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m6A, m5C and m7G are common types of RNA methylation modifications that are widely involved in key mechanisms regulating malignancy. However, the role of RNA methylation-related genes in the immune microenvironment of bladder cancer (BLCA) remains elusive. In this study, we established RNA methylation molecular subtypes by analyzing the TCGA and GEO datasets. Risk model and nomogram were constructed by LASSO and multivariate Cox regression analysis and validated by external datasets. Genetic variations, functional enrichment analysis and immune cell infiltration were analyzed. The expression levels of hub genes were detected by real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The effect of FN1 on cellular function was determined using experimental assays. Finally, we identified a 7-gene signature associated with BLCA prognosis. GSE19423 validated the predictive value of the risk model. The IMvigor210 data showed the model had promising predictive efficacy for BLCA immunotherapy. Significant differences in biological function, immune cell infiltration and drug sensitivity were observed between high- and low-risk groups. Furthermore, FN1 was upregulated in BLCA, as determined by qRT-PCR and IHC. Depletion of FN1 using siRNA impaired cell motility in T24 and 5637 cells. In conclusion, RNA methylation-related risk model can predict the prognosis, immune landscape and response to immunotherapy in BLCA. Among the 7-gene signature, FN1 is a pivotal gene that promotes the migration of bladder cancer cells.

The purpose of this study was to evaluate variations in the regional incidence of glioblastoma in US adults in 2004-2013. We evaluated 24,262 patients with primary glioblastoma. Data were categorized based on geographic regions that included different SEER registry sites as follows: (1) Northeast: Connecticut, New Jersey (3,977 patients); (2) South: Kentucky, Louisiana, Metropolitan Atlanta, Rural Georgia, Greater Georgia (excluding AT and RG) (5,212 patients); (3) North Central: Metropolitan Detroit, Iowa (2,320 patients); (4) West: Hawaii, New Mexico, Seattle (Puget Sound), Utah, San Francisco-Oakland SMSA, San Jose-Monterey, Los Angeles, Greater California (excluding SF, LA, and SJ), Alaska (12,753 patients). Statistically significant differences in the rates of overall patient survival ( < 0.001) and the incidence of glioblastoma (24.31, 22.6, 20.35, 15.03 per 100,000/year in the South, Northeast, West, North Central regions, respectively) were identified between geographic regions. Multivariate Cox regression analysis demonstrated that overall survival was better in patients of Asian or Pacific Islander race. In addition, age, registry site, marital status, tumor laterality, histological classification, the extent of disease, tumor size, tumor extension, and treatment methods were identified as significant prognostic factors. Glioblastoma incidence is geographic region and race/ethnicity-dependent.

With the development of new power systems with high proportions of renewable energy and high proportions of power electronics equipment, the influence of broadband electromagnetic oscillations in power systems is becoming more and more significant. In order to better grasp the dynamic characteristics of broadband oscillations, a new adaptive band-pass filter and VMD-Esprit based multi-modal monitoring method is proposed for broadband electromagnetic oscillation in “double high” power systems. First, based on the mode frequency and amplitude information provided by FFT mode detection, the proposed adaptive band-pass filter adaptively sets the center frequency, bandwidth, and other parameters and extracts or separates the voltage/current signal in each frequency band. Second, the filtered signals are corrected and compensated, and then the VMD modal decomposition of each frequency band signal is combined with Esprit for parameter identification so as to obtain the waveform and parameter information of each mode. Finally, the separation, correction, and parameter identification of multi-mode broadband oscillation waveforms are carried out. The experimental results show that frequency division processing can reduce the computation and improve real-time performance. In the processing of signals in the frequency band, the center frequency, bandwidth, and other parameters can be adjusted adaptively under different conditions of single-mode composition or multi-mode composition, which improves the accuracy of VMD decomposition and increases the flexibility of signal processing. Meanwhile, it overcomes the defects such as the inaccuracy of traditional mode recognition, which provides a new idea for broadband electromagnetic oscillation analysis.

