Multilayer PZT thin films composed of Pb
1.10
(Zr
0.52,
Ti
0.48
)O
3
and Pb
1.25
(Zr
0.52,
Ti
0.48
)O
3
films were deposited on Pt(111)/Ti/SiO
2
/Si(100) substrate coated by Pb
1.10
(Zr
0.52,
Ti
0.48
...)O
3
buffer layer using RF magnetron sputtering. The effect of variation of layer numbers of Pb
1.10
(Zr
0.52,
Ti
0.48
)O
3
and Pb
1.25
(Zr
0.52,
Ti
0.48
)O
3
thin films in multilayer PZT films was investigated. X-ray diffraction (XRD) analysis indicates all PZT films possess pure perovskite phase and (111) preferred orientation. For multilayer thin films, dense perovskite microstructures without obvious defects were observed using scanning electron microscope (SEM). Optimal dielectric properties with a
ε
r
of 1092 and a tan
δ
of 0.04 at 1 kHz were obtained in the PZT film with the maximum layer numbers (8-layer film, namely L-8). Well-saturated
P
–
E
was observed in L-8 film by a standard ferroelectric test system (
P
r
= 26.1 µC/cm
2
,
E
c
= 60.1 kV/cm). Moreover, a Lower leakage current density (
J
= 5.49 × 10
−6
A/cm
2
at 117 kV) was achieved in sample L-8.
Tool wear is a noteworthy problem in the process of shield tunneling, and the degree of wear varies with stratum. The sand‐pebble strata in Beijing are typically mechanically unstable. However, many ...subways are buried wholly or partially in sand‐pebble strata. Taking the Beijing New Airport line tunneling project as research background, this study evaluated the wear characteristics of the multiconfiguration rippers of a 9‐m‐diameter spoke‐type shield tunneling machine in a sand‐pebble stratum. The wear values of five ripper teeth and ripper flanks were analyzed based on field‐measured data from the Beijing New Airport line project. As the analytical results show, the wear value generally increases as the installation radius enlarges with the rise of cutting trace length. The wear of the 190‐rippers was divided into five categories: pedestal wear, ripper teeth collapse, uniform wear, ripper teeth falling off and ripper flank wear. Uniform wear of the ripper teeth and ripper flank wear were the two abrasion types of the 190‐rippers. The teeth of the 155‐rippers mostly maintained their cutting capacity under the protection of the 190‐rippers. A wear prediction model of linear fitting field data was developed for a 190‐ripper face to obtain the optimum shield driving distance in the sand‐pebble stratum. The average wear coefficients of the 190‐ripper before and after replacement matched well, being 0.045 and 0.066 mm/km, respectively. The results of this study provide a theoretical reference for tool wear prediction in shield construction under similar geological conditions.
This study investigated tool wear values in shield machines based on the engineering background of the Beijing Metro New Airport line and field measurements of cutter wear. The types of abrasiveness of the 190‐ and 155‐ripper are then summarized based on‐site photos. This study statistically analyzed the wear values and wear mechanisms of rippers and estimated the optimum distance of replacement for rippers in the sand‐pebble strata in Beijing by using the JTS model.
Bladder cancer (BCA) is the most common urinary tumor, but its pathogenesis is unclear, and the associated treatment strategy has rarely been updated. In recent years, a deeper understanding of tumor ...epigenetics has been gained, providing new opportunities for cancer detection and treatment.
We identified prognostic methylation sites based on DNA methylation profiles of BCA in the TCGA database and constructed a specific prognostic subgroup.
Based on the consistent clustering of 402 CpGs, we identified seven subgroups that had a significant association with survival. The difference in DNA methylation levels was related to T stage, N stage, M stage, grade, sex, age, stage and prognosis. Finally, the prediction model was constructed using a Cox regression model and verified using the test dataset; the prognosis was consistent with that of the training set.
The classification based on DNA methylation is closely related to the clinicopathological characteristics of BCA and determines the prognostic value of each epigenetic subtype. Therefore, our findings provide a basis for the development of DNA methylation subtype-specific therapeutic strategies for human bladder cancer.
Metastatic pheochromocytoma/paraganglioma (MPP) is a rare endocrine tumor that originates from extra-adrenal chromaffin cells such as the paraganglia cells of sympathetic and parasympathetic nerves. ...It usually causes multiple solid tumors and exhibits strong aggressiveness with poor prognosis, with a reported 5-year survival rate of less than 50%. Cases of brain and retroperitoneal metastases at the initial diagnosis have not yet been reported. We report a 41-year-old male patient initially diagnosed with MPP in the brain and retroperitoneum who underwent multi-disciplinary collaborative surgery and simultaneous removal of two tumors at our center. Postoperative pathology revealed infiltrative growth of a skull base tumor. The patient chose to receive the tyrosine kinase inhibitor sunitinib as a targeted treatment. A 3-month follow-up after surgery showed that the patient recovered well without signs of metastasis or recurrence. We present multi-disciplinary surgery under similar circumstances for enhanced treatment and postoperative management. The patient demonstrates a favorable prognosis during postoperative follow-up, indicating that simultaneous multidisciplinary surgery may offer greater benefits for MPP patients.
