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Abstract Telomerase reverse transcriptase promoter (TERTp) mutations are associated with non-radioiodine avidity. However, the role of these mutations in the clinical outcomes of patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) remains unknown. Herein, we aim to analyze gene mutations and clinical manifestations to verify TERTp’s role in driving disease progression to RAIR-DTC and clinical outcomes. Next-generation sequencing data and clinical data were obtained from 243 patients with DTC. Of the 25 patients with TERTp mutations, 80% (20/25) had RAIR-DTC. RAIR-DTC was significantly less prevalent in patients with BRAF V600E (9/143, 6.3%) than those with both BRAF V600E and TERTp mutations (14/17, 82.4%). Patients with RAIR-DTC harboring both BRAF V600E and TERTp mutations were more likely to have > 3 distant metastatic sites (85.7%, 12/14) than those with BRAF V600E alone (33.3%, 3/9). Only one patient with both BRAF V600E and TERTp mutations had non-RAIR-DTC. The time from initial radioactive iodine therapy to RAIR-DTC diagnosis was significantly shorter in patients with TERTp mutations than in those without. Patients with BRAF V600E and TERTp mutations progressed faster to RAIR-DTC than those with BRAF V600E alone (p

Myeloid-derived suppressor cells (MDSCs) are closely related to the occurrence and development of many cancers, but the specific mechanism is not fully understood. It has been found that N6-methyladenosine (m6A) plays a key role in RNA metabolism, but its function in MDSCs has yet to be revealed. In this study, we found that MDSCs in mice with colorectal cancer (CRC) have significantly elevated levels of m6A, while ALKBH5 expression is decreased. Overexpression of ALKBH5 can reduce the immunosuppressive function of MDSCs in vivo and in vitro, and attenuates the protumorigenic ability of MDSCs. Mechanism study found that the overexpression of ALKBH5 in MDSCs reduced the m6A modification level of Arg-1 mRNA, and then weakened the stability of Arg-1 mRNA and protein expression. These data suggest that the decreased expression of ALKBH5 in CRC tumor mice may promote the expression of Arg-1, enhance the immunosuppressor function of MDSCs, and promote tumor growth. These findings highlight that ALKBH5 may regulate the function of MDSCs in tumor-bearing mice and may be a new target for immunotherapy. This research provides a new perspective for our understanding of the role of MDSCs in cancer development, and also brings new hope for cancer treatment.

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition that affects the digestive system and includes Crohn’s disease (CD) and ulcerative colitis (UC). Although the exact etiology of IBD remains uncertain, dysfunctional immunoregulation of the gut is believed to be the main culprit. Amongst the immunoregulatory factors, reactive oxygen species (ROS) and reactive nitrogen species (RNS), components of the oxidative stress event, are produced at abnormally high levels in IBD. Their destructive effects may contribute to the disease’s initiation and propagation, as they damage the gut lining and activate inflammatory signaling pathways, further exacerbating the inflammation. Oxidative stress markers, such as malondialdehyde (MDA), 8-hydroxy-2’-deoxyguanosine (8-OHdG), and serum-free thiols (R-SH), can be measured in the blood and stool of patients with IBD. These markers are elevated in patients with IBD, and their levels correlate with the severity of the disease. Thus, oxidative stress markers can be used not only in IBD diagnosis but also in monitoring the response to treatment. It can also be targeted in IBD treatment through the use of antioxidants, including vitamin C, vitamin E, glutathione, and N-acetylcysteine. In this review, we summarize the role of oxidative stress in the pathophysiology of IBD, its diagnostic targets, and the potential application of antioxidant therapies to manage and treat IBD.

