P. brasiliensis leaves against ZIKV infection. METHODS: In vitro antiviral assays were performed with justicidin B (a lignan) and four glycosylated lignans (tuberculatin, phyllanthostatin A, 5-O-ß-d-glucopyranosyljusticidin B, and cleistanthin B) against ZIKV in Vero cells. MTT colorimetric assay was used to assess cell viability and plaque forming unit assay to quantify viral load. In addition, for justicidin B, tests were performed to investigate the mechanism of action (virucidal, adsorption, internalization, post-infection). RESULTS: The isolated compounds showed potent anti-ZIKV activities and high selectivity indexes. Moreover, justicidin B, tuberculatin, and phyllanthostatin A completely reduced the viral load in at least one of the concentrations evaluated. Among them, justicidin B stood out as the main active, and further investigation revealed that justicidin B exerts its antiviral effect during post-infection stages, resulting in a remarkable 99.9 % reduction in viral load when treatment was initiated 24 h after infection. CONCLUSION: Our findings suggest that justicidin B inhibits endosomal internalization and acidification, effectively interrupting the viral multiplication cycle. Therefore, the findings shed light on the promising potential of isolated compounds isolated from P. brasiliensis, especially justicidin B, which could contribute to the drug development and treatments for Zika virus infections.

Frequency of skin diseases in renal transplant recipients and patients with chronic kidney disease in a tertiary center: a cross-sectional study

ABSTRACT BACKGROUND: The prevalence of chronic kidney disease (CKD) has increased in the recent decades, along with the number of patients in the terminal stages of this disease, requiring transplantation. Some skin disorders are more frequent in patients with CKD and in renal transplant recipients (RTR). OBJECTIVES: To evaluate the frequency of skin diseases in RTR and patients with CKD receiving conservative treatment. DESIGN AND SETTING: This observational cross-sectional study recruited consecutive patients with CKD and RTR from a nephrology clinic at a teaching hospital in Brazil between 2015 and 2020. METHODS: Quantitative, descriptive, and analytical approaches were used. The sample was selected based on convenience sampling. Data were collected from dermatological visits and participants' medical records. RESULTS: Overall, 308 participants were included: 206 RTR (66.9%, median age: 48 years, interquartile range [IQR] 38.0-56.0, 63.6% men) and 102 patients with CKD (33.1%, median age: 61.0 years, IQR 50.0-71.2, 48% men). The frequency of infectious skin diseases (39.3% vs. 21.6% P = 0.002) were higher in RTR than in patients with CKD. Neoplastic skin lesions were present in nine (4.4%) RTR and in only one (1.0%) patient with CKD. Among the RTR, the ratio of basal cell carcinoma to squamous cell carcinoma was 2:1. CONCLUSIONS: This study revealed that an increased frequency of infectious skin diseases may be expected in patients who have undergone kidney transplantation. Among skin cancers, BCC is more frequently observed in RTR, especially in those using azathioprine.

Hybrid use of Raman spectroscopy and artificial neural networks to discriminate Mycobacterium bovis BCG and other Mycobacteriales.

Even in the face of the COVID-19 pandemic, Tuberculosis (TB) continues to be a major public health problem and the 2nd biggest infectious cause of death worldwide. There is, therefore, an urgent need to develop effective TB diagnostic methods, which are cheap, portable, sensitive and specific. Raman spectroscopy is a potential spectroscopic technique for this purpose, however, so far, research efforts have focused primarily on the characterisation of Mycobacterium tuberculosis and other Mycobacteria, neglecting bacteria within the microbiome and thus, failing to consider the bigger picture. It is paramount to characterise relevant Mycobacteriales and develop suitable analytical tools to discriminate them from each other. Herein, through the combined use of Raman spectroscopy and the self-optimising Kohonen index network and further multivariate tools, we have successfully undertaken the spectral analysis of Mycobacterium bovis BCG, Corynebacterium glutamicum and Rhodoccocus erythropolis. This has led to development of a useful tool set, which can readily discern spectral differences between these three closely related bacteria as well as generate a unique spectral barcode for each species. Further optimisation and refinement of the developed method will enable its application to other bacteria inhabiting the microbiome and ultimately lead to advanced diagnostic technologies, which can save many lives.

Open access repository-scale propagated nearest neighbor suspect spectral library for untargeted metabolomics.

Despite the increasing availability of tandem mass spectrometry (MS/MS) community spectral libraries for untargeted metabolomics over the past decade, the majority of acquired MS/MS spectra remain uninterpreted. To further aid in interpreting unannotated spectra, we created a nearest neighbor suspect spectral library, consisting of 87,916 annotated MS/MS spectra derived from hundreds of millions of MS/MS spectra originating from published untargeted metabolomics experiments. Entries in this library, or "suspects," were derived from unannotated spectra that could be linked in a molecular network to an annotated spectrum. Annotations were propagated to unknowns based on structural relationships to reference molecules using MS/MS-based spectrum alignment. We demonstrate the broad relevance of the nearest neighbor suspect spectral library through representative examples of propagation-based annotation of acylcarnitines, bacterial and plant natural products, and drug metabolism. Our results also highlight how the library can help to better understand an Alzheimer's brain phenotype. The nearest neighbor suspect spectral library is openly available for download or for data analysis through the GNPS platform to help investigators hypothesize candidate structures for unknown MS/MS spectra in untargeted metabolomics data.

Putative Identification of New Phragmaline-Type Limonoids from the Leaves of Swietenia macrophylla King: A Case Study Using Mass Spectrometry-Based Molecular Networking.

Swietenia macrophylla King is a plant commonly known as Brazilian mahogany. The wood from its stem is highly prized for its exceptional quality, while its leaves are valued for their high content of phragmalin-type limonoids, a subclass of compounds known for their significant biological activities, including antimalarial, antitumor, antiviral, and anti-inflammatory properties. In this context, twelve isolated limonoids from S. macrophylla leaves were employed as standards in mass spectrometry-based molecular networking to unveil new potential mass spectrometry signatures for phragmalin-type limonoids. Consequently, ultra-performance liquid chromatography coupled with high-resolution mass spectrometry was utilized for data acquisition. Subsequently, the obtained data were analyzed using the Global Natural Products Social Molecular Networking platform based on spectral similarity. In summary, this study identified 24 new putative phragmalin-type limonoids for the first time in S. macrophylla. These compounds may prove valuable in guiding future drug development efforts, leveraging the already established biological activities associated with limonoids.

Microbial Metabolites Annotation by Mass Spectrometry-Based Metabolomics.

Since the discovery of penicillin, microbial metabolites have been extensively investigated for drug discovery purposes. In the last decades, microbial derived compounds have gained increasing attention in different fields from pharmacognosy to industry and agriculture. Microbial metabolites in microbiomes present specific functions and can be associated with the maintenance of the natural ecosystems. These metabolites may exhibit a broad range of biological activities of great interest to human purposes. Samples from either microbial isolated cultures or microbiomes consist of complex mixtures of metabolites and their analysis are not a simple process. Mass spectrometry-based metabolomics encompass a set of analytical methods that have brought several improvements to the microbial natural products field. This analytical tool allows the comprehensively detection of metabolites, and therefore, the access of the chemical profile from those biological samples. These analyses generate thousands of mass spectra which is challenging to analyse. In this context, bioinformatic metabolomics tools have been successfully employed to accelerate and facilitate the investigation of specialized microbial metabolites. Herein, we describe metabolomics tools used to provide chemical information for the metabolites, and furthermore, we discuss how they can improve investigation of microbial cultures and interactions.