Assessment of internal exposure risk from metals pollution of occupational and non-occupational populations around a non-ferrous metal smelting plant.

Non-ferrous metal smelting poses significant risks to public health. Specifically, the copper smelting process releases arsenic, a semi-volatile metalloid, which poses an emerging exposure risk to both workers and nearby residents. To comprehensively understand the internal exposure risks of metal(loid)s from copper smelting, we explored eighteen metal(loid)s and arsenic metabolites in the urine of both occupational and non-occupational populations using inductively coupled plasma mass spectrometry with high-performance liquid chromatography and compared their health risks. Results showed that zinc and copper (485.38 and 14.00 µg/L), and arsenic, lead, cadmium, vanadium, tin and antimony (46.80, 6.82, 2.17, 0.40, 0.44 and 0.23 µg/L, respectively) in workers (n=179) were significantly higher compared to controls (n=168), while Zinc, tin and antimony (412.10, 0.51 and 0.15 µg/L, respectively) of residents were significantly higher than controls. Additionally, workers had a higher monomethyl arsenic percentage (MMA%), showing lower arsenic methylation capacity. Source appointment analysis identified arsenic, lead, cadmium, antimony, tin and thallium as co-exposure metal(loid)s from copper smelting, positively relating to the age of workers. The hazard index (HI) of workers exceeded 1.0, while residents and control were approximately at 1.0. Besides, all three populations had accumulated cancer risks exceeding 1.0 × 10-4, and arsenite (AsIII) was the main contributor to the variation of workers and residents. Furthermore, residents living closer to the smelting plant had higher health risks. This study reveals arsenic exposure metabolites and multiple metals as emerging contaminants for copper smelting exposure populations, providing valuable insights for pollution control in non-ferrous metal smelting.

Prostaglandin Metabolites Analysis in Urine by LC-MS/MS.

The analysis of prostaglandin urinary metabolites is valuable for assessing physiological processes and identifying disease biomarkers. These metabolites, derived from the breakdown of prostaglandins, offer a noninvasive means to gauge prostaglandin production and its potential impact on various biological functions. We report an efficient LC-MS method of four commonly analyzed prostaglandin urinary metabolites including tetranor-PGEM (derived from PGE2), tetranor-PGDM, 11ß-PGF2α, and 2,3-dinor-11ß-PGF2α (derived from PGD2). Each metabolite possesses distinct characteristics and clinical applications, collectively contributing to our understanding of prostaglandin-mediated pathways.

Facial synthesis of fluorine-engineered magnetic covalent organic framework for selective and ultrasensitive determination of fipronil, its metabolites and analogs in food samples.

To improve the adsorption affinity and selectivity of fipronils (FPNs), including fipronil, its metabolites and analogs, a magnetic covalent organic framework (Fe3O4@COF-F) with copious fluorine affinity sites was innovatively designed as an adsorbent of magnetic solid-phase extraction (MSPE). The enhanced surface area, pore size, crystallinity of Fe3O4@COF-F and its exponential adsorption capacities (187.3-231.5 mg g-1) towards fipronils were investigated. Combining MSPE with high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), an analytical method was established for the selective determination of fipronils in milk and milk powder samples. This method achieved high sensitivity (LODs: 0.004-0.075 ng g-1), satisfactory repeatability and accuracy with spiked recoveries ranging from 89.9% to 100.3% (RSDs≤5.1%). Overall, the constructed Fe3O4@COF-F displayed great potential for the selective enrichment of fipronils, which could be ascribed to fluorine­fluorine interaction. This method proposed a feasible and promising strategy for the development of functionalized COF and broadened its application in fluorine containing hazards detection.

