A patient-based iPSC-derived hepatocyte model of alcohol-associated cirrhosis reveals bioenergetic insights into disease pathogenesis.

Only ~20% of heavy drinkers develop alcohol cirrhosis (AC). While differences in metabolism, inflammation, signaling, microbiome signatures and genetic variations have been tied to the pathogenesis of AC, the key underlying mechanisms for this interindividual variability, remain to be fully elucidated. Induced pluripotent stem cell-derived hepatocytes (iHLCs) from patients with AC and healthy controls differ transcriptomically, bioenergetically and histologically. They include a greater number of lipid droplets (LDs) and LD-associated mitochondria compared to control cells. These pre-pathologic indicators are effectively reversed by Aramchol, an inhibitor of stearoyl-CoA desaturase. Bioenergetically, AC iHLCs have lower spare capacity, slower ATP production and their mitochondrial fuel flexibility towards fatty acids and glutamate is weakened. MARC1 and PNPLA3, genes implicated by GWAS in alcohol cirrhosis, show to correlate with lipid droplet-associated and mitochondria-mediated oxidative damage in AC iHLCs. Knockdown of PNPLA3 expression exacerbates mitochondrial deficits and leads to lipid droplets alterations. These findings suggest that differences in mitochondrial bioenergetics and lipid droplet formation are intrinsic to AC hepatocytes and can play a role in its pathogenesis.

LipidSig 2.0: integrating lipid characteristic insights into advanced lipidomics data analysis.

In the field of lipidomics, where the complexity of lipid structures and functions presents significant analytical challenges, LipidSig stands out as the first web-based platform providing integrated, comprehensive analysis for efficient data mining of lipidomic datasets. The upgraded LipidSig 2.0 (https://lipidsig.bioinfomics.org/) simplifies the process and empowers researchers to decipher the complex nature of lipids and link lipidomic data to specific characteristics and biological contexts. This tool markedly enhances the efficiency and depth of lipidomic research by autonomously identifying lipid species and assigning 29 comprehensive characteristics upon data entry. LipidSig 2.0 accommodates 24 data processing methods, streamlining diverse lipidomic datasets. The tool's expertise in automating intricate analytical processes, including data preprocessing, lipid ID annotation, differential expression, enrichment analysis, and network analysis, allows researchers to profoundly investigate lipid properties and their biological implications. Additional innovative features, such as the 'Network' function, offer a system biology perspective on lipid interactions, and the 'Multiple Group' analysis aids in examining complex experimental designs. With its comprehensive suite of features for analyzing and visualizing lipid properties, LipidSig 2.0 positions itself as an indispensable tool for advanced lipidomics research, paving the way for new insights into the role of lipids in cellular processes and disease development.

Calcified apoptotic vesicles from PROCR+ fibroblasts initiate heterotopic ossification.

Heterotopic ossification (HO) comprises the abnormal formation of ectopic bone in extraskeletal soft tissue. The factors that initiate HO remain elusive. Herein, we found that calcified apoptotic vesicles (apoVs) led to increased calcification and stiffness of tendon extracellular matrix (ECM), which initiated M2 macrophage polarization and HO progression. Specifically, single-cell transcriptome analyses of different stages of HO revealed that calcified apoVs were primarily secreted by a PROCR+ fibroblast population. In addition, calcified apoVs enriched calcium by annexin channels, absorbed to collagen I via electrostatic interaction, and aggregated to produce calcifying nodules in the ECM, leading to tendon calcification and stiffening. More importantly, apoV-releasing inhibition or macrophage deletion both successfully reversed HO development. Thus, we are the first to identify calcified apoVs from PROCR+ fibroblasts as the initiating factor of HO, and might serve as the therapeutic target for inhibiting pathological calcification.

Molecular phylogeny and morphology of Sporodiniella sinensis sp. nov. (Syzygitaceae, Mucorales), an invertebrate-associated species from Yunnan, China.

