Improving precision management of anxiety disorders: a Mendelian randomization study targeting specific gut microbiota and associated metabolites.

Background: There is growing evidence of associations between the gut microbiota and anxiety disorders, where changes in gut microbiotas may affect brain function and behavior via the microbiota-gut-brain axis. However, population-level studies offering a higher level of evidence for causality are lacking. Our aim was to investigate the specific gut microbiota and associated metabolites that are closely related to anxiety disorders to provide mechanistic insights and novel management perspectives for anxiety disorders. Method: This study used summary-level data from publicly available Genome-Wide Association Studies (GWAS) for 119 bacterial genera and the phenotype "All anxiety disorders" to reveal the causal effects of gut microbiota on anxiety disorders and identify specific bacterial genera associated with anxiety disorders. A two-sample, bidirectional Mendelian randomization (MR) design was deployed, followed by comprehensive sensitivity analyses to validate the robustness of results. We further conducted multivariable MR (MVMR) analysis to investigate the potential impact of neurotransmitter-associated metabolites, bacteria-associated dietary patterns, drug use or alcohol consumption, and lifestyle factors such as smoking and physical activity on the observed associations. Results: Bidirectional MR analysis identified three bacterial genera causally related to anxiety disorders: the genus Eubacterium nodatum group and genus Ruminococcaceae UCG011 were protective, while the genus Ruminococcaceae UCG011 was associated with an increased risk of anxiety disorders. Further MVMR suggested that a metabolite-dependent mechanism, primarily driven by tryptophan, tyrosine, phenylalanine, glycine and cortisol, which is consistent with previous research findings, probably played a significant role in mediating the effects of these bacterial genera to anxiety disorders. Furthermore, modifying dietary pattern such as salt, sugar and processed meat intake, and adjusting smoking state and physical activity levels, appears to be the effective approaches for targeting specific gut microbiota to manage anxiety disorders. Conclusion: Our findings offer potential avenues for developing precise and effective management approaches for anxiety disorders by targeting specific gut microbiota and associated metabolites.

Quantitative health risk assessment of microbial hazards from water sources for community and self-supply drinking water systems.

In low and medium income countries (LMIC) drinking water sources (wells and boreholes) often contain a high number of pathogenic microorganisms, that can pose significant human and environmental health risks. In this study, a quantitative microbial risk assessment approach based on existing literature was conducted to evaluate and compare the quantitative health risks associated with different age groups using various drinking water supply systems. Results showed that both community-supply and self-supply modes exhibit similar levels of risk. However, the self-supply water source consistently showed higher risks compared to the community-supply one. Borehole water was found to be a more suitable option than well water, consistently showing between 5 and 8 lower health risks for E. coli and fecal coliform levels, respectively. The sensitivity analysis further showed the importance of prioritizing the reduction of E. coli concentration in well water and fecal coliform concentration in borehole water. This study offers a fresh perception on quantifying the impact of exposure concentration and age groups, shedding light on how they affect environmental health risks. These findings provide valuable insights for stakeholders involved in the management and protection of water sources.

ESCRT-dependent control of craniofacial morphogenesis with concomitant perturbation of NOTCH signaling.

Craniofacial development is orchestrated by transcription factor-driven regulatory networks, epigenetic modifications, and signaling pathways. Signaling molecules and their receptors rely on endo-lysosomal trafficking to prevent accumulation on the plasma membrane. ESCRT (Endosomal Sorting Complexes Required for Transport) machinery is recruited to endosomal membranes enabling degradation of such endosomal cargoes. Studies in vitro and in invertebrate models established the requirements of the ESCRT machinery in membrane remodeling, endosomal trafficking, and lysosomal degradation of activated membrane receptors. However, investigations during vertebrate development have been scarce. By ENU-induced mutagenesis, we isolated a mouse line, Vps25ENU/ENU, carrying a hypomorphic allele of the ESCRT-II component Vps25, with craniofacial anomalies resembling features of human congenital syndromes. Here, we assessed the spatiotemporal dynamics of Vps25 and additional ESCRT-encoding genes during murine development. We show that these genes are ubiquitously expressed although enriched in discrete domains of the craniofacial complex, heart, and limbs. ESCRT-encoding genes, including Vps25, are expressed in both cranial neural crest-derived mesenchyme and epithelium. Unlike constitutive ESCRT mutants, Vps25ENU/ENU embryos display late lethality. They exhibit hypoplastic lower jaw, stunted snout, dysmorphic ear pinnae, and secondary palate clefting. Thus, we provide the first evidence for critical roles of ESCRT-II in craniofacial morphogenesis and report perturbation of NOTCH signaling in craniofacial domains of Vps25ENU/ENU embryos. Given the known roles of NOTCH signaling in the developing cranium, and notably the lower jaw, we propose that the NOTCH pathway partly mediates the craniofacial defects of Vps25ENU/ENU mouse embryos.

