Systematic analysis of PANoptosis-related genes identifies XIAP as a functional oncogene in breast cancer.

BACKGROUND: Breast cancer (BC) is the most prevalent malignant disease affecting women globally. PANoptosis, a novel form of cell death combining features of pyroptosis, apoptosis, and necroptosis, has recently gained attention. However, its precise function in BC and the predictive values of PANoptosis-related genes remain unclear. METHODS: We used the expression data and clinical information of BC tissues or normal breast tissues from public databases, and then successfully developed and verified a BC PANoptosis-related risk model through a combination of univariate Cox regression, least absolute shrinkage and selection operator (LASSO) regression, and Kaplan-Meier (KM) analysis. A nomogram was constructed to estimate survival probability, and its accuracy was assessed using calibration curves. RESULTS: Among 37 PANoptosis-related genes, we identified 4 differentially expressed genes related to overall survival (OS). Next, a risk model incorporating these four PANoptosis-related genes was established. Patients were stratified into low/high-risk groups based on the median risk score, with the low-risk group showing better prognoses and higher levels of immune infiltration. Utilizing the risk score and clinical features, we developed a nomogram to predict 1-, 3- and 5-year survival probability. X-linked inhibitor of apoptosis protein (XIAP) emerged as a potentially risky factor with the highest hazard ratio. In vitro experiments demonstrated that XIAP inhibition enhances the antitumor effect of doxorubicin through the PANoptosis pathway. CONCLUSION: PANoptosis holds an important role in BC prognosis and treatment.

Alteration of chromatin high-order conformation associated with oxaliplatin resistance acquisition in colorectal cancer cells.

Oxaliplatin is a first-line chemotherapy drug widely adopted in colorectal cancer (CRC) treatment. However, a large proportion of patients tend to become resistant to oxaliplatin, causing chemotherapy to fail. At present, researches on oxaliplatin resistance mainly focus on the genetic and epigenetic alterations during cancer evolution, while the characteristics of high-order three-dimensional (3D) conformation of genome are yet to be explored. In order to investigate the chromatin conformation alteration during oxaliplatin resistance, we performed multi-omics study by combining DLO Hi-C, ChIP-seq as well as RNA-seq technologies on the established oxaliplatin-resistant cell line HCT116-OxR, as well as the control cell line HCT116. The results indicate that 19.33% of the genome regions have A/B compartments transformation after drug resistance, further analysis of the genes converted by A/B compartments reveals that the acquisition of oxaliplatin resistance in tumor cells is related to the reduction of reactive oxygen species and enhanced metastatic capacity. Our research reveals the spatial chromatin structural difference between CRC cells and oxaliplatin resistant cells based on the DLO Hi-C and other epigenetic omics experiments. More importantly, we provide potential targets for oxaliplatin-resistant cancer treatment and a new way to investigate drug resistance behavior under the perspective of 3D genome alteration.

Reshifting Na+ from Shoots into Long Roots Is Associated with Salt Tolerance in Two Contrasting Inbred Maize (Zea mays L.) Lines.

Maize, as a glycophyte, is hypersensitive to salinity, but the salt response mechanism of maize remains unclear. In this study, the physiological, biochemical, and molecular responses of two contrasting inbred lines, the salt-tolerant QXH0121 and salt-sensitive QXN233 lines, were investigated in response to salt stress. Under salt stress, the tolerant QXH0121 line exhibited good performance, while in the sensitive QXN233 line, there were negative effects on the growth of the leaves and roots. The most important finding was that QXH0121 could reshift Na+ from shoots into long roots, migrate excess Na+ in shoots to alleviate salt damage to shoots, and also improve K+ retention in shoots, which were closely associated with the enhanced expression levels of ZmHAK1 and ZmNHX1 in QXH0121 compared to those in QXN233 under salt stress. Additionally, QXH0121 leaves accumulated more proline, soluble protein, and sugar contents and had higher SOD activity levels than those observed in QXN233, which correlated with the upregulation of ZmP5CR, ZmBADH, ZmTPS1, and ZmSOD4 in QXH0121 leaves. These were the main causes of the higher salt tolerance of QXH0121 in contrast to QXN233. These results broaden our knowledge about the underlying mechanism of salt tolerance in different maize varieties, providing novel insights into breeding maize with a high level of salt resistance.

Antimicrobial and cleaning effects of ultrasonic-mediated plasma-loaded microbubbles on Enterococcus faecalis biofilm: an in vitro study.