Influencia de la edad en el contenido de fenoles y ligninas en Gmelina arborea (Lamiaceae) / The influence of age on the phenolic contents and lignins of Gmelina arborea (Lamiaceae)

Resumen Introducción: La melina (Gmelina arborea), es una especie de gran interés por su madera y propiedades medicinales. En Costa Rica, existen clones genéticamente superiores que se propagan sin el conocimiento de la edad ontogénica y fisiológica de los materiales. Objetivo: Evaluar la relación del contenido de fenoles y ligninas en hojas, peciolos, tallos y raíces de plantas con diferentes edades. Métodos: Los contenidos de fenoles y ligninas totales se determinaron mediante el método colorimétrico de Folin-Ciocalteu y el método de extracción alcalina, respectivamente. Para la investigación se eligieron plantas in vitro "año cero" y árboles de año y medio, cuatro, siete y 20 años. El muestreo se realizó en marzo y abril del 2021. Resultados: Se demostró que todas las partes de la planta analizadas contienen compuestos fenólicos y ligninas, independientemente de su edad. No hubo una correlación positiva entre la edad con el contenido de fenoles y ligninas para ninguna condición de desarrollo, pues los valores más altos no se obtuvieron en los árboles más longevos. Los extractos de hojas de las plantas in vitro y los árboles de siete años mostraron, respectivamente, los contenidos más altos de fenoles y ligninas para todas las condiciones (P < 0.05). Los valores promedio más bajos de compuestos fenólicos para todas las condiciones se obtuvieron en los árboles de cuatro años. Respecto a las ligninas, el contenido más bajo se presentó en las raíces más longevas, aunque la tendencia no se mantuvo para el resto de las partes de la planta. Conclusiones: La investigación muestra los primeros resultados del contenido de compuestos fenólicos y ligninas presentes en diferentes tejidos de una especie forestal de edades diferentes. Por lo tanto, son los primeros valores de referencia acerca del compromiso bioquímico para la síntesis fenólica según la edad y el estado de desarrollo específico de una planta leñosa.

Abstract Introduction: Melina (Gmelina arborea) is a tree species of great interest for its wood and medicinal properties. In Costa Rica, there are genetically superior clones that are propagated without knowledge of the ontogenic and physiological age of the materials. Objective: To evaluate how age influences the content of phenols and lignins in leaves, petioles, stems, and roots of melina plants. Methods: The total phenolic and lignins contents were determined using Folin-Ciocalteu colorimetric method and alkaline extraction method, respectively. Plants of five different ages were chosen for the investigation (in vitro plants "year 0" and trees of a year and a half, four, seven and 20 years). Sampling was done in March and April 2021. Results: All parts of the plant analyzed contain phenolic compounds and lignins, regardless of their age. There was no positive correlation between age and phenol and lignin content for any development condition, since the highest values were not obtained in the oldest trees. Leaf extracts from in vitro plants and seven-year-old trees showed, respectively, the highest phenol and lignin contents for all conditions (P < 0.05). The lowest average values of phenolic compounds for all conditions were obtained in four-year-old trees. Regarding lignins, the lowest content occurred in the oldest roots, although the trend was not maintained for the rest of the plant parts. Conclusions: This study provides the first results of the content of phenolic compounds and lignins present in different tissues of a forest species of different ages. Therefore, they are the first reference values about the biochemical commitment for phenolic synthesis according to the age and the specific developmental stage of a woody plant.

Magnetic covalent organic framework as an absorbent coupled with a portable mass spectrometer for rapid detection of malachite green and its metabolite residues.

It is important to develop specific adsorbents for malachite green and other fish drug residues. Herein, a simple strategy for synthesizing a novel magnetic covalent organic frameworks (rFe3O4@Py-COF) has been studied, and the materials were used as a magnetic absorbent for solid phase extraction (MSPE) of malachite green (MG) and its metabolite as leucomalachite green (LMG) in fishes. In this study, the mild reduction program of formic acid replacing traditional sodium borohydride as a reducing agent has been adopted to increase the stability of the framework, which can maintain the original high crystallinity and surface area of the reduced COF. The secondary amine bond is expected to be used as the reaction center for further functionalization of COF pore wall. Subsequently, rFe3O4@Py-COF (rmCOF) obtained after reduction was used as MSPE materials to detect MG and LMG by a portable mass spectrometer. After optimizing the conditions, the linearity is good within the range of 1.25∼100 µg/kg (R2≥0.9954), the limits of detection (LODs) are 0.31∼0.44 µg/kg with satisfactory recovery (85.0 %∼106.0 %). These results indicate that the assay is suitable for monitoring MG and LMG in complex aquatic foods, providing protection for food safety.