During investigations of invertebrate-associated fungi in Yunnan Province of China, a new species, Sporodiniella sinensis sp. nov., was collected. Morphologically, S. sinensis is similar to Sporodiniella umbellata; however, it is distinguished from S. umbellata by its greater number of sporangiophore branches, longer sporangiophores, larger sporangiospores, and columellae. The novel species exhibits similarities of 91.62 % for internal transcribed spacer (ITS), 98.66-99.10 % for ribosomal small subunit (nrSSU), and 96.36-98.22 % for ribosomal large subunit (nrLSU) sequences, respectively, compared to S. umbellata. Furthermore, phylogenetic analyses based on combined sequences of ITS, nrLSU and nrSSU show that it forms a separate clade in Sporodiniella, and clusters closely with S. umbellata with high statistical support. The phylogenetic and morphological evidence support S. sinensis as a distinct species. Here, it is formally described and illustrated, and compared with other relatives.

Metabolic profiling of synovial fluid in human temporomandibular joint osteoarthritis.

Introduction: Temporomandibular joint (TMJ) osteoarthritis (OA) is a common TMJ degenerative disease with an unclear mechanism. Synovial fluid (SF), an important component of TMJ, contains various proteins and metabolites that may directly contribute to OA. The present study aimed to investigate the influence of SF in TMJOA at the metabolite level. Methods: Untargeted and widely targeted metabolic profiling were employed to identify metabolic changes in SF of 90 patients with different TMJOA grades according to TMJ magnetic resonance imaging. Results: A total 1498 metabolites were detected. Most of the metabolites were amino acids and associated metabolites, benzene and substituted derivatives, and lipids. Among patients with mild, moderate and severe TMJOA, 164 gradually increasing and 176 gradually decreasing metabolites were identified, indicating that biosynthesis of cofactors, choline metabolism, mineral absorption and selenocompound metabolism are closely related to TMJOA grade. Combined metabolomics and clinical examination revealed 37 upregulated metabolites and 16 downregulated metabolites in patients with pain, of which 19 and 26 metabolites were positively and negatively correlated, respectively, with maximum interincisal opening. A model was constructed to diagnose TMJOA grade and nine biomarkers were identified. The identified metabolites are key to exploring the mechanism of TMJOA. Discussion: In the present study, a metabolic profile was constructed and assessed using a much larger number of human SF samples from patients with TMJOA, and a model was established to contribute to the diagnosis of TMJOA grade. The findings expand our knowledge of metabolites in human SF of TMJOA patients, and provide an important basis for further research on the pathogenesis and treatment of TMJOA.

Molecular phylogeny and morphology reveal two new entomopathogenic species of Ophiocordyceps (Ophiocordycipitaceae, Hypocreales) parasitic on termites from China.

Two new termite-pathogenic species, Ophiocordycepsglobiperitheciata and O.longistipes, are described from Yunnan Province, China. Six-locus (ITS, nrSSU, nrLSU, tef-1α, rpb1 and rpb2) phylogenetic analyses in combination with morphological observations were employed to characterize these two species. Phylogenetically, O.globiperitheciata is most closely related to Hirsutellacryptosclerotium and O.communis, whereas O.longistipes shares a sister relationship with O.fusiformis. However, O.globiperitheciata differs from H.cryptosclerotium by parasitizing Blattodea and producing clavate, unbifurcated stromata. Ophiocordycepsglobiperitheciata is distinguished from O.communis by multiple stromata, shorter asci and ascospores. Ophiocordycepslongistipes differs from O.fusiformis in producing larger stromata, perithecia, asci and ascospores, as well as smaller citriform or oval conidia. Morphological descriptions of the two new species and a dichotomous key to the 19 termite-pathogenic Ophiocordyceps species are presented.

Correction: Enhancing Specific-Antibody Production to the ragB Vaccine with GITRL That Expand Tfh, IFN-γ+ T Cells and Attenuates Porphyromonas gingivalis Infection in Mice.

