Characteristics and potential clinical applications of the extracellular vesicles of human pathogenic Fungi.

Extracellular vesicles (EVs) are a heterogeneous group of lipid membrane-enclosed compartments that contain different biomolecules and are released by almost all living cells, including fungal genera. Fungal EVs contain multiple bioactive components that perform various biological functions, such as stimulation of the host immune system, transport of virulence factors, induction of biofilm formation, and mediation of host-pathogen interactions. In this review, we summarize the current knowledge on EVs of human pathogenic fungi, mainly focusing on their biogenesis, composition, and biological effects. We also discuss the potential markers and therapeutic applications of fungal EVs.

Impedance Study of Temperature-Stable Relaxor Dielectrics in the System of BCT-BMT Ceramics.

Preparation of a lead-free system (Ba0.8Ca0.2)TiO3-xBi(Mg0.5Ti0.5)O3 (BCT-BMT) with x = 0, 0.1, 0.2, 0.3, 0.4, and 0.5 was carried out using a solid-state reaction technique. X-ray (XRD) diffraction analysis confirmed a tetragonal structure for x = 0, which shifted to cubic (pseudocubic) at x ≥ 0.1. From Rietveld refinement, a single phase with a tetragonal symmetry model (P4mm) was observed for x = 0, and however, for sample x = 0.1 and sample x = 0.5, the data are modeled to cubic (Pm3m). Composition x = 0 showed a prominent Curie peak, typical of ordinary ferroelectrics with a Curie temperature (Tc) ∼130 °C, modified to a typical relaxor dielectric at x ≥ 0.1. However, samples at x = 0.2-0.5 displayed a single semicircle attributed to the bulk response of the material, whereas a slightly depressed second arc appeared for x = 0.5 at 600 °C, indicating a slight contribution to the electrical properties, ascribed to the grain boundary of the material. Finally, the dc resistivity increased with the increase of the BMT content and the solid solution increased the activation energy from 0.58 eV at x = 0 to 0.99 eV for x = 0.5. Adding the BMT content eliminated the ferroelectric behavior at compositions x ≥ 0.1 and led to a linear dielectric response and electrostrictive behavior with a maximum strain of 0.12% for x = 0.2.

Investigation of Dielectric, Ferroelectric, and Strain Responses of (1 - x)[0.90(Bi0.5Na0.5)TiO3 - 0.10SrTiO3] - xCuO Ceramics.

The low-temperature sintering of (Bi0.5Na0.5)TiO3-based ceramics can be achieved by sintering aid CuO. Piezoelectric ceramics (1 - x)[0.90(Bi0.5Na0.5)TiO3 - 0.10SrTiO3] - xCuO (BNT-ST-Cu) with x = 0, 0.01, 0.02, 0.03, and 0.04 were prepared through the mixed oxide route. A tetragonal structure was indexed for the undoped sample. Its structure was found to be changed to a pseudocubic when Cu was added. For undoped Cu samples, the sintering temperature (T s) for sufficient densification was 1160 °C. However, T s was reduced to 1090-1120 °C for Cu-added specimens. Field emission scanning electron microscopy (FE-SEM) showed a uniform and dense grain morphology for all samples. The maximum dielectric constant temperature (T m) was decreased with the doping concentration of Cu and applied frequency. The strain was increased with Cu concentration and had the maximum value of 500 pm/V for the sample x = 0.02 with symmetric and slim strain loops.

Novel homozygous variant in the TPO gene associated with congenital hypothyroidism and mild-intellectual disability.

Congenital hypothyroidism (CH) is one of the most common hereditary disorders affecting neonates worldwide. CH is a multifactorial complex disorder and can be caused by either environmental factors or genetic factors. We studied one Pakistani family with segregating mutations in CH inherited in an autosomal recessive manner. Using whole-exome sequencing (WES), we found a novel homozygous missense variant (c.2315A>G; p.Tyr772Cys) in the thyroid peroxidase (TPO) gene. Different bioinformatics prediction tools and Sanger sequencing were performed to verify the identified variant. Our findings highlight the importance of this gene in causing CH and mild-intellectual disability (ID) in two affected brothers. WES is a convenient and useful tool for the clinical diagnosis of CH and other associated disorders.

Two Cases of Recessive Intellectual Disability Caused by NDST1 and METTL23 Variants.

Intellectual disability (ID) is a highly heterogeneous genetic condition with more than a thousand genes described so far. By exome sequencing of two consanguineous families presenting hallmark features of ID, we identified two homozygous variants in two genes previously associated with autosomal recessive ID: NDST1 (c.1966G>A; p.Asp656Asn) and METTL23 (c.310T>C; p.Phe104Leu). The segregation of the variants was validated by Sanger sequencing in all family members. In silico homology modeling of wild-type and mutated proteins revealed substantial changes in the secondary structure of both proteins, indicating a possible effect on function. The identification and validation of new pathogenic NDST1 and METTL23 variants in two cases of autosomal recessive ID further highlight the importance of these genes in proper brain function and development.

Extracellular Vesicles Derived From Talaromyces marneffei Yeasts Mediate Inflammatory Response in Macrophage Cells by Bioactive Protein Components.

Extracellular vesicles (EVs) loaded with proteins, nucleic acids, membrane lipids, and other virulence factors could participate in pathogenic processes in some fungi such as Cryptococcus neoformans and Candida albicans. However, the specific characteristics of EVs derived from Talaromyces marneffei (TM) still have not been figured out yet. In the present study, it has been observed that TM-derived EVs were a heterogeneous group of nanosized membrane vesicles (30-300 nm) under nanoparticle tracking analysis and transmission electron microscopy. The DiI-labeled EVs could be taken up by RAW 264.7 macrophage cells. Incubation of EVs with macrophages would result in increased expression levels of reactive oxygen species, nitric oxide, and some inflammatory factors including interleukin-1ß, interleukin-6, interleukin-10, and tumor necrosis factor. Furthermore, the expression of co-stimulatory molecules (CD80, CD86, and MHC-II) was also increased in macrophages stimulated with EVs. The level of inflammatory factors secreted by macrophages showed a significant decrease when EVs were hydrolyzed by protease, while that of DNA and RNA hydrolase treatment remained unchanged. Subsequently, some virulence factors in EVs including heat shock protein, mannoprotein 1, and peroxidase were determined by liquid chromatography-tandem mass spectrometry. Taken together, our results indicated that the TM-derived EVs could mediate inflammatory response and its protein would play a key role in regulating the function of RAW 264.7 macrophage cells.