BACKGROUND: Enterococcus faecalis (E. faecalis) is the most frequently isolated bacteria from teeth with root canal treatment failure. This study aims to evaluate the disinfection effect of ultrasonic-mediated cold plasma-loaded microbubbles (PMBs) on 7d E. faecalis biofilm, the mechanical safety and the mechanisms. METHODS: The PMBs were fabricated by a modified emulsification process and the key reactive species, nitric oxide (NO) and hydrogen peroxide (H2O2) were evaluated. The 7d E. faecalis biofilm on human tooth disk was constructed and divided into the following groups: PBS, 2.5%NaOCl, 2%CHX, and different concentrations of PMBs (108 mL-1, 107 mL-1). The disinfection effects and elimination effects were verified with confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). Microhardness and roughness change of dentin after PMBs treatment were verified respectively. RESULTS: The concentration of NO and H2O2 in PMBs increased by 39.99% and 50.97% after ultrasound treatment (p < 0.05) respectively. The CLSM and SEM results indicate that PMBs with ultrasound treatment could remove the bacteria and biofilm components effectively, especially those living in dentin tubules. The 2.5% NaOCl presented an excellent effect against biofilm on dishes, but the elimination effect on dentin tubules is limited. The 2% CHX group exhibits significant disinfection effect. The biosafety tests indicated that there is no significant changes on microhardness and roughness after PMBs with ultrasound treatment (p > 0.05). CONCLUSION: PMBs combined with ultrasound treatment exhibited significant disinfection effect and biofilm removal effect, the mechanical safety is acceptable.

Isolation, Identification and Pollution Prevention of Bacteria and Fungi during the Tissue Culture of Dwarf Hygro (Hygrophila polysperma) Explants.

Microbial contamination causes serious damage in plant tissue culture, and attention is always being paid regarding how to control and prevent the unwanted pollution. Dwarf hygro (Hygrophila polysperma) is a popular ornamental aquatic plant and its tissue culture has been reported, but the microbial pollution and the cure of microbial pollution was unknown. In this study, a number of bacteria and fungi were isolated from contaminants in MS culture media. Based on the 16S rDNA and ITS sequencing, it was identified that fifteen bacteria belong to Bacillus, Enterobacter, Pantoea, Kosakonia, Ensifer and Klebsiella, and three fungi belong to Plectosphaerella, Cladosporium and Peniophora, respectively. In addition, some drugs were further tested to be free of the bacteria and fungi pollution. The results revealed that 10 µg/mL of kanamycin, 5 µg/mL of chloramphenicol, and 0.015625% potassium sorbate could be applied jointly in MS media to prevent the microbial pollution, and the survival rate of H. polysperma explants was highly improved. This study reveals the bacteria and fungi species from the culture pollution of H. polysperma and provides a practical reference for optimizing the tissue culture media for other aquatic plants.

Ultrasound-Activated Nanodroplet Disruption of the Enterococcus faecalis Biofilm in Dental Root Canal.

Conventional methods used to control bacterial biofilm infection in root canals have poor efficacy, causing repeated and chronic infections, which pose a great challenge to clinical treatment. Microbubbles, due to their small size and ultrasound (US)-enhanced cavitation effects, have attracted considerable clinical attention. They possess the potential for therapeutic application in restricted spaces. We address the above problem with a strategy for the restricted space of root canals. Herein, phase-change nanodroplets (P-NDs) exposed to US are combined with common antibacterial drugs to disrupt a 7 day Enterococcus faecalis biofilm in an in vitro human tooth model. Specifically, the preparation of P-NDs is based on secondary cavitation. Their average particle size is ∼144 nm, and the stability is favorable. The clearance effect for the biofilm is notable (the disruption rate of P-NDs + US is 63.1%, P < 0.01), while the effect of an antibacterial in conjunction with 2% chlorhexidine (Chx) is significant (the antibiofilm rate of P-NDs@2% Chx + US is 96.2%, P < 0.001). Furthermore, biocompatibility testing on human periodontal ligament fibroblasts demonstrated that P-NDs are safe. In summary, the strategy that we have proposed is suitable for the removal of biofilms in root canals. Notably, it also has great potential for application in the treatment of bacterial infections in restricted spaces.

Mechanism of Water Content on the Electrochemical Surface Area of the Catalyst Layer in the Proton Exchange Membrane Fuel Cell.

Combined molecular dynamics (MD) simulation and experiment are adopted to gain the mechanism of water content on the electrochemical surface area (ECSA) of the catalyst layer in a proton exchange membrane fuel cell. The morphology of water domains in the catalyst layer has a strong impact on the ECSA via MD simulation. The morphology of the water domains is isolated water clusters at low water content, resulting in the poor ECSA due to the lack of proton transport paths. The transport paths of protons tend to be quickly established with increasing water content during the transition process of the morphology of water domains from isolated water clusters to the water channel network, thereby leading to the rapid increase of the ECSA. However, the slight increase of the ECSA at high water content mainly results from the improved contact area between water domains and Pt particle instead of the formation of new transport paths. In addition, the stronger binding of water molecules and the Pt particle at low temperature results in a higher ECSA.