[This corrects the article DOI: 10.1371/journal.pone.0059604.].

Postoperative Bisphosphonates Use is Associated with Reduced Adverse Outcomes After Primary Total Joint Arthroplasty of Hip and Knee: A Nationwide Population-Based Cohort Study.

Bisphosphonates have been associated with a decreased risk of revision surgery after total joint arthroplasty of the hip or knee (TJA) because of their effects on decreased periprosthetic bone loss and prosthetic migration. However, the results in the early literature are inconsistent, and the influence of bisphosphonates on associated complications and subsequent TJA remains unknown. This study investigated the association between the use of bisphosphonates and the risk of adverse outcomes after primary TJA. This matched cohort study utilized the National Health Insurance Research Database in Taiwan to identify patients who underwent primary TJA over a 15-year period (January 2000-December 2015 inclusive). Study participants were further categorized into two groups, bisphosphonate users and nonusers, using propensity score matching. The Kaplan-Meier curve analysis and adjusted hazard ratios (aHRs) of revision surgery, adverse outcomes of primary surgery and subsequent TJA were calculated using Cox regression analysis. This study analyzed data from 6485 patients who underwent total hip arthroplasty (THA) and 20,920 patients who underwent total knee arthroplasty (TKA). The risk of revision hip and knee arthroplasty was significantly lower in the bisphosphonate users than in the nonusers (aHR, 0.54 and 0.53, respectively). Furthermore, the risk of a subsequent total joint arthroplasty, adverse events and all-cause mortality were also significantly reduced in the bisphosphonate users. This study, involving a large cohort of patients who underwent primary arthroplasties, revealed that bisphosphonate treatment may potentially reduce the risk of revision surgery and associated adverse outcomes. Furthermore, the use of bisphosphonates after TJA is also associated with a reduced need for subsequent arthroplasty.Research Registration Unique Identifying Number (UIN): ClinicalTrials.gov Identifier-NCT05623540 ( https://clinicaltrials.gov/show/NCT05623540 ).

Fucoidan from Ascophyllum nodosum and Undaria pinnatifida attenuate SARS-CoV-2 infection in vitro and in vivo by suppressing ACE2 and alleviating inflammation.

The global healthcare challenge posed by COVID-19 necessitates the continuous exploration for novel antiviral agents. Fucoidans have demonstrated antiviral activity. However, the underlying structure-activity mechanism responsible for the inhibitory activity of fucoidans from Ascophyllum nodosum (FUCA) and Undaria pinnatifida (FUCU) against SARS-CoV-2 remains unclear. FUCA was characterized as a homopolymer with a backbone structure of repeating (1 â†’ 3) and (1 â†’ 4) linked α-l-fucopyranose residues, whereas FUCU was a heteropolysaccharide composed of Fuc1-3Gal1-6 repeats. Furthermore, FUCA demonstrated significantly higher anti-SARS-CoV-2 activity than FUCU (EC50: 48.66 vs 69.52 µg/mL), suggesting the degree of branching rather than sulfate content affected the antiviral activity. Additionally, FUCA exhibited a dose-dependent inhibitory effect on ACE2, surpassing the inhibitory activity of FUCU. In vitro, both FUCA and FUCU treatments downregulated the expression of pro-inflammatory cytokines (IL-6, IFN-α, IFN-γ, and TNF-α) and anti-inflammatory cytokines (IL-10 and IFN-ß) induced by viral infection. In hamsters, FUCA demonstrated greater effectiveness in attenuating lung and gastrointestinal injury and reducing ACE2 expression, compared to FUCU. Analysis of the 16S rRNA gene sequencing revealed that only FUCU partially alleviated the gut microbiota dysbiosis caused by SARS-CoV-2. Consequently, our study provides a scientific basis for considering fucoidans as poteintial prophylactic food components against SARS-CoV-2.