•This report describes a rare case of metastatic pheochromocytoma/paraganglioma (MPP) where the patient was initially diagnosed with two lesions.•Multi-disciplinary surgery was performed to simultaneously resect both lesions.•The cutting edge of the head tumor was positive.•Patients who received targeted sunitinib therapy showed normal endocrine levels and no signs of recurrence during follow-up.
Gap junctions are present in most tissues and play essential roles in various biological processes. However, we know surprisingly little about the molecular mechanisms underlying gap junction ...formation. Here, we uncover the essential role of a conserved EGF- and laminin-G-domain-containing protein nlr-1/CASPR in the regulation of gap junction formation in multiple tissues across different developmental stages in C. elegans. NLR-1 is located in the gap junction perinexus, a region adjacent to but not overlapping with gap junctions, and forms puncta before the clusters of gap junction channels appear on the membrane. We show that NLR-1 can directly bind to actin to recruit F-actin networks at the gap junction formation plaque, and the formation of F-actin patches plays a critical role in the assembly of gap junction channels. Our findings demonstrate that nlr-1/CASPR acts as an early stage signal for gap junction formation through anchoring of F-actin networks.
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•NLR-1 locates in the gap junction perinexus to regulate gap junction formation•NLR-1 can recruit F-actin networks at the gap junction formation plaque•The formation of F-actin patches plays a critical role in the assembly of gap junctions•nlr-1 and its mammalian homolog can form connexin-based gap junctions in C. elegans
Meng et al. reveal the role of the conserved EGF- and laminin-G-domain-containing protein nlr-1/CASPR in control of the formation of gap junctions in multiple tissues across different developmental stages and show that NLR-1 forms gap junction through recruiting F-actin networks at the gap junction formation plaque
The regulatory role of ferroptosis in malignant tumours has been recently demonstrated. However, the potential roles of ferroptosis mediation patterns in bladder cancer remain elusive.
The ...ferroptosis mediation patterns of 889 bladder cancer samples were comprehensively evaluated based on ferroptosis-related genes. The underlying correlations between these mediation patterns and multi-omic characteristics of bladder cancer were systematically analysed. The ferroptosis mediation patterns of individual samples were quantified by ferropscore using the principal component analysis algorithm. The typical ferroptosis-related genes with prognostic roles were further randomly validated using immunohistochemical staining, real-time polymerase chain reaction and western blotting.
Three different ferroptosis mediation patterns were identified. The abundance of infiltration of 23 immune cells was different among the three mediation patterns. The quantification of ferroptosis mediation patterns in individual samples served as a promising tool for predicting patient survival outcomes; immune cell infiltration abundance; tumour mutation burden; oncogenic mutation status and tumour grade, stage and molecular subtypes. Low ferropscore combined with high tumour mutation burden was associated with the best survival prognosis. Expressions of PD-L1 (
< 0.001), PD-1 (
= 0.002) and CTLA-4 (
= 0.003) were all significantly upregulated in the high ferropscore group. Low ferropscores also predicted good immunotherapy response for anti-CTLA4 strategy. The mRNA and protein levels of FADS2, a typical ferroptosis-related gene used in the study, were higher in bladder cancer cell lines than in controlled SV-HUC-1 cells. In addition, immunohistochemical staining revealed significantly higher expression levels of FADS2 in human bladder cancer tumour tissues than in normal tissues.
This study identified three distinct ferroptosis mediation patterns in bladder cancer. Quantification of ferroptosis mediation patterns in individual samples may help to improve the understanding of multiomic characteristics and guide future immunotherapy responses to bladder cancer.
Synapse elimination occurs in development, plasticity, and disease. Although the importance of synapse elimination has been documented in many studies, the molecular mechanisms underlying this ...process are unclear. Here, using the development of C. elegans RME neurons as a model, we have uncovered a function for the apoptosis pathway in synapse elimination. We find that the conserved apoptotic cell death (CED) pathway and axonal mitochondria are required for the elimination of transiently formed clusters of presynaptic components in RME neurons. This function of the CED pathway involves the activation of the actin-filament-severing protein, GSNL-1. Furthermore, we show that caspase CED-3 cleaves GSNL-1 at a conserved C-terminal region and that the cleaved active form of GSNL-1 promotes its actin-severing ability. Our data suggest that activation of the CED pathway contributes to selective elimination of synapses through disassembly of the actin filament network.
