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Background Malignant peritoneal mesothelioma (MPM) is a rare but aggressive cancer. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) was the preferred choice for selected patients. The purpose of this study was to thoroughly examine the impact of the combined treatment and the prognostic variables, particularly the neutrophil-to-lymphocyte ratio (NLR). Methods Characteristics of MPM patients who underwent CRS combined HIPEC treatment, followed by adjuvant chemotherapy were retrospectively collected. The univariable analysis was performed to identify the decisive influential factor. Using Kaplan-Meier analysis, the cumulative probability of survival was determined. Using Univariate Cox analysis, the prognostic factors—particularly NLR—and its correlation with survival were assessed. In the multivariate Cox proportional hazards model, predictive factors that demonstrated significance in univariate analysis were used. The degree of connection between predictors and survival was evaluated through the use of hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results A total of 64 patients were enrolled in this study. The 1, 3, 5 years survival rates were 70.3%, 65.6%, 59.4%, respectively. According to multivariate Cox analysis, patients’ survival was found to be substantially associated with post-operative NLR (HR 0.180, 0.067–0.531), Ki-67 (HR 0.184, 0.024–0.817), post-operative neutrophil count (HR 0.228, 0.075–0.696), and bidirectional pathological type (HR, 0.375, 0.146–0.964). Conclusions NLR is associated with the patients’ prognosis after CRS combined HIPEC treatment.

Pyroptosis, a form of programmed cell death (PCD), has garnered increasing attention as it relates to innate immunity and diseases. However, the involvement of pyroptosis in the mechanism by which lobaplatin acts against colorectal cancer (CRC) is unclear. Our study revealed that treatment with lobaplatin reduced the viability of HT-29 and HCT116 cells in a dose-dependent manner. Morphologically, HT-29 and HCT116 cells treated with lobaplatin exhibited microscopic features of cell swelling and large bubbles emerging from the plasma membrane, and transmission electron microscopy (TEM) revealed multiple pores in the membrane. GSDME, rather than GSDMD, was cleaved in lobaplatin-induced pyroptosis in HT-29 and HCT116 cells due to caspase-3 activation. Knocking out GSDME switched lobaplatin-induced cell death from pyroptosis to apoptosis but did not affect lobaplatin-mediated inhibition of growth and tumour formation of HT-29 and HCT116 cells in vivo and in vitro. Further investigation indicates that lobaplatin induced reactive oxygen species (ROS) elevation and JNK phosphorylation. NAC, a ROS scavenger, completely reversed the pyroptosis of lobaplatin-treated HT-29 and HCT116 and JNK phosphorylation. Activated JNK recruited Bax to mitochondria, and thereby stimulated cytochrome c release to cytosol, followed by caspase-3/-9 cleavage and pyroptosis induction. Therefore, in colon cancer cells, GSDME mediates lobaplatin-induced pyroptosis downstream of the ROS/JNK/Bax-mitochondrial apoptotic pathway and caspase-3/-9 activation. Our study indicated that GSDME-dependent pyroptosis is an unrecognized mechanism by which lobaplatin eradicates neoplastic cells, which may have important implications for the clinical application of anticancer therapeutics.

The exogenous excitation requirement and electron-hole recombination are the key elements limiting the application of catalytic therapies. Here a tumor microenvironment (TME)-specific self-triggered thermoelectric nanoheterojunction (Bi 0.5 Sb 1.5 Te 3 /CaO 2 nanosheets, BST/CaO 2 NSs) with self-built-in electric field facilitated charge separation is fabricated. Upon exposure to TME, the CaO 2 coating undergoes rapid hydrolysis, releasing Ca 2+ , H 2 O 2 , and heat. The resulting temperature difference on the BST NSs initiates a thermoelectric effect, driving reactive oxygen species production. H 2 O 2 not only serves as a substrate supplement for ROS generation but also dysregulates Ca 2+ channels, preventing Ca 2+ efflux. This further exacerbates calcium overload-mediated therapy. Additionally, Ca 2+ promotes DC maturation and tumor antigen presentation, facilitating immunotherapy. It is worth noting that the CaO 2 NP coating hydrolyzes very slowly in normal cells, releasing Ca 2+ and O 2 without causing any adverse effects. Tumor-specific self-triggered thermoelectric nanoheterojunction combined catalytic therapy, ion interference therapy, and immunotherapy exhibit excellent antitumor performance in female mice. The exogenous excitation requirement and electron-hole pair recombination are the key factors limiting the application of catalytic therapies. Here, the authors address these limitations by designing a tumor microenvironment-specific self-triggered thermoelectric nanoheterojunction with a self-built-in electric field that facilitates charge separation for cancer treatment.