The biology and chemistry of a mutualism between a soil bacterium and a mycorrhizal fungus.

Arbuscular mycorrhizal (AM) fungi (e.g., Rhizophagus species) recruit specific bacterial species in their hyphosphere. However, the chemical interplay and the mutual benefit of this intricate partnership have not been investigated yet, especially as it involves bacteria known as strong producers of antifungal compounds such as Bacillus velezensis. Here, we show that the soil-dwelling B. velezensis migrates along the hyphal network of the AM fungus R. irregularis, forming biofilms and inducing cytoplasmic flow in the AM fungus that contributes to host plant root colonization by the bacterium. During hyphosphere colonization, R. irregularis modulates the biosynthesis of specialized metabolites in B. velezensis to ensure stable coexistence and as a mechanism to ward off mycoparasitic fungi and bacteria. These mutual benefits are extended into a tripartite context via the provision of enhanced protection to the host plant through the induction of systemic resistance.

Invisible hazards: Exploring neonicotinoid contamination and its environmental risks in urban parks across China.

Neonicotinoids (NEOs) are commonly used pesticides in agriculture. Urban parks containing numerous green plants and flowers also require NEOs for pest control. However, information on the distribution patterns and environmental risks of NEOs and their metabolites in urban park soils has yet to be discovered, which seriously limits the comprehensive evaluation of the potential hazards of NEOs. Our study explored the occurrence and distribution patterns of ten NEOs and five major metabolites in park soils from Guangzhou, Shijiazhuang, and Urumqi of China. At least three NEOs were detected in 95 % of soil samples, with the sum of all NEOs (∑10NEOs) ranging from 2.21 to 204 ng/g. Guangzhou has the highest levels of ∑10NEOs (median: 52.1 ng/g), followed by Urumqi (49.3 ng/g) and Shijiazhuang (21.7 ng/g). The top three most common NEOs in all three cities are imidacloprid, acetamiprid, and thiacloprid, which together account for 67 % to 70 % of ∑10NEOs. The levels of the metabolites of NEOs show a significant positive correlation with their corresponding parent NEOs. These NEOs pose detrimental effects to non-targeted invertebrates in the soil. Our findings raise concern about the environmental risks posed by NEO exposure to humans and other organisms in urban parks.

Non-invasive monitoring of adrenocortical activity in the Gould's wattled bat (Chalinolobus gouldii).

Although bats are the second most species-rich mammalian order, very little is known about their endocrine physiology. Glucocorticoids (GCs) are commonly associated with the stress response, but also modulate vital physiological functions which help animals adapt to their environment. Understanding normal patterns of adrenocortical activity can provide valuable insights into a species' fitness. Non-invasive hormone monitoring via faecal samples provides an integrated measure of adrenocortical activity while minimising stress on the animal but must be properly validated to ensure reliable results. The goal of this study was to validate an enzyme immunoassay for monitoring faecal glucocorticoid metabolites (FGMs) in a common Australian insectivorous bat species, the Gould's wattled bat (Chalinolobus gouldii). We compared the performance of five assays for monitoring changes in FGMs following capture and transfer of C.gouldii from the wild to captivity. Four of the five assays detected a significant increase in FGMs following capture, but the magnitude of the increase and consistency across individuals differed considerably. We selected the UVM-69a assay as the best performing assay to then describe normative patterns of adrenocortical activity in the species. Males had higher FGM levels than females, and juveniles had higher FGM levels than adults. Individuals with poorer body condition had higher FGM levels. We also demonstrate seasonal patterns of FGMs with higher levels in March and April corresponding with reproductive up-regulation and lower levels in May and November. Our study is the first of its kind to examine adrenocortical activity in an Australian insectivorous bat and provides a valuable tool for studying this species. Understanding adrenal function in common species such as C.gouldii can shed light on the physiological mechanisms facilitating survival and success in changing environments.

