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Overexpression of NPM1 can promote the growth and proliferation of various tumor cells. However, there are few studies on the comprehensive analysis of NPM1 in lung adenocarcinoma (LUAD). TCGA and GEO data sets were used to analyze the expression of NPM1 in LUAD and clinicopathological analysis. The GO/KEGG enrichment analysis of NPM1 co-expression and gene set enrichment analysis (GSEA) were performed using R software package. The relationship between NPM1 expression and LUAD immune infiltration was analyzed using TIMER, GEPIA database and TCGA data sets, and the relationship between NPM1 expression level and LUAD m6A modification and glycolysis was analyzed using TCGA and GEO data sets. NPM1 was overexpressed in a variety of tumors including LUAD, and the ROC curve showed that NPM1 had a certain accuracy in predicting the outcome of tumors and normal samples. The expression level of NPM1 in LUAD is significantly related to tumor stage and prognosis. The GO/KEGG enrichment analysis indicated that NPM1 was closely related to translational initiation, ribosome, structural constituent of ribosome, ribosome, Parkinson disease, and RNA transport. GSEA showed that the main enrichment pathway of NPM1-related differential genes was mainly related to mTORC1 mediated signaling, p53 hypoxia pathway, signaling by EGFR in cancer, antigen activates B cell receptor BCR leading to generation of second messengers, aerobic glycolysis and methylation pathways. The analysis of TIMER, GEPIA database and TCGA data sets showed that the expression level of NPM1 was negatively correlated with B cells and NK cells. The TCGA and GEO data sets analysis indicated that the NPM1 expression was significantly correlated with one m6A modifier related gene (YTHDF2) and five glycolysis related genes (ENO1, HK2, LDHA, LDHB and SLC2A1). NPM1 is a prognostic biomarker involved in immune infiltration of LUAD and associated with m6A modification and glycolysis. NPM1 can be used as an effective target for diagnosis and treatment of LUAD.

Purpose Hepatocellular carcinoma (HCC) is a complicated disease with low survival rate due to frequent recurrence and the lack of efficient therapies. For advanced HCC, sorafenib, as the only approved first-line drug for HCC, improves the survival to some extent, but depressingly with severe adverse effects and emerging resistance conditions, which cause a poor prognosis. Ferroptosis is a new recognized way of non-apoptosis-regulated cell death, characterized by the iron-dependent accumulation of lipid hydroperoxides, showing a tremendous promising in the therapy of cancer, especially in HCC. To provide ideas for the diagnosis and treatment of HCC, we summarized the role of ferroptosis in HCC. Methods The relevant literature from PubMed is reviewed in this article. Results Interestingly enough, investigators have found sorafenib can induce ferroptosis in HCC. Moreover, recent researches reported increasing pathways and mechanisms related to ferroptosis in HCC such as TP53 and Rb, and strategies to improve sorafenib resistance by targeting ferroptosis. In addition, other drugs were reported to induce ferroptosis in HCC such as erastin and showed good efficacy in vivo and in vitro. Conclusion In this review, we summarize pathways and mechanisms of ferroptosis in HCC and other digestive system neoplasms such as gastric cancer, pancreatic cancer and colorectal cancer and point out the trends of ferroptosis in HCC.

The seasonal Predictability Barrier (PRB) and Persistence Barrier (PEB) in the El Niño‐Southern Oscillation (ENSO) phenomenon are of recent interest, yet the distinction between the PRB in observations and PEB in ensemble forecast models remains unexplored. Using observational and North American Multimodel Ensemble data since the 1980s, we examined the seasonal PRB and PEB, focusing on intensity, timing, decadal variations, and spatial patterns. Although the intensity of the ENSO spring PRB in dynamic models is notably lower than the spring PEB intensity, the temporal variations, spatial patterns and barrier timing of the PRB and PEB are similar. The chaotic nature of ENSO systems exhibits comparable decadal variations and spatial patterns to the seasonal PEB and PRB, suggesting potential control by chaotic behavior for both seasonal PRB and PEB. Hence, the seasonal PEB of ENSO can still provide useful benchmarks for the predictability study of ENSO in dynamic models. Plain Language Summary Enhancing understanding of the predictability of the El Niño‐Southern Oscillation (ENSO) is crucial for improving seasonal forecasting and managing extreme climate impacts. This study examines the seasonal Predictability Barrier (PRB) and Persistence Barrier (PEB) of ENSO using observational and dynamic prediction model data to analyze their intensity, timing, long‐term trends, and spatial distribution. Our analysis reveals a notable decrease in the intensity of the seasonal PRB of ENSO in dynamic models compared to the PEB. A marked increase in the strength of ENSO seasonal PRB and PEB was noted around the 2000s, potentially impacting ENSO predictability in the twenty‐first century. The central and eastern tropical Pacific regions are key areas for seasonal PRB and PEB occurrences. Decadal fluctuations in the chaotic nature of ENSO systems align with those of the seasonal PRB and PEB, implying that these barriers are predominantly influenced by the chaotic dynamics of ENSO systems. Key Points The spring Predictability Barrier (PRB) in dynamic model exhibits a notably weaker intensity than the spring Persistence Barrier (PEB) The temporal variations, spatial patterns and barrier timing of seasonal PRB and PEB in the tropical Pacific are similar since 1980s The chaotic characteristics of El Niño‐Southern Oscillation systems leads to the similarity between seasonal PRB and PEB