Background A significant challenge in bladder cancer treatment is primary chemoresistance, in which cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) play a pivotal role. While the contributions of CAFs to tumor progression and drug resistance are well established, the precise molecular mechanisms by which they induce chemoresistance remain unclear. A comprehensive understanding of the effect of TME modulation—particularly through CAFs—on the chemotherapeutic response is crucial for developing effective strategies to overcome chemoresistance and improve patient survival. Methods Primary fibroblasts were isolated from paired clinical samples of bladder cancer tissues and adjacent normal tissues to identify key CAF-derived secretory factors. Bioinformatics analysis, semiquantitative RT‒qPCR, and dual-luciferase reporter assays were subsequently used to investigate the functional role and mechanistic basis of CXCL14 in chemoresistance. The therapeutic relevance of these findings was further evaluated through in vitro and in vivo models, including ex vivo patient-derived organoid (PDO) models, by assessing cisplatin sensitivity and validating therapeutic targeting of the CXCL14-CCR7-STAT3 axis with small molecule inhibitors. Results Compared to normal fibroblasts and CAFs from nonchemoresistance groups, CAFs derived from cisplatin-resistant patients demonstrated significantly greater paracrine-mediated induction of chemoresistance. Mechanistically, CAF-secreted CXCL14 engaged CCR7 on bladder cancer cells, triggering STAT3 phosphorylation and consequently upregulating the DNA repair gene ERCC4 to promote cisplatin resistance. In vivo validation confirmed that pharmacological CCR7 or STAT3 inhibition markedly reversed chemoresistance and potentiated cisplatin-induced tumor cell death. Notably, STAT3 activation mediated the overexpression of the glycolytic enzymes HK2 and LDHA, resulting in greater glycolytic flux in resistant cells. This metabolic reprogramming further facilitated the transdifferentiation of normal fibroblasts into CXCL14-secreting CAFs, establishing a self-reinforcing feedback loop that sustains chemoresistance. Conclusion The CXCL14/CCR7/STAT3 axis critically mediates cisplatin resistance in bladder cancer through dual modulation of DNA repair and glycolytic metabolism. Therapeutic cotargeting of this pathway with CCR7 or STAT3 inhibitors combined with cisplatin represents a promising strategy to overcome chemoresistance and improve clinical outcomes.

Nucleolar protein 3 (NOL3), as a markedly increased protein across a range of tumors, has been well acknowledged that plays an anti-apoptotic role in malignancies, while some novel impacts of NOL3 on metastasis and chemoresistance are demonstrated recently. In this study, we uncover another role of NOL3 on promoting proliferation in bladder cancer (BLCA). The reduction of NOL3 significantly inhibited cell proliferation, and we detected the stable cell cycle arrest after knockdown of NOL3 in two-type BLCA cell lines. Mechanistically, we present the first evidence that the PI3K/Akt pathway was considerably inhibited with the decrease of NOL3 in BLCA cell lines. In addition, LY294002, a PI3K inhibitor, rescued NOL3 overexpression-mediated activation of the PI3K/Akt axis and the depression of proliferation in BLCA cell lines. In conclusion, our study suggests that NOL3 is upregulated in BLCA cells and promotes proliferation via the PI3K/Akt pathway, indicating that NOL3 may be a potential therapeutic target for BLCA.