Altitudinal variation in rhizosphere microbial communities of the endangered plant Lilium tsingtauense and the environmental factors driving this variation.

The rhizosphere soil properties and microbial communities of Lilium tsingtauense, an endangered wild plant, have not been examined in previous studies. Here, we characterized spatial variation in soil properties and microbial communities in the rhizosphere of L. tsingtauense. We measured the abundance of L. tsingtauense at different altitudes and collected rhizosphere and bulk soils at three representative altitudes. The results showed that L. tsingtauense was more abundant, and the rhizosphere soil was richer in nitrogen, phosphorus, potassium, water content, and organic matter and more acidic at high altitudes than at lower altitudes. The diversity and richness of rhizosphere bacteria and fungi increased with altitude and were higher in rhizosphere soil than in bulk soil. In addition, ectomycorrhizal fungi, endophytic fungi, and nitrogen-fixing bacteria were more abundant, and plant-pathogenic fungi were less abundant at high altitudes. Co-occurrence network analysis identified four key phyla (Bacteroidota, Proteobacteria, Ascomycota, and Basidiomycota) in the microbial communities. We identified a series of microbial taxa (Acidobacteriales, Xanthobacteraceae, and Chaetomiaceae) and rhizosphere soil metabolites (phosphatidylcholine and phosphatidylserine) that are crucial for the survival of L. tsingtauense. Correlation analysis and random forest analysis showed that some environmental factors were closely related to the rhizosphere soil microbial community and played an important role in predicting the distribution and growth status of L. tsingtauense. In sum, the results of this study revealed altitudinal variation in the rhizosphere microbial communities of L. tsingtauense and the factors driving this variation. Our findings also have implications for habitat restoration and the conservation of this species. IMPORTANCE: Our study highlighted the importance of the rhizosphere microbial community of the endangered plant L. tsingtauense. We found that soil pH plays an important role in the survival of L. tsingtauense. Our results demonstrated that a series of microbial taxa (Acidobacteriales, Xanthobacteraceae, Aspergillaceae, and Chaetomiaceae) and soil metabolites (phosphatidylcholine and phosphatidylserine) could be essential indicators for L. tsingtauense habitat. We also found that some environmental factors play an important role in shaping rhizosphere microbial community structure. Collectively, these results provided new insights into the altitudinal distribution of L. tsingtauense and highlight the importance of microbial communities in their growth.

Small molecule modulators of Alpha-Synuclein Aggregation and Toxicity: Pioneering an Emerging Arsenal Against Parkinson's Disease.

Parkinson's disease (PD) is primarily characterized by loss of dopaminergic neurons in the substantia nigra pars compacta region of the brain and accumulation of aggregated forms of alpha-synuclein (α-Syn), an intrinsically disordered protein, in the form of Lewy Bodies and Lewy Neurites. Substantial evidences point to the aggregated/fibrillar forms of α-Syn as a central event in PD pathogenesis, underscoring the modulation of α-Syn aggregation as a promising strategy for PD treatment. Consequently, numerous anti-aggregation agents, spanning from small molecules to polymers, have been scrutinized for their potential to mitigate α-Syn aggregation and its associated toxicity. Among these, small molecule modulators like osmoprotectants, polyphenols, cellular metabolites, metals, and peptides have emerged as promising candidates with significant potential in PD management. This article offers a comprehensive overview of the effects of these small molecule modulators on the aggregation propensity and associated toxicity of α-Syn and its PD-associated mutants. It serves as a valuable resource for identifying and developing potent, non-invasive, non-toxic, and highly specific small molecule-based therapeutic arsenal for combating PD. Additionally, it raises pertinent questions aimed at guiding future research endeavours in the field of α-Syn aggregation remodelling.