An investigation for the efficacy of teaching model of combining virtual simulation and real experiment for clinical microbiology examination.

Background: As a convenient teaching tool, virtual simulation experiment technology had been widely utilized in the field of medical education. However, virtual learning could not fully replace the benefits of in-person instruction. Therefore, finding ways to integrate both methods was crucial for achieving optimal educational outcomes. The objective of this study was to compare the effectiveness of the self-built virtual simulation and design experiment combining teaching mode and the traditional experimental teaching mode in the clinical microbiology examination experiment teaching. Methods: This study was conducted at Shandong First Medical University in China. The experimental group consisted of 100 third-year students from the grade 2020 majoring in medical examination technology, who underwent an innovative teaching model combining virtual and real experiments. The control group comprised of 100 third-year students from the grade 2019 in the same major, who received traditional experimental teaching model. In this study, we referred to grade 2020 as cohort 2020 and grade 2019 cohort 2019. The performance of both groups was assessed via experimental and theoretical testing. Meanwhile, survey questionnaires were administered to evaluate the efficacy of the innovative experimental teaching model and students' level of satisfaction with it. Cohort 2020 conducted a survey for modules 1 to 4, while cohort 2019 only conducted a survey for module 4, as detailed in the Appendix. Results: The majority of students in the experimental group expressed satisfaction with the teaching model that combined virtual and real experiments, as evidenced by their superior performance on both experimental operational skills (87.54 ± 8.93 vs. 82.39 ± 10.55) and theoretical knowledge tests (83.65 ± 9.02 vs. 80.18 ± 8.24) compared to those in the control group. Conclusion: The combination of virtual simulation experiment and design experiment in the microbiological examination of clinical specimens represented an effective pedagogical approach. The instructional approach had the potential to incite a passion for learning, enhance proficiency in standardized experimental techniques, foster the ability to integrate theory with practice, and cultivate clinical reasoning skills.

Association between bilateral condylar resorption and reduced volumes of the craniofacial skeleton and masticatory muscles in adult patients: A retrospective study.

Objectives: This retrospective cohort study aimed to analyze volumes of craniomaxillofacial bone and masticatory muscles of young adults with bilateral idiopathic condylar resorption. Methods: This was a retrospective cohort study of 84 adults with bilateral idiopathic condylar resorption (BCR) and 48 adults with normal temporal-mandibular joint (TMJ) matched for age and sex (mean age, 23.2 ± 3.6 years). The volumes of craniomaxillofacial bone and masticatory muscles, as well as intercondylar angle were measured. Unpaired t-tests and Pearson correlation tests were applied to analyze the data. Multivariable linear regression models were used to estimate the association between bilateral condylar volume and volumes of craniomaxillofacial bone and masticatory muscles adjusted for age, sex, and disc status. Results: Compared to the control group, the BCR group displayed significant decreased volumes of craniomaxillofacial bone (p < 0.001), craniomaxillofacial bone without mandible (p < 0.001), mandible (p < 0.001), mandible without mandibular condylar process (p < 0.001), bilateral masseter muscle (p < 0.001) and bilateral temporalis muscle (p < 0.001), as well as the intercondylar angle (p < 0.001). These variables were significantly correlated to the volume of mandibular condylar process (0.5< r < 0.8; p < 0.001). By linear regression analyses, significant associations were found for the bilateral condylar volume with craniomaxillofacial bone volume and mandible bone volume. Conclusions: Young adults with BCR displayed smaller volumes of craniomaxillofacial skeleton and masticatory muscles, and smaller intercondylar angle than the normal patients. The craniofacial musculoskeletal volume and intercondylar angle are associated with mandibular condylar process volume.

Imaging evaluation of disc position and status after temporomandibular joint arthroscopic disc repositioning and suturing surgery.