The Transporter Classification Database (TCDB): 2021 update.

The Transporter Classification Database (TCDB; tcdb.org) is a freely accessible reference resource, which provides functional, structural, mechanistic, medical and biotechnological information about transporters from organisms of all types. TCDB is the only transport protein classification database adopted by the International Union of Biochemistry and Molecular Biology (IUBMB) and now (October 1, 2020) consists of 20 653 proteins classified in 15 528 non-redundant transport systems with 1567 tabulated 3D structures, 18 336 reference citations describing 1536 transporter families, of which 26% are members of 82 recognized superfamilies. Overall, this is an increase of over 50% since the last published update of the database in 2016. This comprehensive update of the database contents and features include (i) adoption of a chemical ontology for substrates of transporters, (ii) inclusion of new superfamilies, (iii) a domain-based characterization of transporter families for the identification of new members as well as functional and evolutionary relationships between families, (iv) development of novel software to facilitate curation and use of the database, (v) addition of new subclasses of transport systems including 11 novel types of channels and 3 types of group translocators and (vi) the inclusion of many man-made (artificial) transmembrane pores/channels and carriers.

Nanoparticles of magnetite anchored onto few-layer graphene: A highly efficient Fenton-like nanocomposite catalyst.

Developing a catalyst with high efficiency and recyclability is an important issue for the heterogeneous Fenton-like systems. In this study, magnetic Fe3O4 and reduced graphene oxide (RGO) nanocomposites were prepared by a facile alkaline-thermal precipitation method and employed as a highly effective heterogeneous Fenton-like catalyst for methyl orange (MO) degradation. Characterization of these nanocomposites by XRD, FTIR, Raman, FESEM and TEM revealed that nanoparticles (NPs) of Fe3O4 were tightly anchored on the few-layer RGO sheets. The anchoring of Fe3O4 NPs and the reduction of GO were achieved in one pot without adding any other reducing agents. Based on the measurements of GO surface Zeta potentials, a possible anchoring mechanism of Fe3O4 NPs onto RGO sheets was given. The Fe3O4/RGO nanocomposites exhibited much higher Fenton-like catalytic efficiency for MO degradation than pure Fe3O4 NPs. This degradation process followed the first-order kinetics model, where k1 and T complied with the Arrhenius equation with Ea of 12.79 kJ/mol and A of 8.20 s-1. Magnetic measurements revealed that Fe3O4/RGO nanocomposites were ferromagnetic as indicated by the presence of magnetic hysteresis loops. The Fe3O4/RGO nanocomposites showed good stability and recyclability. Hydroxyl radicals, OH were determined as the dominant oxidative species in Fe3O4/RGO-H2O2 system and the Fenton-like mechanism for MO degradation in water was proposed and discussed.

Process optimization on methyl orange discoloration in Fe3O4/RGO-H2O2 Fenton-like system.

The development of a catalyst with high catalytic activity was one of the most important issues for the heterogeneous Fenton-like process. In this study, nanocomposites of Fe3O4 anchored onto reduced graphene oxide (RGO) were prepared by a moderate alkaline-thermal precipitation method and developed as highly efficient heterogeneous Fenton-like catalysts. The characterization results indicated that Fe3O4 nanoparticles (NPs) were tightly anchored onto few-layer RGO sheets via a strong interaction. Contrast experiments showed that Fe3O4/RGO nanocomposites had much better Fenton-like catalytic activity than Fe3O4 NPs. The process optimization of methyl orange (MO) discoloration in Fe3O4/RGO-H2O2 system was accomplished by central composite design under response surface methodology. A second-order polynomial model was established to predict the optimal values of MO discoloration and its significance was evaluated by analysis of variance. Three-dimensional response surfaces for the interaction between two variables were constructed. Based on the model prediction, the optimum conditions for MO discoloration in Fe3O4/RGO-H2O2 system were 2.9 for solution pH, 16.5 mM H2O2 concentration, 2.5 g/L catalyst dosage and 33.5 min of reaction time, with the maximum predicted value for MO discoloration ratio of 99.98%.