Proteome overview of exosome derived from plasma of cows infected with Mycobacterium bovis.

Bovine tuberculosis (bTB), primarily caused by Mycobacterium bovis (M. bovis), is a globally zoonotic disease with significant economic impacts. Plasma exosomes have been extensively used for investigating disease processes and exploring biomarkers. While mass spectrometry (MS)-based proteomic analysis of plasma exosomes has been employed for human tuberculosis (TB) studies, it has not yet been applied to bTB. Therefore, a comprehensive proteomic overview of plasma exosomes from M. bovis-infected cows is essential. In this study, we presented an extensive proteomic analysis of plasma exosomes from 89 M. bovis-infected cows across three farms, using data dependent acquisition (DDA) mode. Our analysis encompasses 239,894 spectra, 6,011 peptides and 835 proteins. The proteomic overview revealed both consistencies and differences among individual cows, supplements 595 proteins to the bovine exosome library, and enriches tuberculosis and related pathways. Additionally, six pathways were validated as immune response pathways, and three proteins (CATHL1, H1-1, and LCN2) were identified as potential indicators of bTB. This study is the first to investigate the exosome proteome of plasma from cows infected with M. bovis, providing a valuable dataset for exploring candidate bTB markers and understanding the mechanisms of host defense against M. bovis.

Malignant transformation of white sponge nevus: a case report of a novel keratin 4 mutation.

BACKGROUND: White Sponge Nevus (WSN) is traditionally considered a benign genetic disorder affecting the oral mucosa, primarily caused by pathogenic mutations in keratin 4 (KRT4) or keratin 13 (KRT13). Despite its benign nature, recent evidence has begun to question the malignant potential of WSN. CASE PRESENTATION: We report a case involving a 70-year-old man who presented with a white lesion on the right floor of his mouth. Initial diagnostic evaluations confirmed the lesion as WSN. Over a one-year follow-up, the lesion underwent malignant transformation, evolving into local epithelial moderate-to-severe dysplasia. Exome sequencing identified a novel insertion mutation in exon 1 of the KRT4 gene, resulting in a deletion-insertion amino acid mutation involving glycine. Single-cell RNA sequencing further revealed altered epithelial proliferation and differentiation dynamics within the lesion. CONCLUSIONS: This case not only expands the known genetic spectrum of KRT4 mutations associated with WSN but also provides preliminary evidence suggesting the malignant potential of WSN. The novel pathogenic mutation in KRT4 is postulated to alter epithelial proliferation and differentiation, thereby raising concerns about the malignant transformation of WSN. Further studies are warranted to confirm these findings.

Collision-attachment simulation of membrane fouling by oppositely and similarly charged colloids.

The fouling propensity of oppositely charged colloids (OCC) and similarly charged colloids (SCC) on reverse osmosis (RO) and nanofiltration (NF) membranes are systematically investigated using a developed collision-attachment approach. The probability of successful colloidal attachment (i.e., attachment efficiency) is modelled by Boltzmann energy distribution, which captures the critical roles of colloid-colloid/membrane interaction and permeate drag. Our simulations highlight the important effects of ionic strength Is, colloidal size dp and initial flux J0 on combined fouling. In a moderate condition (e.g., Is =10 mM, dp=50 nm and J0= 100 L/m2h), OCC mixtures shows more severe fouling compared to the respective single foulant owing to electrostatic neutralization. In contrast, the flux loss of SCC species falls between those of the two single foulants but more closely resembles that of the single low-charged colloids due to its weak electrostatic repulsion. Increased ionic strength Is leads to less severe fouling for OCC but more severe fouling for SCC, as a result of the suppressed electrostatic attraction/repulsion. At a high Is (e.g., 3-5 M), all the single and mixed systems show the identical pseudo-stable flux Js. Small colloidal size leads to the drag-controlled condition, where severe fouling occurs for both single and mixed foulants. On the contrary, better flux stability appears at greater dp for both individual and mixed species, thanks to the increasingly dominated role of energy barrier and thus lowered attachment efficiency. Furthermore, higher J0 above limiting flux exerts greater permeate drag, leading to elevated attachment efficiency, and thus more flux losses for both OCC and SCC. Our modelling gains deep insights into the role of energy barrier, permeate drag, and attachment efficiency in governing combined fouling, which provides crucial guidelines for fouling reduction in practical engineering.

iTRAQ-based proteomic analysis of Deinococcus radiodurans in response to 12C6+ heavy ion irradiation.

BACKGROUND: Deinococcus radiodurans (D. radiodurans) is best known for its extreme resistance to diverse environmental stress factors, including ionizing radiation (IR), ultraviolet (UV) irradiation, oxidative stress, and high temperatures. Robust DNA repair system and antioxidant system have been demonstrated to contribute to extreme resistance in D. radiodurans. However, practically all studies on the mechanism underlying D. radiodurans's extraordinary resistance relied on the treated strain during the post-treatment recovery lag phase to identify the key elements involved. The direct gene or protein changes of D. radiodurans after stress have not yet been characterized. RESULTS: In this study, we performed a proteomics profiling on D. radiodurans right after the heavy ion irradiation treatment, to discover the altered proteins that were quickly responsive to IR in D. radiodurans. Our study found that D. radiodurans shown exceptional resistance to 12C6+ heavy ion irradiation, in contrast to Escherichia coli (E.coli) strains. By using iTRAQ (Isobaric Tags for Relative and Absolute Quantitation)-based quantitative mass spectrometry analysis, the kinetics of proteome changes induced by various dosages of 12C6+ heavy ion irradiation were mapped. The results revealed that 452 proteins were differentially expressed under heavy ion irradiation, with the majority of proteins being upregulated, indicating the upregulation of functional categories of translation, TCA cycle (Tricarboxylic Acid cycle), and antioxidation regulation under heavy ion irradiation. CONCLUSIONS: This study shows how D. radiodurans reacts to exposure to 12C6+ heavy ion irradiation in terms of its overall protein expression profile. Most importantly, comparing the proteome profiling of D. radiodurans directly after heavy ion irradiation with research on the post-irradiation recovery phase would potentially provide a better understanding of mechanisms underlying the extreme radioresistance in D. radiodurans.