Objective: This study aimed to explain the change of disc position at different over-corrected place after arthroscopic disc repositioning and suturing surgery. Study design: Patients treated with temporomandibular joint arthroscopic disc repositioning and suturing surgery were reviewed. All patients underwent magnetic resonance imaging (MRI) before, immediately after surgery and at 2-year follow-up. The position of disc was checked and the change was compared. Results: 133 patients were included in the final analysis with 203 TMJ sides. The incidence rate for anterior movement of the disc after surgery was 33.0 %. Disc repositioned between 12 and 1 o'clock showed smaller movement rate of 22.6 %, while higher movement rate of 53.6 % was seen when repositioned between 2 and 3 o'clock. Conclusions: After arthroscopic disc repositioning and suturing surgery for ADD patients, the repositioned disc showed tendency to move forward. 12 to 1 o'clock was optional disc site for repositioning while excessive over-correction was not recommended.

Feasibility of simultaneous TMJ arthroscopy in ADDwoR patients undergoing orthognathic surgery for jaw deformity.

This study evaluated the feasibility of simultaneous temporomandibular joint (TMJ) arthroscopy and orthognathic surgery as a new treatment strategy for anterior disc displacement without reduction (ADDwoR) patients with severe jaw deformities. Twelve ADDwoR patients with facial deformities who underwent arthroscopy and orthognathic surgery between September 2015 and December 2019 were retrospectively evaluated. Pre- and postoperative maximum incisal opening (MIO) and joint pain were recorded. Computed tomography (CT) and three-dimensional cephalometric analysis were performed at 3 (T1) and ≥6 (T2) months postoperatively. Magnetic resonance imaging (MRI) of the TMJ was performed before, ≤7 days after and ≥6 months after surgery. The lateral profile radiological findings, the symmetry of the maxilla and mandible, and the MRI measurements were compared. Anterior disc displacement did not recur, and the maximum incisal opening (MIO) increased from 27.4 mm to 32.7 mm after surgery (p < 0.05). No significant differences were found in the lateral profile, symmetry indices or condylar height via MRI between T1 and T2. Joint morphology and the position of both the maxilla and mandible remained stable during postoperative follow-up, while joint symptoms were markedly relieved and facial appearance was noticeably improved. Combined arthroscopy and orthognathic surgery is effective and recommended for ADDwoR patients with jaw deformities.

Phenotypic and metabolomic characteristics of mouse models of metabolic associated steatohepatitis.

BACKGROUND: Metabolic associated steatohepatitis (MASH) is metabolic disease that may progress to cirrhosis and hepatocellular carcinoma. Mouse models of diet-induced MASH, which is characterized by the high levels of fats, sugars, and cholesterol in diets, are commonly used in research. However, mouse models accurately reflecting the progression of MASH in humans remain to be established. Studies have explored the potential use of serological metabolites as biomarkers of MASH severity in relation to human MASH. METHODS: We performed a comparative analysis of three mouse models of diet-induced MASH in terms of phenotypic and metabolomic characteristics; MASH was induced using different diets: a high-fat diet; a Western diet; and a high-fat, high-cholesterol diet. Liver cirrhosis was diagnosed using standard clinical approaches (e.g., METAVIR score, hyaluronan level, and collagen deposition level). Mouse serum samples were subjected to nuclear magnetic resonance spectroscopy-based metabolomic profiling followed by bioinformatic analyses. Metabolomic analysis of a retrospective cohort of patients with hepatocellular carcinoma was performed; the corresponding cirrhosis scores were also evaluated. RESULTS: Using clinically relevant quantitative diagnostic methods, the severity of MASH was evaluated. Regarding metabolomics, the number of lipoprotein metabolites increased with both diet and MASH progression. Notably, the levels of very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) significantly increased with fibrosis progression. During the development of diet-induced MASH in mice, the strongest upregulation of expression was noted for VLDL receptor. Metabolomic analysis of a retrospective cohort of patients with cirrhosis indicated lipoproteins (e.g., VLDL and LDL) as predominant biomarkers of cirrhosis. CONCLUSIONS: Our findings provide insight into the pathophysiology and metabolomics of experimental MASH and its relevance to human MASH. The observed upregulation of lipoprotein expression reveals a feedforward mechanism for MASH development that may be targeted for the development of noninvasive diagnosis.