Protonic ceramic electrochemical cells hold promise for operation below 600 °C (refs. 1 , 2 ). Although the high proton conductivity of the bulk electrolyte has been demonstrated, it cannot be fully used in electrochemical full cells because of unknown causes 3 . Here we show that these problems arise from poor contacts between the low-temperature processed oxygen electrode–electrolyte interface. We demonstrate that a simple acid treatment can effectively rejuvenate the high-temperature annealed electrolyte surface, resulting in reactive bonding between the oxygen electrode and the electrolyte and improved electrochemical performance and stability. This enables exceptional protonic ceramic fuel-cell performance down to 350 °C, with peak power densities of 1.6 W cm −2 at 600 °C, 650 mW cm −2 at 450 °C and 300 mW cm −2 at 350 °C, as well as stable electrolysis operations with current densities above 3.9 A cm −2 at 1.4 V and 600 °C. Our work highlights the critical role of interfacial engineering in ceramic electrochemical devices and offers new understanding and practices for sustainable energy infrastructures. A simple acid treatment can improve high-temperature annealed electrolyte surfaces, resulting in improved performance and stability at lower temperatures for protonic ceramic fuel/electrolysis cells, offering new understanding for sustainable energy infrastructures.

The initial density distribution provides a basis for understanding the complete evolution of cosmological density fluctuations. While reconstruction in our local Universe exploits the observations of galaxy surveys with large volumes, observations of high-redshift galaxies are performed with a small field of view and therefore can hardly be used for reconstruction. Here, we propose reconstructing the initial density field using the H i 21 cm and CO line intensity maps from the epoch of reionization. Observations of these two intensity maps provide complementary information on the density field—the H i 21 cm field is a proxy of matter distributions in the neutral regions, while the CO line intensity maps are sensitive to the high-density, star-forming regions that host the sources for reionization. Technically, we employ the conjugate gradient method and develop the machinery for minimizing the cost function for the intensity mapping observations. Analytical expressions for the gradient of cost function are derived explicitly. We show that the resimulated intensity maps match the input maps of mock observations using semi-numerical simulations of reionization with an rms error ≲7% at all stages of reionization. This reconstruction is also robust with an rms error of ∼10% when an optimistic level of shot noise is applied to the CO map or white noise at the level of ≲10% of the standard deviation is applied to each map. Our proof-of-concept work demonstrates the robustness of the reconstruction method, thereby providing an effective technique for reconstructing the cosmological initial density distribution from high-redshift observations.

The cracks in a rock tend to initiate, propagate, and coalesce under loading. Based on the digital image correlation (DIC) method, uniaxial compression tests are carried out on rock-like specimens with various arrangements of two parallel cracks. The full-field strain and failure features of the rock-like materials are observed and analysis by a self-developed code. Two process zones are defined according to the differences between the shear strain field and the tensile strain field: a shear process zone and a tensile process zone. The following results are obtained in this study. (1) Three coalescence modes can be observed using the DIC method: a shear coalescence mode, a tensile coalescence mode, and a mixed coalescence mode. (2) At the microscopic level, the bridge angle and crack arrangement affect the formation of the process zone; at the macroscopic level, they determine the crack propagation path and the failure mode. (3) The peak strength of the rock-like specimen is related to the crack inclination angle and the bridge angle. (4) Numerical modeling by the expanded distinct element method and the strain strength criterion simulates the different coalescence modes of the experimental study efficiently.