The Southern Depression of the Southwest Taiwan Basin is an ENE‐trending wide rift in the northeastern South China Sea margin. Though known as highly thinned, the maximum degree of crustal extension remains unclear. Here, we present three NW‐trending multi‐channel seismic profiles crossing the depression askew, and another profile traversing it, all of which image the basement and Moho clearly. The basement deepens toward the rift axis while the Moho shoals toward the axis, indicating significant crustal thinning. Faults appear with only small throws and are usually untraceable to depth. As the integral fault offset seems insufficient to match the horizontal crustal extension, the high crustal thinning is mainly accommodated by detachment faults. Only small‐scale post‐rift magmatic bodies and sporadic sills are observed, and syn‐rift magmatism is poor. The depression shows a recumbent V‐shaped valley opening to the northeast with the width increasing from 50 km on the southwestern profile to 96 km on the northeastern profile. Along the valley axis, the crust thins from 8.1 to 3.6 km and more thinner to the northeast, demonstrating enhanced extensional degree toward the northeast. A unique conch‐shaped package (up to ∼2 s two‐way travel time thick) with moderately coherent reflections is imaged atop the axial mantle on the northeastern profile. It was possibly formed by mantle exhumation, syn‐rift sedimentary uplift, or volcanic eruption. All these possibilities indicate that the crust probably broke up there, which represents a special style of crustal thinning different from other magma‐poor margins. Plain Language Summary Crustal breakup in passive continental margin is often observed in the continent‐ocean transition zone. It has also been speculated to occasionally occur in several intra‐continental rifts such as the Zhongjiannan Basin in the western South China Sea (SCS) and the Porcupine Basin in the southwestern Ireland, but clear seismic imaging is currently lacking. This study provides well‐imaged multi‐channel seismic profiles and shows a special conch‐shaped reflection package with a dome top in the Southwest Taiwan Basin of the northeastern SCS margin. The reflection package consists of several coherent reflections and is similar to the structures of exhumed serpentinized mantle, multi‐phase volcanic eruptions, or syn‐rift sedimentary uplift. All these possibilities suggest that the crust in the Southwest Taiwan Basin probably broke up during rifting. Key Points In the Southern Depression of the Southwest Taiwan Basin, a V‐shaped rift valley opening to the northeast is observed Along the rift valley axis, the continental crust thins significantly from the southwest toward the opening side A conch‐shaped reflection package with several coherent reflections exists at the opening side, representing likely crustal breakup

In real-world scenarios, the rotational speed of bearings is variable. Due to changes in operating conditions, the feature distribution of bearing vibration data becomes inconsistent, which leads to the inability to directly apply the training model built under one operating condition (source domain) to another condition (target domain). Furthermore, the lack of sufficient labeled data in the target domain further complicates fault diagnosis under varying operating conditions. To address this issue, this paper proposes a spatiotemporal feature fusion domain-adaptive network (STFDAN) framework for bearing fault diagnosis under varying operating conditions. The framework constructs a feature extraction and domain adaptation network based on a parallel architecture, designed to capture the complex dynamic characteristics of vibration signals. First, the Fast Fourier Transform (FFT) and Variational Mode Decomposition (VMD) are used to extract the spectral and modal features of the signals, generating a joint representation with multi-level information. Then, a parallel processing mechanism of the Convolutional Neural Network (SECNN) based on the Squeeze-and-Excitation module and the Bidirectional Long Short-Term Memory network (BiLSTM) is employed to dynamically adjust weights, capturing high-dimensional spatiotemporal features. The cross-attention mechanism enables the interaction and fusion of spatial and temporal features, significantly enhancing the complementarity and coupling of the feature representations. Finally, a Multi-Kernel Maximum Mean Discrepancy (MKMMD) is introduced to align the feature distributions between the source and target domains, enabling efficient fault diagnosis under varying bearing conditions. The proposed STFDAN framework is evaluated using bearing datasets from Case Western Reserve University (CWRU), Jiangnan University (JNU), and Southeast University (SEU). Experimental results demonstrate that STFDAN achieves high diagnostic accuracy across different load conditions and effectively solves the bearing fault diagnosis problem under varying operating conditions.

Background The involvement of ferroptosis in ulcerative colitis (UC) is increasingly acknowledged. Several investigations have revealed the various mechanisms by which the farnesoid X receptor (FXR) inhibits ferroptosis in certain diseases; however, its potential modulation of ferroptosis in UC remains unexplored. Methods The characteristics of FXR expression in colitis were evaluated in the GEO database, patient specimens, and mice with DSS-induced colitis. The role of FXR in ferroptosis was investigated by treating colitis mice with the intestine-restricted FXR agonist fexaramine (Fex) intragastrically. In vitro, Caco-2 cells challenged with RSL3 were used to study the role of FXR in modulating ferroptosis in intestinal epithelial cells (IECs). Results Fex significantly alleviated symptoms and impeded ferroptosis in mice with DSS-induced colitis. In vitro, Fex rescued Caco-2 cells from RSL3-induced ferroptosis. Mechanistically, FXR was capable of binding to the promoter region of SLC7A11 and upregulated the transcription of SLC7A11, which is beneficial for the synthesis of GSH. Knockdown of SLC7A11 partially abrogated the therapeutic effects of Fex, albeit incompletely. Further investigations revealed that FXR can also increase the protein stability of GPX4 by upregulating the deubiquitinase OTUB1. Conclusion This study highlights that FXR exerts therapeutic effects against colitis by antagonizing ferroptosis via transactivation of SLC7A11 and increasing GPX4 stability. These results suggest that FXR may be a therapeutic target for treating colitis by antagonizing ferroptosis. Graphical Abstract