Attenuative effects of collagen peptide from milkfish (Chanos chanos) scales on ovariectomy-induced osteoporosis.

Osteoporosis is characterized by low bone mass, bone microarchitecture disruption, and collagen loss, leading to increased fracture risk. In the current study, collagen peptides were extracted from milkfish scales (MS) to develop potential therapeutic candidates for osteoporosis. MS was used to synthesize a crude extract of fish scales (FS), collagen liquid (COL), and hydroxyapatite powder (HA). COL samples were further categorized according to the peptide size of total COL (0.1 mg/mL), COL < 1 kDa (0.1 mg/mL), COL: 1-10 kDa (0.1 mg/mL), and COL > 10 kDa (0.1 mg/mL) to determine it. Semi-quantitative reverse transcription polymerase chain reaction (sqRT-PCR) and immunofluorescence labeling were used to assess the expression levels of specific mRNA and proteins in vitro. For in vivo studies, mice ovariectomy (OVX)-induced postmenopausal osteoporosis were developed, while the sham surgery (Sham) group was treated as a control. Collagen peptides (CP) from MS inhibited osteoclast differentiation in RAW264.7 cells following an insult with nuclear factor kappa-B ligand (RANKL). CP also enhanced osteoblast proliferation in MG-63 cells, possibly through downregulating NFATc1 and TRAP mRNA expression and upregulating ALP and OPG mRNA levels. Furthermore, COL1 kDa also inhibited bone density loss in osteoporotic mice. Taken together, CP may reduce RANKL-induced osteoclast activity while promoting osteoblast synthesis, and therefore may act as a potential therapeutic agent for the prevention and control of osteoporosis.

Factors Influencing Mandibular Deviation: A Retrospective Clinical Study.

This study aimed to investigate the correlation between mandibular deviation (MD) and possible clinical factors in patients with anterior disc displacement (ADD). This retrospective clinical study enrolled 296 patients with ADD, diagnosed using magnetic resonance imaging, from 2015 to 2018. The clinical symptoms and medical histories of these patients were carefully examined and recorded. Mandibular deviation was the primary outcome variable confirmed by a combination of clinical examination and facial photographs or posteroanterior cephalograms. The primary predictor variable was ADD staging. Secondary predictor variables included condylar height and distance of disc displacement. Other predictor variables were age, sex, disease course, oral parafunctions, depression, and bone mineral density. We used logistic regression to examine the correlation between the MD and all predictor variables. The χ2 test and analysis of variance were used to exclude the correlation between the predictor variables. In this study, the prevalence of MD was 77% among 278 patients with ADD. Bilateral ADD staging significantly contributed to MD on both sides. The odds ratio increased with the deterioration of disc displacement. The present study demonstrated that the ADD staging influences the condylar height and MD, and that articular disk position should be considered while treating MD.

Design strategies and recent development of bioactive modulators for glutamine transporters.

Glutamine transporters are integral to the metabolism of glutamine in both healthy tissues and cancerous cells, playing a pivotal role in maintaining amino acid balance, synthesizing biomolecules, and regulating redox equilibrium. Their critical functions in cellular metabolism make them promising targets for oncological therapies. Recent years have witnessed substantial progress in the field of glutamine transporters, marked by breakthroughs in understanding of their protein structures and the discovery of novel inhibitors, prodrugs, and radiotracers. This review provides a comprehensive update on the latest advancements in modulators targeting the glutamine transporter, with special attention given to LAT1 and ASCT2. It also discusses innovative approaches in drug design aimed at these transporters.

DriverDBv4: a multi-omics integration database for cancer driver gene research.