Improving the growth and intestinal colonization of Escherichia coli Nissle 1917 by strengthening its oligopeptides importation ability.

Escherichia coli Nissle 1917 (EcN), the probiotic featured with well-established safety in different host, is emerging as a favored chassis for the construction of engineered probiotics for disease treatment. However, limited by the low intestinal colonization ability of EcN, repeated administration is required to maximize the health benefits of the EcN-derived engineered probiotics. Here, using fecal metabolites as "metabolites pool", we developed a metabolomic strategy to characterize the comprehensive metabolic profile of EcN. Compared with Prevotella copri DSM 18205 (P. copri), one of the dominant microbes in gut flora, EcN exhibited minor growth advantage under the fecal metabolites-containing condition for its lower metabolic capability towards fecal metabolites. Further study indicated that EcN lacked the ability to import the oligopeptides containing more than two amino acids. The shortage of oligopeptides-derived amino acids might limit the growth of EcN by restricting its purine metabolism. Assisted with the bioinformatic and qRT-PCR analyses, we identified a tripeptides-specific importer Pc-OPT in P. copri, which was mainly distributed in genera Prevotella and Bacteroides. Overexpression of Pc-OPT improved the tripeptides importation of EcN and promoted its growth and intestinal colonization. Notably, 16S rRNA gene amplicon sequencing results indicated that strengthening the oligopeptides importation ability of EcN might promote its intestinal colonization by adjusting the gut microbial composition. Our study reveals that the growth and intestinal colonization of EcN is limited by its insufficient oligopeptides importation and paves road for promoting the efficacy of the EcN-derived synthetic probiotics by improving their intestinal colonization ability.

Effect of host breeds on gut microbiome and fecal metabolome in commercial pigs.

BACKGROUND: Gut microbial composition and its metabolites are crucial for livestock production performance. Metabolite profiles from autopsied biospecimens provide vital information on the basic mechanisms that affect the overall health and production traits in livestock animals. However, the role of the host breed in the gut microbiome and fecal metabolome of commercial pigs remains unclear. In this work, differences in microbiota composition among three commercial pig breeds Duroc, Yorkshire, and Landrace were measured by 16S rRNA gene sequencing. Fecal metabolite compositions of the three pig breeds were detected using untargeted metabolomics. RESULTS: There were significant differences in the gut microbiomes of the three species, indicating that host breed affects the diversity and structure of gut microbiota. Several breed-associated microorganisms were identified at different taxonomic levels. Notely, most microbial taxa were annotated as Lactobacillacea, Muribaculaceae, and Oscillospiraceae. Several bacteria, including Lactobacillus, Subdoligranulum, Faecalibacterium, Oscillospira, Oscillospiraceae_UCG-002, and Christensenellaceae_R-7_group, could be considered as biomarkers for improving the backfat thickness (BF) for commercial pigs. Additionally, KEGG analysis of gut microbiota further revealed that arginine biosynthesis, pyruvate metabolism, and fatty acid biosynthesis varied greatly among pig breeds. Multiple gut bacterial metabolites (e.g., spermidine, estradiol, and palmitic acid) were identified as breed-associated. Mediation analysis ultimately revealed the cross-talk among gut microbiota, metabolites, and BF thickness, proclaiming that the microbial and metabolic biomarkers identified in this study could be used as biomarkers for improving BF phenotype. CONCLUSIONS: This work provides vital insights into breed effects on gut microbiota and metabolite compositions of commercial pigs and uncovers potential biomarkers that are significant for pig breed improvement.