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•The cell death (CED) pathway is required for synapse elimination•Axonal mitochondria regulate synapse elimination through the CED pathway in vivo•GSNL-1 acts downstream of the CED pathway in synapse elimination•Cleavage of GSNL-1 by CED-3 induces F-actin disassembly and synapse elimination
Meng et al. find that activation of the cell death pathway in C. elegans neurons contributes to selective elimination of synapses through disassembly of the actin filament network.
To comprehensively analyze N6-methyladenosine modification patterns in bladder tumors and to further systematically explore the inherent relationships between these modification patterns and ...multiomic tumor characteristics.
A total of 901 bladder tumor samples, including 405 samples from TCGA database, 188 samples from GSE13507 and 308 samples from GSE32894, were included in this systematic analysis. The N6-methyladenosine modification patterns were identified utilizing unsupervised clustering analysis. To quantify N6-methyladenosine modification patterns, the m6Ascore of individual sample was developed using principal component analysis algorithms. Relationships among immune infiltration, tumor mutation burden, various clinical characteristics, molecular subtypes, and the m6Ascore were systematically analyzed. The guiding value of m6Ascore in immunotherapy was further validated in an external trial cohort. Genomics of Drug Sensitivity in Cancer expression references were also utilized to perform drug sensitivity analysis for patients with distinct m6A modification patterns.
We determined three different N6-methyladenosine modification patterns for 901 bladder tumors. The quantitative m6Ascore of individual sample derived from N6-methyladenosine modification patterns could play a significant role in predicting overall survival, immune cell infiltration, and classic oncogene mutations. A low m6Ascore combined with high tumor mutation burden indicated better survival outcomes (
< 0.001). A higher m6Ascore also indicated a higher grade, higher T and N stage, elder ages, higher death rate, and higher PD1/PDL1/CTLA4 expressions (
< 0.01). The Basal type tended to exhibit significantly higher m6Ascores than the Luminal and Neuronal subtypes. External immunotherapy cohorts demonstrated that no difference in therapeutic effects was noted between the high and low m6Ascore groups when anti-PD1 immunotherapy was exclusively administered. When anti-PD1 and anti-CTLA4 immunotherapy were simultaneously administered, the high m6Ascore group had a significantly better prognosis than the low m6Ascore group (
< 0.001). High m6A groups were potentially sensitive to various medical treatments including Bleomycin, Bortezomib, Cisplatin, Cyclopamine, Dasatinib, Docetaxe, Rapamycin, and Vinblastine in this study.
This study systematically revealed the important roles of m6A methylation modification patterns in bladder tumors. Detailed quantification of m6A modification patterns could improve our understanding of the bladder tumor microenvironments and could provide guidance for future immunotherapy strategies.
The micro-hydration degree plays a significant role in the strength of cement-sandy soil mixtures. The present study used cement-fiber-sandy soil mixtures in which the fiber was sourced from waste ...cotton/linen-blended fabric to investigate the impacts of different levels of fiber content on the hydration mechanisms and micromechanical performance. Experiments using scanning electron microscopy (SEM) and X-ray powder diffraction (XRD) were carried out to determine how the component content of the different constituents changed with the fiber content (0%, 0.5%, 1.0%, and 1.5%) during the microhydration of the mixtures. A comparative analysis of the strength characteristic curves and the tensile strength variations for different groups of reinforced cement-sandy soil mixtures were conducted by performing triaxial shear tests. The results show that the peak unconfined compressive strength of the mixtures gradually increases with the quartz content of the matrix. The compressive strength of the matrix reaches a peak of 1.5938 MPa, an increase of 24.17%, when the cement and fiber contents were 3% and 1.5% (weight), respectively, with a fiber length of 9 mm. This paper has reference values for the green reinforcement of cement-sandy soil mixtures in the development of underground space.
This study aimed to screen and verify the important prognostic genes related to clear cell renal cell carcinoma (ccRCC) and further analyze their relationship with the immune microenvironment. Gene ...expression profiles from the TCGA-KIRC, GSE46699, GSE36895, and GSE16449 datasets were utilized to explore differentially co-expressed genes in ccRCC. We screened 124 differentially co-expressed genes using a weighted gene co-expression network and differential gene expression analyses. Univariate and multivariate Cox survival analyses revealed that the expressions of genes
, and
were independently related to the overall survival of ccRCC patients. Kaplan-Meier survival analysis was performed, and
was found to have the strongest correlation with the prognosis of ccRCC patients and was consequently selected for further analyses and experimental verification. The results showed that NK cell activation, resting dendritic cells, resting monocytes, and resting mast cells were positively correlated with
expression; CD4
memory activated T cells, regulatory T cells, and M0 macrophages were negatively correlated with
expression. Finally, using western blotting and reverse transcription polymerase chain reaction, we verified that the
protein level was down-regulated in ccRCC samples, which was consistent with the mRNA levels.
was thus identified as diagnosis and prognosis biomarker for ccRCC and is related to the immune microenvironment.