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Lung adenocarcinoma (LUAD), the most common type of lung cancer, is a leading cause of cancer-related mortality. NT5E, an ecto-5'-nucleotidase enzyme, has been implicated in cancer progression, particularly in efferocytosis. Despite its potential involvement, the prognostic significance of NT5E and relationship with immune cell infiltration in LUAD have not been extensively explored. In this study, we performed a comprehensive analysis to elucidate the expression patterns of NT5E and its prognostic implications in LUAD using data from diverse public databases. Multiple computational algorithms, including CIBERSORT, ESTIMATE, and xCell, were employed to assess the correlation between NT5E expression and immune cell infiltration. We found that NT5E was significantly overexpressed at both the mRNA and protein levels in LUAD tissues. Elevated NT5E expression was significantly linked to multiple clinicopathological factors, including metastasis and pathological stage, and served as a strong predictor of poor prognosis in LUAD patients. Gene Set Enrichment Analysis (GSEA) indicated that NT5E plays a crucial role in regulating immune responses, as evidenced by differential gene expression associated with NT5E levels. A strong positive correlation was observed between NT5E expression and the presence of immune cells, including dendritic cells, macrophages, and CD4+ T cells, as well as the expression of various immune cell markers, suggesting that NT5E may influence the prognosis of LUAD patients by regulating immune cell infiltration. Additionally, drug sensitivity analysis highlights the potential of selumetinib and PD318088, both MEK1/2 inhibitors, to target NT5E in LUAD treatment, suggesting their use as single agents or in combination with other therapies. Collectively, these findings establish NT5E as a promising prognostic biomarker and therapeutic target in LUAD, particularly in the context of immune cell infiltration. [ABSTRACT FROM AUTHOR]

Accurate modeling of lithium-ion battery (LIB) electrode microstructures provides essential references for understanding degradation mechanisms and optimizing materials. Traditional segmentation methods often struggle to accurately capture the complex microstructures of porous LIB electrodes in focused ion beam scanning electron microscopy (FIB-SEM) data. In this work, we develop a deep learning model based on the Swin Transformer to segment FIB-SEM data of a lithium cobalt oxide electrode, utilizing fused secondary and backscattered electron images. The proposed approach outperforms other deep learning methods, enabling the acquirement of 3D microstructure with reduced particle elongated artifacts. Analyses of the segmented microstructures reveal improved electrode tortuosity and pore connectivity crucial for ion and electron transport, emphasizing the necessity of accurate 3D modeling for reliable battery performance predictions. These results suggest a path toward voxel-level degradation analysis through more sensible battery simulation on high-fidelity microstructure models directly twinned from real porous electrodes. [ABSTRACT FROM AUTHOR]

Lithium cobalt oxide (LiCoO2) is an irreplaceable cathode material for lithium‐ion batteries with high volumetric energy density. The prevailing O3 phase LiCoO2 adopts the ABCABC (A, B, and C stand for lattice sites in the close‐packed plane) stacking modes of close‐packed oxygen atoms. Currently, the focus of LiCoO2 development is application at high voltage (>4.55 V versus Li+/Li) to achieve a high specific capacity (>190 mAh g−1). However, cycled with a high cutoff voltage, O3–LiCoO2 suffers from rapid capacity decay. The causes of failure are mostly attributed to the irreversible transitions to H1‐3/O1 phase after deep delithiation and severe interfacial reactions with electrolytes. In addition to O3, LiCoO2 is also known to crystalize in an O2 phase with ABAC stacking. Since its discovery, little is known about the high‐voltage behavior of O2–LiCoO2. Herein, through systematic comparison between electrochemical performances of O3 and O2 LiCoO2 at high voltage, the significantly better stability of O2–LiCoO2 (>4.5 V) than that of O3–LiCoO2 in the same micro‐sized particle morphology is revealed. Combining various characterization techniques and multiscale simulation, the outstanding high‐voltage stability of O2–LiCoO2 is attributed to the high Li diffusivity and ideal mechanical properties. Uniform Li+ distribution and balanced internal stress loading may hold the key to improving the high‐voltage performance of LiCoO2. [ABSTRACT FROM AUTHOR]