Understanding the invasion of moso bamboo (Phyllostachys edulis) into adjacent evergreen broadleaf forest based on functional traits is crucial due to its significant influence on ecosystem processes. However, existing research has primarily focused on above- or below-ground traits in isolation, lacking a comprehensive integration of both. In this study, we conducted a trait-based analysis including 23 leaf traits and 11 root traits in three forest types - bamboo forest, mixed bamboo and broadleaf forest, and evergreen broadleaf forest - to investigate trait differences, phenotypic integration, and above- and below-ground resource strategies in bamboo and broadleaf species. Our findings demonstrated significant differences in leaf and root key traits between bamboo and broadleaf species, strongly supporting the “phenotypic divergence hypothesis”. Bamboo exhibited stronger trait correlations compared to broadleaf species, indicating higher phenotypic integration. Above- and below-ground strategies were characterized by trade-offs rather than coordination, resulting in a multi-dimensional trait syndrome. Specifically, a unidimensional leaf economics spectrum revealed that bamboo with higher leaf N concentrations (LNC), P concentrations (LPC), and specific leaf area (SLA) adopted a “fast acquisitive” above-ground strategy, while broadleaf species with thicker leaves employed a “slow conservative” above-ground strategy. A two-dimensional root trait syndrome indicated a “conservation” gradient with bamboo adopting a “slow conservative” below-ground strategy associated with higher root tissue density (RTD), and broadleaf species exhibiting a “fast acquisitive” below-ground strategy linked to higher root N concentrations (RNC) and P concentrations (RPC), and a “collaboration” gradient probably ranging from broadleaf species with a “do-it-yourself” strategy characterized by high specific root length (SRL), to bamboo adopting an “outsourcing” strategy with thicker roots. In conclusion, key trait divergence from coexisting broadleaf species, higher phenotypic integration, and multi-dimensional opposite above- and below-ground resource strategies confer competitive advantages to moso bamboo, shedding light on the mechanistic understanding of its invasion into subtropical evergreen broadleaf forest and providing theoretical guidance for maintaining the stability of subtropical forest ecosystem.

Introduction The potential positive impact of computer game playing on cognitive function and its potential role in reducing the risk of Alzheimer's disease (AD) has been suggested. However, current observational studies have certain limitations. We utilized Mendelian randomization (MR) alongside extensive genome-wide association study (GWAS) data to examine the relationship between computer game playing, cognitive function, risk of AD, and levels of brain-derived neurotrophic factor (BDNF). Methods We collected datasets on computer game playing, cognition function, risk of AD, and BDNF level from the IEU Open GWAS project. Causal effects were assessed using various MR methods, including inverse variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. To ensure the accuracy of the results, sensitivity analyses were conducted. Results Our analysis revealed a significant association between computer game playing and cognitive function ( β = 0.801, 95% CI: 0.351, 1.328, P = 0.001). There was no statistically significant association between computer game playing and either BDNF level or risk of AD ( β = −0.112, 95%CI: −1.315, 1.091, P = 0.855; OR = 1.000, 95% CI: 1.004, 0.997, P = 0.891, respectively). We further confirmed the reliability of our evidence through the MR-Egger intercept test, MR-PRESSO global test, Cochran's Q test, and funnel plots. Conclusion The results of our study indicate that engaging in computer game playing may confer a safeguarding influence on cognitive function. This underscores the potential advantages associated with computer gaming. Nevertheless, given the constraints inherent in our research, further investigation is warranted to substantiate our findings and delve into the underlying mechanisms.

Chronic inflammation of the alveolar bones and connective tissues supporting teeth causes periodontal disease, one of the most prevalent infectious diseases in humans. It was previously reported that oral cancer was the sixth most common cancer in the world, followed by squamous cell carcinoma. Periodontal disease has been linked to an increased risk for oral cancer in some studies, and these studies have found a positive relationship between oral cancer and periodontal disease. In this work, we aimed to explore the potential correlation between oral squamous cell carcinoma (OSCC) and Periodontal disease. The single-cell RNA sequence analysis was applied to explore the genes that were closely associated with cancer-associated fibroblasts (CAFs). the head and neck squamous cell carcinoma. The Single sample Gene Set Enrichment Analysis (ssGSEA) algorithm was applied to explore the scores of CAFs. Subsequently, the differentially expressed analysis was applied to explore the CAFs-related genes that play a key role in the OSCC cohort. The LASSO regression analysis and the COX regression analysis were applied to construct the CAFs-based periodontal disease-related risk model. In addition, the correlation analysis was used to explore the correlation between the risk model and clinical features, immune-related cells, and immune-related genes. By using the single-cell RNA sequence analysis, we successfully obtained the biomarkers for the CAFs. Finally, we successfully obtained a six-CAFs-related genes risk model. The ROC curve and survival analysis revealed that the risk model showed good predictive value in OSCC patients. Our analysis successfully provided a new direction for the treatment and prognosis of OSCC patients.