Comparative study of polysaccharide metabolites in purple, orange, and white Ipomoea batatas tubers.

We employed LC-MS/MS to investigate the metabolic profiles of polysaccharide compounds in white, orange, and purple sweet potato flesh. Comparisons between Orange vs White, Purple vs Orange, and Purple vs White identified 69 polysaccharide metabolites, including 23, 36, and 44 differential metabolites, respectively, with distinct differentiation. Among the three sample groups, 14 polysaccharide compounds and 2 anthocyanins exhibited significant differences. Our further analysis indicated that anthocyanins occupy a central position in the related network diagram and are interconnected with polysaccharides. In metabolic pathways, sucrose and the anthocyanin precursor UDP-glucose were upregulated in purple sweet potatoes, along with elevated levels of pelargonidin 3-O-ß-D-sambubioside and delphinidin 3,5-diglucoside. Conversely, sucrose was downregulated in purple sweet potatoes while increasing in white and orange varieties. Therefore, we hypothesize that the competition between sugars and anthocyanins for shared biosynthesis precursors is attributed to differential polysaccharide metabolites among sweet potato tubers of three colors.

The impact of traditional Chinese medicine and dietary compounds on modulating gut microbiota in hepatic fibrosis: A review.

Traditional Chinese medicine (TCM) and dietary compounds have a profound influence on the regulation of gut microbiota (GM) in hepatic fibrosis (HF). Certain substances found in both food and herbs that are edible and medicinal, such as dietary fiber, polyphenols, and polysaccharides, can generate beneficial metabolites like short-chain fatty acids (SCFAs), bile acids (BAs), and tryptophan (Trp). These compounds contribute to regulate the GM, reduce levels of endotoxins in the liver, and alleviate fibrosis and inflammation in the liver. Furthermore, they enhance the composition and functionality of GM, promoting the growth of beneficial bacteria while inhibiting the proliferation of harmful bacteria. These mechanisms mitigate the inflammatory response in the intestines and maintain the integrity of the intestinal barrier. The purpose of this review is to analyze how the GM regulates the pathogenesis of HF, evaluate the regulatory effect of TCM and dietary compounds on the intestinal microflora, with a particular emphasis on modulating flora structure, enhancing gut barrier function, and addressing associated pathogenic factors, thereby provide new insights for the treatment of HF.

Potential of traditional medicines in alleviating COVID-19 symptoms.

This review discusses the prevention and treatment of coronavirus disease 2019 (COVID-19) caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Mutations in its spike glycoprotein have driven the emergence of variants with high transmissibility and immune escape capabilities. Some antiviral drugs are ineffective against the BA.2 subvariant at the authorized dose. Recently, 150 natural metabolites have been identified as potential candidates for development of new anti-COVID-19 drugs with higher efficacy and lower toxicity than those of existing therapeutic agents. Botanical drug-derived bioactive molecules have shown promise in dampening the COVID-19 cytokine storm and thus preventing pulmonary fibrosis, as they exert a strong binding affinity for viral proteins and inhibit their activity. The Health Ministry of Thailand has approved Andrographis paniculata (Jap. Senshinren) extracts to treat COVID-19. In China, over 85% of patients infected with SARS-CoV-2 receive treatments based on traditional Chinese medicine. A comprehensive map of the stages and pathogenetic mechanisms related to the disease and effective natural products to treat and prevent COVID-19 are presented. Approximately 10% of patients with COVID-19 are affected by long COVID, and COVID-19 infection impairs mitochondrial DNA. As the number of agents to treat COVID-19 is limited, adjuvant botanical drug treatments including vitamin C and E supplementation may reduce COVID-19 symptoms and inhibit progression to long COVID.

Effect of inflammatory cytokines and plasma metabolome on OSA: a bidirectional two- sample Mendelian randomization study and mediation analysis.