Background Infertility is a major reproductive health issue affecting childbearing-age couples worldwide. Factors contributing to its increasing prevalence include delayed marriage and childbearing decisions, as well as exposure to environmental pollutants. In addition to directly causing fertility problems, infertility also negatively affects family relationships by causing psychological trauma, such as anxiety and depression, thereby reducing quality of life. Emotional state, fertility-related stress, fertility quality of life (FertiQoL), and coping strategies are associated with psychological resilience. However, according to existing studies, the relationships among coping strategies, FertiQoL, and psychological resilience, as well as the synergistic pathways between the former two and psychological resilience, remain unclear. The purpose of this study is to investigate the associations among coping strategies, FertiQoL, and psychological resilience. Additionally, it aims to investigate whether different coping strategies serve as a mediator between FertiQoL and psychological resilience. Method This study employed a cross-sectional research design and purposive sampling method. A total of 222 patients with infertility who visited a tertiary-level hospital in Hunan Province between January and December 2019 were selected as the study subjects. We measured psychological resilience specifically in those who reported an unfulfilled wish for a child. Additionally, FertiQoL and coping strategies were assessed. We used Pearson’s product moment correlation to examine the association of psychological resilience, FertiQoL and coping strategies. Using the Process v4.1 model, we examined the mediating function of various coping strategies in the association between psychological resilience and FertiQoL, and employed stratified multiple regression analysis to investigate the factors influencing psychological resilience. Results In total, 222 patients with infertility presented psychological resilience scores that were below the Chinese norm (M = 66.34; SD = 13.90) and were moderately low (M = 60.42; SD = 12.18). Pearson’s correlation analyses revealed significant bivariate associations among the study variables. FertiQoL demonstrated a weak but statistically significant negative correlation with psychological resilience ( r =-.149, p  < .05), whereas both positive coping ( r  = .261, p  < .05) and meaning-based coping strategies ( r  = .377, p  < .05) showed moderate positive correlations. In contrast, neither active avoidance ( r =-.029, p  > .05) nor passive avoidance strategies ( r  = .115, p  > .05) were significantly associated with psychological resilience. In the mediation analysis adjusted for covariates, introducing positive and meaning-based coping strategies as mediators significantly attenuated the standardized coefficient of the FertiQoL-resilience association, which decreased from B =-0.172 to B =-0.329. These results demonstrate that both coping strategies play a significant mediating role in the relationship between FertiQoL and psychological resilience, with positive coping strategies having an indirect effect on psychological resilience of 0.074 (95% CI [0.010, 0.140]) and meaning-based coping strategies having an indirect effect of 0.083 (95% CI [0.030, 0.149]). The magnitude of the mediated effect was 34.81% overall. Conclusion Infertility patients’ psychological resilience and FertiQoL are related, and positive coping and meaning-based coping strategies have some mediating effects on this relationship, indicating that these strategies may be important in reducing the detrimental effects of FertiQoL on psychological resilience. Positive coping and meaning-based coping strategies have been shown to be effective at preserving patients’ psychological well-being. These findings serve as a foundation for future research into focused intervention programs.

Exercise has been shown to alleviate depressive symptoms and enhance bodily functions. However, the precise mechanisms underlying its antidepressant effects remain incompletely understood. In this study, we observed that treadmill exercise may exert antidepressant effects in a chronic restraint stress (CRS) mouse model by modulating the proinflammatory Growth Differentiation Factor 15 (GDF15)‐extracellular signal‐regulated kinase (ERK) signaling pathway. Treadmill exercise improved cognitive behaviors in CRS mice and alleviated neuroinflammation, as evidenced by decreased expression of TNF‐α, IL‐1β, IL‐6, and attenuated microglia activation. Intriguingly, we found that treadmill exercise inhibited the expression of GDF15, a biomarker associated with many immune disorders, which is increased following CRS. Mechanistically, treadmill exercise may attenuate neuroinflammation by suppressing GDF15‐induced ERK activation. We thus identified a novel mechanism by which treadmill exercise attenuates depression. Modulation of the GDF15‐ERK pathway may have therapeutic implications for depression.