Advancements in high-throughput technology offer researchers an extensive range of multi-omics data that provide deep insights into the complex landscape of cancer biology. However, traditional statistical models and databases are inadequate to interpret these high-dimensional data within a multi-omics framework. To address this limitation, we introduce DriverDBv4, an updated iteration of the DriverDB cancer driver gene database (http://driverdb.bioinfomics.org/). This updated version offers several significant enhancements: (i) an increase in the number of cohorts from 33 to 70, encompassing approximately 24 000 samples; (ii) inclusion of proteomics data, augmenting the existing types of omics data and thus expanding the analytical scope; (iii) implementation of multiple multi-omics algorithms for identification of cancer drivers; (iv) new visualization features designed to succinctly summarize high-context data and redesigned existing sections to accommodate the increased volume of datasets and (v) two new functions in Customized Analysis, specifically designed for multi-omics driver identification and subgroup expression analysis. DriverDBv4 facilitates comprehensive interpretation of multi-omics data across diverse cancer types, thereby enriching the understanding of cancer heterogeneity and aiding in the development of personalized clinical approaches. The database is designed to foster a more nuanced understanding of the multi-faceted nature of cancer.

Effect of arthroscopic discopexy on condylar growth in adolescents with temporomandibular joint disc displacement without reduction: A retrospective self-controlled case series study.

This study was a retrospective self-controlled study that aimed to evaluate the effect of arthroscopic discopexy on condylar height and mandibular position in adolescents with temporomandibular joint (TMJ) anterior disc displacement without reduction (ADDwoR). Patients between 10 and 20 years of age and diagnosed with bilateral TMJ ADDwoR by magnetic resonance image (MRI) were included in this study. All patients underwent a period of natural course before arthroscopic surgery and then a follow-up period postoperatively. Changes in condylar height and mandibular position were measured by MRI and X-ray radiographs. Data were analyzed by paired t-test, Pearson correlation analysis, and generalized estimating equations. This study comprised a total of 40 patients with a mean age of 14.80 years. Pearson correlation analysis showed correlations between condylar height and mandibular position changes. The condylar height change during the post-operative period was significantly higher than that during natural course period (3.57 mm, p < 0.001). The changes in mandibular position (including ANB angle, SNB angle, and Pog-Np) were significant different (all p < 0.05) between the two periods. This study found that arthroscopic discopexy can promote condylar growth and correct dentofacial deformity in adolescents with bilateral TMJ ADDwoR.

Identification of FXYD6 as the novel biomarker for glioma based on differential expression and DNA methylation.

OBJECTIVE: As a single-transmembrane protein of the FXYD family, FXYD6 plays different roles under physiological and pathological status, especially in the nervous system. This study aims to identify FXYD6 as a biomarker for glioma, by analyzing its expression and methylation patterns. METHODS: Using TCGA and GTEx datasets, we analyzed FXYD6 expression in various tissues, confirming its levels in normal brain and different glioma grades via immunoblotting and immunostaining. FXYD6 biological functions were explored through enrichment analysis, and tumor immune infiltration was assessed using ESTIMATE and TIMER algorithms. Pearson correlation analysis probed FXYD6 associations with biological function-related genes. A glioma detection model was developed using FXYD6 methylation data from TCGA and GEO. Consistently, a FXYD6 methylation-based prognostic model was constructed for glioma via LASSO Cox regression. RESULTS: FXYD6 was observed to be downregulated in GBM and implicated in a range of cellular functions, including synapse formation, cell junctions, immune checkpoint, ferroptosis, EMT, and pyroptosis. Hypermethylation of specific FXYD6 CpG sites in gliomas was identified, which could be used to build a diagnostic model. Additionally, FXYD6 methylation-based prognostic model could serve as an independent factor as well. CONCLUSIONS: FXYD6 is a promising biomarker for the diagnosis and prognosis of glioma, with its methylation-based prognostic model serving as an independent factor. This highlights its potential in clinical application for glioma management.