Background: Obstructive sleep apnea (OSA) is a common sleep disorder. Inflammatory factors and plasma metabolites are important in assessing its progression. However, the causal relationship between them and OSA remains unclear, hampering early clinical diagnosis and treatment decisions. Methods: We conducted a large-scale study using data from the FinnGen database, with 43,901 cases and 366,484 controls for our discovery MR analysis. We employed 91 plasma proteins from 11 cohorts (totaling 14,824 participants of European descent) as instrumental variables (IVs). Additionally, we conducted a GWAS involving 13,818 cases and 463,035 controls to replicate the MR analysis. We primarily used the IVW method, supplemented by MR Egger, weighted median, simple mode, and weighted mode methods. Meta-analysis was used to synthesize MR findings, followed by tests for heterogeneity, pleiotropy, and sensitivity analysis (LOO). Reverse MR analysis was also performed to explore causal relationships. Results: The meta-analysis showed a correlation between elevated Eotaxin levels and an increased risk of OSA (OR=1.050, 95% CI: 1.008-1.096; p < 0.05). Furthermore, we found that the increased risk of OSA could be attributed to reduced levels of X-11849 and X-24978 (decreases of 7.1% and 8.4%, respectively). Sensitivity analysis results supported the reliability of these findings. Conclusions: In this study, we uncovered a novel biomarker and identified two previously unknown metabolites strongly linked to OSA. These findings underscore the potential significance of inflammatory factors and metabolites in the genetic underpinnings of OSA development and prognosis.

Causal pathways in lymphoid leukemia: the gut microbiota, immune cells, and serum metabolites.

Background: We employed Mendelian randomization (MR) to investigate the causal relationship between the gut microbiota and lymphoid leukemia, further exploring the causal relationships among immune cells, lymphoid leukemia, and potential metabolic mediators. Methods: We utilized data from the largest genome-wide association studies to date, encompassing 418 species of gut microbiota, 713 types of immune cells, and 1,400 serum metabolites as exposures. Summary statistics for lymphoid leukemia, acute lymphocytic leukemia (ALL), and chronic lymphocytic leukemia (CLL) were obtained from the FinnGen database. We performed bidirectional Mendelian analyses to explore the causal relationships among the gut microbiota, immune cells, serum metabolites, and lymphoid leukemia. Additionally, we conducted a two-step mediation analysis to identify potential intermediary metabolites between immune cells and lymphoid leukemia. Results: Several gut microbiota were found to have causal relationships with lymphoid leukemia, ALL, and CLL, particularly within the Firmicutes and Bacteroidetes phyla. In the two-step MR analysis, various steroid hormone metabolites (such as DHEAS, pregnenolone sulfateprogestogen derivatives, and androstenediol-related compounds) were identified as potential intermediary metabolites between lymphoid leukemia and immune cells. In ALL, the causal relationship between 1-palmitoyl-2-docosahexaenoyl-GPE (16:0/22:6) and ALL was mediated by CD62L-plasmacytoid DC%DC (mediated proportion=-2.84%, P=0.020). In CLL, the causal relationship between N6,n6,n6-trimethyllysine and CLL was mediated by HLA DR+ CD8br AC (mediated proportion=4.07%, P=0.021). Conclusion: This MR study provides evidence supporting specific causal relationships between the gut microbiota and lymphoid leukemia, as well as between certain immune cells and lymphoid leukemia with potential intermediary metabolites.

Metabolic mediators: microbial-derived metabolites as key regulators of anti-tumor immunity, immunotherapy, and chemotherapy.