Association of Hashimoto's thyroiditis and anti-thyroid antibodies with oral lichen planus: A cross-sectional study.

Hashimoto's thyroiditis (HT) and its autoantibodies may be associated with oral lichen planus (OLP). In this cross-sectional study, we aimed to assess the relationship among HT, auto-anti-thyroid antibodies, and OLP in a Chinese population of 247 patients with oral lichen planus. Clinical manifestations of OLP were evaluated using the Thongprasom scoring system and clinical type. The diagnosis of HT was based on thyroid function, anti-thyroid peroxidase antibody (anti-TPOAb) and anti-thyroglobulin antibody (anti-TgAb) detection, and ultrasonography. The prevalence of HT in all patients with OLP was 39.68% (98/247); the prevalence in females with OLP was 46.24% (86/186), which was higher than that in males with OLP 19.67% (12/61) (P < 0.01). The titers of the two HT autoantibodies in females with OLP were higher than those in males (P < 0.01). The clinical manifestations of OLP, regardless of being evaluated using the Thongprasom system or clinical type, were not significantly associated with HT development or TPOAb (P = 0.864) or TgAb titers (P = 0.745). In this population-based southern Chinese cohort, the prevalence of HT in patients with OLP, particularly in female patients with OLP, was significantly higher than that in the general population. Female patients had higher HT autoantibody titers than male patients. However, the clinical manifestations of OLP were not significantly correlated with either HT development or auto-anti-thyroid antibody levels. The findings could help further elucidate the factors involved in the relationship between oral lichen planus and Hashimoto's thyroiditis.

Role of biologics in refractory recurrent aphthous stomatitis.

Refractory recurrent aphthous stomatitis (RRAS) manifests as severe ulcerative lesions of the oral mucosa with poor healing and a poor response to conventional therapy, with or without systemic diseases. Its treatment remains a clinical challenge owing to the lack of effective therapies. Recently, biologics have emerged as promising targeted therapies for RRAS. The biologics targeting specific inflammatory pathways involved in the pathogenesis of RRAS, including tumor necrosis factor-alpha inhibitors and interleukin inhibitors, offer a more precise and promising therapeutic approach for RRAS. These targeted therapies have been shown to promote healing and decrease recurrence frequency in, and improve the quality of life of patients with RRAS. Herein, the types and mechanisms of biologics currently used to treat RRAS have been reviewed; furthermore, the dose, duration, therapeutic efficacy, and adverse effects of RRAS with or without certain associated systemic diseases, and the current problems and future directions have been discussed.

Epigenetic regulation of ion channels in the sense of taste.

There are five fundamental tastes discovered so far: sweet, bitter, umami, sour and salty. Taste is mediated by the specialized neuroepithelial cells mainly located at the tongue papillae, namely taste receptor cells, which can be classified into type I, type II, type III and type IV. Ion channels are necessary for diverse cell physiological activities including taste sensing, smell experience and temperature perception. Existing evidences have demonstrated distinct structures and working models of ion channels. Epigenetic modifications regulate gene expression mainly through histone modifications, DNA methylation and non-coding RNA-mediated regulation, without altering DNA sequence. This review summarizes how ion channels work during the transduction of multiple tastes, as well as the recent progressions in the epigenetic regulation of ion channels.

A Quantitative Proteomics Study of Early Heat-Regulated Proteins by Two-Dimensional Difference Gel Electrophoresis Identified OsUBP21 as a Negative Regulator of Heat Stress Responses in Rice.

To understand the early heat shock (HS)-regulated cellular responses that influence the tolerance of rice plant to high environmental temperatures, two-dimensional difference gel electrophoresis (2D-DIGE) is performed to explore the early HS-regulated proteome. Multiple proteins that show abundance changes after 1 and 5 min of HS treatment are identified. Of the early HS-regulated proteins identified, the abundance of a ubiquitin-specific protease, OsUBP21, and its Arabidopsis homolog, AtUBP13, is found to be upregulated by 5 min of HS treatment. Further, knocking the expression of OsUBP21 or AtUBP13 down or out increases the tolerance of rice and Arabidopsis plants to HS stress, suggesting that the function of these ubiquitin-specific proteases in regulating plant HS responses is conserved between monocots and dicots. 2D-DIGE showed a group of proteins are differentially regulated in wild-type and ubp21 mutant after 30 min of HS treatment. Among these proteins, 11 are found to interact directly with OsUBP21; thus, they may be targets of OsUBP21. Future analyses of the roles of these OsUBP21-interacting proteins in plant HS responses will help reveal the protein ubiquitination/deubiquitination-regulated cellular responses induced by HS in rice.