Background The gasdermins (GSDMs) family is proposed to be pore-forming effector proteins that cause cell membrane permeabilization and pyroptosis. Despite our increasing knowledge of GSDMD, GSDME and GSDMB, the biological functions and the regulation of GSDM expression and activation remain elusive for most GSDMs. In this study, we analyzed the molecular characteristics and oncogenic role of GSDM family genes systematically. Methods TCGA, CCLE, cBioPortal, GEPIA, CellMiner and BioGRID databases were utilized in this study. Immunohistochemical analysis and a series of in vitro experiments were conducted. Results We found that, in cancer, GSDM genes and their expressions extensively changed, which were associated with patient survival. The expression of GSDMs was widely associated with cancer-related pathways, drug resistance, immune subtypes, tumor microenvironment and cancer cell stemness. However, an intra- and inter-cancer heterogeneity was discovered regarding the corresponding GSDM gene. We found that GSDMA and GSDMB regulated drug resistance to the opposite direction of GSDME. In colorectal cancer, GSDME might be a positive regulator in cell invasion and metastasis through cell migration and angiogenesis, while GSDMA, GSDMB and GSDMD might be a negatively regulator of cell migration. Conclusions GSDM family genes might play important roles in cancer other than pyroptosis. We suggest more efforts be made to investigate the GSDM family and each GSDM gene be studied as an entity in each type of cancer.

Background Centrosomal protein of 55 kDa (CEP55) overexpression has been linked to tumor stage, aggressiveness of the tumor, poor prognosis, and metastasis. This study aims to elucidate the action of CEP55 in ovarian cancer (OC) and the regulation by the alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 (ALKBH5)/Forkhead box protein P2 (FOXP2) axis. Methods Differentially expressed genes in OC were identified using in silico identification, followed by prognostic value assessment. Lentiviral vectors were constructed to downregulate CEP55 in OC cells, and colony formation, EdU, TUNEL, flow cytometry, Transwell assays, and Phalloidin staining were conducted. Transcription factors regulating CEP55 were predicted and verified, and rescue experiments were performed. The effect of ALKBH5-mediated demethylation on FOXP2 mRNA stability and OC cell cycle and EMT were analyzed. Results High expression of CEP55 in OC was linked to unsatisfactory prognosis of patients. Knockdown of CEP55 repressed proliferation, invasiveness, and epithelial-mesenchymal transition (EMT) while inducing apoptosis and cell cycle arrest in OC cells. FOXP2 bound to the promoter of CEP55 to repress CEP55 transcription. FOXP2 regulated transcriptional repression of CEP55 to impede the malignant progression of OC and inhibit tumor metastasis. ALKBH5-mediated demethylation modification induced mRNA degradation of FOXP2. Knockdown of ALKBH5 induced cell cycle arrest and inhibited EMT in OC cells. Conclusions ALKBH5 hinders FOXP2-mediated transcriptional repression of CEP55 to promote the malignant progression of OC via cell cycle and EMT.

Our previous study indicated that colon cancer cells varied in sensitivity to pharmacological farnesoid X receptor (FXR) activation. Herein, we explore the regulatory mechanism of FXR in colorectal cancer (CRC) development and aim to design effective strategies of combined treatment based on the regulatory axis. We found that the expression of FXR was negatively correlated with enhancer of zeste homolog 2 (EZH2) in colon cancer tissues. EZH2 transcriptionally suppressed FXR via H3K27me3. The combination of FXR agonist OCA plus EZH2 inhibitor GSK126 acted in a synergistic manner across four colon cancer cells, efficiently inhibiting clonogenic growth and invasion in vitro, retarding tumor growth in vivo, preventing the G0/G1 to S phase transition, and inducing caspase-dependent apoptosis. Benign control cells FHC were growth-arrested without apoptosis induction, but retained long-term proliferation and invasion capacity. Mechanistically, the drug combination dramatically accelerated FXR nuclear location and cooperatively upregulated caudal-related homeobox transcription factor 2 (CDX2) expression. The depletion of CDX2 antagonized the synergistic effects of the drug combination on tumor inhibition. In conclusion, our study demonstrated histone modification-mediated FXR silencing by EZH2 in colorectal tumorigenesis, which offers useful evidence for the clinical use of FXR agonists combined with EZH2 inhibitors in combating CRC.

Magnetic levitation (MagLev) is a promising density-based analytical technique with numerous applications. Several MagLev structures with different levels of sensitivity and range have been studied. However, these MagLev structures can seldom satisfy the different performance requirements simultaneously, such as high sensitivity, wide measurement range, and easy operation, which have prevented them from being widely used. In this work, a tunable MagLev system was developed. It is confirmed by numerical simulation and experiments that this system possesses a high resolution down to 10−7 g/cm3 or even higher compared to the existing systems. Meanwhile, the resolution and range of this tunable system can be adjusted to meet different requirements of measurement. More importantly, this system can be operated simply and conveniently. This bundle of characteristics demonstrates that the novel tunable MagLev system could be handily applied in various density-based analyses on demand, which would greatly expand the ability of MagLev technology.