The human microbiome has recently emerged as a focal point in cancer research, specifically in anti-tumor immunity, immunotherapy, and chemotherapy. This review explores microbial-derived metabolites, emphasizing their crucial roles in shaping fundamental aspects of cancer treatment. Metabolites such as short-chain fatty acids (SCFAs), Trimethylamine N-Oxide (TMAO), and Tryptophan Metabolites take the spotlight, underscoring their diverse origins and functions and their profound impact on the host immune system. The focus is on SCFAs' remarkable ability to modulate immune responses, reduce inflammation, and enhance anti-tumor immunity within the intricate tumor microenvironment (TME). The review critically evaluates TMAO, intricately tied to dietary choices and gut microbiota composition, assessing its implications for cancer susceptibility, progression, and immunosuppression. Additionally, the involvement of tryptophan and other amino acid metabolites in shaping immune responses is discussed, highlighting their influence on immune checkpoints, immunosuppression, and immunotherapy effectiveness. The examination extends to their dynamic interaction with chemotherapy, emphasizing the potential of microbial-derived metabolites to alter treatment protocols and optimize outcomes for cancer patients. A comprehensive understanding of their role in cancer therapy is attained by exploring their impacts on drug metabolism, therapeutic responses, and resistance development. In conclusion, this review underscores the pivotal contributions of microbial-derived metabolites in regulating anti-tumor immunity, immunotherapy responses, and chemotherapy outcomes. By illuminating the intricate interactions between these metabolites and cancer therapy, the article enhances our understanding of cancer biology, paving the way for the development of more effective treatment options in the ongoing battle against cancer.

Functional properties and safety traits of L. rhamnosus and L. reuteri postbiotic extracts.

Postbiotics are the non-viable bacterial products or the low molecular weight metabolites produced by probiotics that have received considerable attention owing to their health promoting effects. The present study aimed to investigate the safety and antibacterial properties of postbiotic components of Lacticaseibacillus rhamnosus (Lra) and Limosilactobacillus reuteri (Lre) for their potential applications in food products. The freeze dried postbiotic metabolites (FD-P) from Lra and Lre were extensively analyzed for their physico-chemical properties and antibacterial actions against common food borne pathogens. Higher levels of total flavonoids (1971.79 ± 20 mg Qu/ g), total short-chain fatty acid (23 µg/g), sugar contents, CAT, and SOD anti-oxidative enzymes were detected in the Lra postbiotic, while GSH-px levels and riboflavin were higher in Lre postbiotics (P < 0.01). No significant differences were recorded in the total phenolic (2501 and 2518 mg GAE/ L) and crude protein contents (305. 58 and 296.23 µg/g) of the postbiotics (p ≥ 0.05), respectively. Both FD-P samples showed enhanced activities against Gram-Positive pathogens compared to Gram-Negative pathogens (p < 0.05), while combining the two postbiotics further potentiated the antibacterial actions. Both FD-P samples were non-hemolytic to human erythrocyte cells, and exhibited low cytotoxicity in MRC 5 and IPEC-J2 cell lines at the highest used concentrations (150 mg/ml). In summary, the postbiotics derived from Lra and Lre are safe bioactive ingredients with enhanced antibacterial and antioxidant capabilities, having potential applications as a natural preservatives in food system, potentially enhancing safety and extending the shelf life of food products.

A shift in substrate requirement might cause speciation of the lichenized fungi, Varicellaria hemisphaerica and V. lactea (Pertusariales, Ascomycota).

Proper species recognition is required to correctly estimate species preferences and their vulnerability or for eco-evolutionary inference. Varicellaria hemisphaerica and Varicellaria lactea are almost completely morphologically homogeneous species with unclear identification features. To evaluate the importance of morphological, chemical, and ecological characteristics used in recognition of these species, we tested 670 specimens, of which 42 were analyzed phylogenetically using nucITS rDNA, SSU rDNA, and LSU rDNA markers. This integrated taxonomical approach showed that V. hemisphaerica is distinct from V. lactea, and that substrate requirements, together with phylogenetic differences and the size of soredia, differentiate these species. The chemical composition of secondary lichen metabolites in both analyzed species showed similar variation and, therefore, this feature is not diagnostic in species recognition, although suggested by previous studies. The potential speciation of the two species seems to be caused by the shift in the substrate requirements.