BACKGROUND: The cephalic vein is often used in for arteriovenous fistula creation; however, the cephalic vein variation is common. This study will propose new theoretical explanations for a new discovered variation of cephalic vein draining into external jugular vein with “T-junction” shape by means of 3D computational haemodynamic modelling, which may provide reference for clinical practice. MATERIALS AND METHODS: The precise measurements were conducted for the variant right cephalic vein draining into external jugular vein and for a normal right cephalic vein as a control. After processing the anatomical data, 3D geometrical model was reconstructed. Then, the influent field inside the variant jugulocephalic vein was mathematically modelled to get a detailed description of haemodynamic environment. RESULTS: The anatomical parameters of the “T-junction” jugulocephalic vein variant were much more different from the normal right cephalic vein. The wall shear stress of variant cephalic vein at the corresponding position was higher and changed more rapidly than that of normal cephalic vein. The shear rate contour lines are disordered in several areas of the variant cephalic vein, indicating that the haemodynamic parameters in these areas are unstable. The haemodynamic characteristics at the confluence of the variant cephalic vein are more complex, with more areas where haemodynamic parameters are disrupted. CONCLUSIONS: The variation of cephalic arch in a “T-junction” with external jugular vein largely altered the fluid dynamics, especially in haemodialysis patients with brachiocephalic fistula in terms of the simulating flow in 3D computational model. This computational model provides haemodynamic profiles for stabilizing or modulating fluid dynamics in patients with jugulocephalic vein variant after brachiocephalic fistula.

Autophagy-dependent cisplatin resistance poses a challenge in bladder cancer treatment. SIRT1, a protein deacetylase, is involved in autophagy regulation. However, the precise mechanism through which SIRT1 mediates cisplatin resistance in bladder cancer via autophagy remains unclear. In this study, we developed a cisplatin-resistant T24/DDP cell line to investigate this mechanism. The apoptosis rate and cell viability were assessed using flow cytometry and the CCK8 method. The expression levels of the relevant RNA and protein were determined using RT-qPCR and a Western blot analysis, respectively. Immunoprecipitation was utilized to validate the interaction between SIRT1 and Beclin1, as well as to determine the acetylation level of Beclin1. The findings indicated the successful construction of the T24/DDP cell line, which exhibited autophagy-dependent cisplatin resistance. Inhibiting autophagy significantly reduced the drug resistance index of these cells. The T24/DDP cell line showed a high SIRT1 expression level. The overexpression of SIRT1 activated autophagy, thereby further promoting cisplatin resistance in the T24/DDP cell line. Conversely, inhibiting autophagy counteracted the cisplatin-resistance-promoting effects of SIRT1. Silencing SIRT1 led to increased acetylation of Beclin1, the inhibition of autophagy, and a reduction in the cisplatin resistance of the T24/DDP cell line. Introducing a double mutation (lysine 430 and 437 to arginine, 2KR) in Beclin-1 inhibited acetylation and activated autophagy, effectively reversing the decreased cisplatin resistance resulting from SIRT1 silencing. In summary, our study elucidated that SIRT1 promotes cisplatin resistance in human bladder cancer T24 cells through Beclin1-deacetylation-mediated autophagy activation. These findings suggest a potential new strategy for reversing cisplatin resistance in bladder cancer.

Objective This study aimed to explore whether initial hyperbaric oxygen treatment affects the stemness of glioma stem cells using an in vivo basal ganglia glioma model. Methods A basal ganglia glioma rat model was established. Rats were exposed to normal oxygen or hyperbaric oxygen on days 2, 4, 6, 8, 10, and 12. After 16 days of glioma cell inoculation, western blot, ELISA, and flow cytometry were performed to examine stemness-associated properties by examining the expression of CD133, A2B5, Nanog, oncostatin M, β-catenin, Oct-3/4, Sox2, and Nestin. Results Initial hyperbaric oxygen treatment began to affect glioma stemness-associated properties. The proportion of CD133+A2B5+ cells was significantly reduced after initial hyperbaric oxygen treatment. Additionally, the expression of stemness-related genes such as Nanog and oncostatin M was reduced, while TGF-β and β-catenin were increased. Conclusions Initial hyperbaric oxygen treatment not only alters the hypoxic microenvironment but also affects the stemness-associated properties of cancer stem cells.