AbstractObjectiveTo evaluate the efficacy and safety of standard term (12 months) or long term (>12 months) dual antiplatelet therapy (DAPT) versus short term (<6 months) DAPT after percutaneous coronary intervention (PCI) with drug-eluting stent (DES).DesignSystematic review and network meta-analysis.Data sourcesRelevant studies published between June 1983 and April 2018 from Medline, Embase, Cochrane Library for clinical trials, PubMed, Web of Science, ClinicalTrials.gov, and Clinicaltrialsregister.eu.Review methodsRandomised controlled trials comparing two of the three durations of DAPT (short term, standard term, and long term) after PCI with DES were included. The primary study outcomes were cardiac or non-cardiac death, all cause mortality, myocardial infarction, stent thrombosis, and all bleeding events.Results17 studies (n=46 864) were included. Compared with short term DAPT, network meta-analysis showed that long term DAPT resulted in higher rates of major bleeding (odds ratio 1.78, 95% confidence interval 1.27 to 2.49) and non-cardiac death (1.63, 1.03 to 2.59); standard term DAPT was associated with higher rates of any bleeding (1.39, 1.01 to 1.92). No noticeable difference was observed in other primary endpoints. The sensitivity analysis revealed that the risks of non-cardiac death and bleeding were further increased for ≥18 months of DAPT compared with short term or standard term DAPT. In the subgroup analysis, long term DAPT led to higher all cause mortality than short term DAPT in patients implanted with newer-generation DES (1.99, 1.04 to 3.81); short term DAPT presented similar efficacy and safety to standard term DAPT with acute coronary syndrome (ACS) presentation and newer-generation DES placement. The heterogeneity of pooled trials was low, providing more confidence in the interpretation of results.ConclusionsIn patients with all clinical presentations, compared with short term DAPT (clopidogrel), long term DAPT led to higher rates of major bleeding and non-cardiac death, and standard term DAPT was associated with an increased risk of any bleeding. For patients with ACS, short term DAPT presented similar efficacy and safety with standard term DAPT. For patients implanted with newer-generation DES, long term DAPT resulted in more all cause mortality than short term DAPT. Although the optimal duration of DAPT should take personal ischaemic and bleeding risks into account, this study suggested short term DAPT could be considered for most patients after PCI with DES, combining evidence from both direct and indirect comparisons.Systematic review registrationPROSPERO CRD42018099519.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a multisystem autoimmune disease with small-vessel involvement. In AAV, microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) are major clinicopathologic variants. In addition, myeloperoxidase (MPO) and proteinase 3 (PR3) are major target antigens. The objective of the study was to explore the predictive factors for long-term survival in AAV patients. A multicenter retrospective study was carried out on 407 patients between 2005 and 2020. Clinical parameters were obtained from laboratory tests including the ANCA types, antinuclear antibody (ANA), extractable nuclear antigen (ENA), anti-streptolysin O (ASO), glomerular filtration rate (GFR), and the laboratory examinations for the blood routine, liver function, renal function, and immunity, etc. The data for clinical parameters were collected from electronic medical records (EMRs), and the data for patient survival were acquired through regular follow-up. The association of clinical parameters with overall survival (OS) along with 3-year and 5-year survival rates was analyzed, and the nomogram as a predictive model was established according to the analysis results. In the present study, 336 (82.6%) patients and 46 (11.3%) patients were diagnosed with MPA and GPA, respectively. The mean and median OS for all the patients were 2,285 and 2,290 days, respectively. The 1-year, 3-year, 5-year, and 10-year cumulative survival rates for all the patients were 84.2%, 76.3%, 57.2%, and 32.4%, respectively. Univariate and multivariate survival analyses indicated that the independent prognostic factors included age, pathological categories (MPA, GPA, and other types), serum ANCA types (negative or positive for MPO and/or PR3), ANA, ASO, GFR, lymphocyte, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP), and these clinical parameters except for ASO were used to construct a nomogram. The nomogram for 3-year and 5-year survival rates had a C-index of 0.721 (95% CI 0.676-0.766). The calibration curves showed that the predicted values of the nomogram for 3-year and 5-year survival rates were generally consistent with practical observed values, and decision curve analysis (DCA) further demonstrated the practicability and accuracy of the predictive model. Laboratory tests at diagnosis have great significance in the prediction of long-term survival in AAV patients.

Photoacoustic tomography (PAT), a promising medical imaging method that combines optical and ultrasound techniques, has been developing for decades mostly in preclinical application. A recent trend is to utilize the economical laser source to develop a low-cost sensing and imaging system, which aims at an affordable solution in clinical application. These low-cost laser sources have different modulation modes such as pulsed modulation, continuous modulation and coded modulation to generate different profiles of PA signals in photoacoustic (PA) imaging. In this paper, we review the recent development of the photoacoustic sensing and imaging based on the economical laser sources such as laser diode (LD) and light-emitting diode (LED) in different kinds of modulation types, and discuss several representative methods to improve the performance of such imaging systems based on low-cost laser sources. Finally, some perspectives regarding the future development of portable PAT systems are discussed, followed by the conclusion.

The Ross Ice Shelf Polynya (RISP) is one of the primary production sites of the High Salinity Shelf Water (HSSW), the precursor of Antarctic Bottom Water (AABW) that drives the lower limb of global meridional overturning circulation. Utilizing a multi‐platform historical data set gathered over the western Ross Sea continental shelf, this study employs a box model to estimate heat and salt budgets in the western RISP and Ross Ice Shelf Cavity (RISC) system. Our analysis identifies three dominant controls on heat and salt budgets in the western RISC: cavity‐polynya exchange (EX), glacial basal melting (GM), and subglacial discharge (SD). The rate of SD is estimated at 87.0 Gt·yr−1, higher compared with previous studies. This study highlights the role of subglacial discharge in modulating water mass evolution in Antarctic marginal seas, a component that requires incorporation in future climate models.