The rapid growth of deepfake technology, generating realistic manipulated media, poses a significant threat due to potential misuse. Therefore, effective detection methods are urgently needed to prevent malicious use, as current approaches often focus on single modalities or the simple fusion of audio–visual signals, limiting their accuracy. To solve this problem, we propose a deepfake detection scheme based on bimodal temporal feature prediction, which innovatively introduces the idea of temporal feature prediction into the audio–video bimodal deepfake detection task, aiming at fully exploiting the temporal laws of audio–visual modalities. First, pairs of adjacent audio–video sequence clips are used to construct input quadruples, and a dual-stream network is employed to extract temporal feature representations from video and audio, respectively. A video prediction module and an audio prediction module are designed to capture the temporal inconsistencies within each single modality by predicting future temporal features and comparing them with reference features. Then, a projection layer network is designed to align the audio–visual features, using contrastive loss functions to perform contrastive learning and maximize the differences between real and fake video modalities. Experiments on the FakeAVCeleb dataset demonstrate superior performance with an accuracy of 84.33% and an AUC of 89.91%, outperforming existing methods and confirming the effectiveness of our approach in deepfake detection. [ABSTRACT FROM AUTHOR]

Achieving efficient thermal management urges to exploit high-thermal-conductivity materials to satisfy the boosted demand of heat dissipation. It is critical to adopt standardized characterization protocols to evaluate the intrinsic thermal conductivity of thermal management materials. However, for the most representative laser flash method, the lack of standard measurement methodology and systematic description on the thermal diffusivity and influencing factors has led to significant deviations and confusion of the thermal conduction performance in the emerging thermal management application. Here, the measurement error factors of thermal diffusivity by the common laser flash analyzer (LFA) are discussed. Taking high-thermal-conductivity graphitic film (GF) as a typical case, the key factors are analyzed to guide the measurement protocol of related carbon-based thermal management materials. The basic principle of the LFA measurement, actual pre-processing conditions, instrument parameters setting, and data analysis are elaborated for accurate measurements. Furthermore, the graphene thick films and common isotropic materials are also extended to meet various thermal measurement requirements. Based on the existing practical problems, we propose a feasible test flow to achieve a unified and standardized thermal conductivity measurement, which is beneficial to the rapid development of carbon-based thermal management materials. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PCa) is one of the most fatal human malignancies. The enhanced infiltration of stromal tissue into the PCa tumor microenvironment limits the identification of key tumor‐specific transcription factors and epigenomic abnormalities in malignant epithelial cells. Integrated transcriptome and epigenetic multiomics analyses of the paired PCa organoids indicate that the basic helix‐loop‐helix transcription factor 40 (BHLHE40) is significantly upregulated in tumor samples. Increased chromatin accessibility at the promoter region and enhanced mTOR pathway activity contribute to the elevated expression of BHLHE40. Integrated analysis of chromatin immunoprecipitation‐seq, RNA‐seq, and high‐throughput chromosome conformation capture data, together with chromosome conformation capture assays, indicate that BHLHE40 not only regulates sterol regulatory element‐binding factor 1 (SREBF1) transcription as a classic transcription factor but also links the enhancer and promoter regions of SREBF1. It is found that the BHLHE40‐SREBF1‐stearoyl‐CoA desaturase axis protects PCa cells from ferroptosis, resulting in the reduced accumulation of lipid peroxidation. Moreover, fatostatin, an SREBF1 inhibitor, significantly suppresses the growth of PCa tumors with high expressions of BHLHE40. This study highlights the important roles of BHLHE40‐mediated lipid peroxidation in inducing ferroptosis in PCa cells and provides a novel mechanism underlying SREBF1 overexpression in PCa. [ABSTRACT FROM AUTHOR]

Mitigating interfacial reactions in composite cathode materials remains a key challenge for high-performance all-solid-state batteries (ASSBs), particularly those employing argyrodite-based electrolytes coupled with high-voltage cathodes. Here we study the interfacial chemical reactivity of a Li1−xNi0.5Mn0.3Co0.2O2 (NMC532) and Li6PS5Cl (LPSC) composite using galvanostatic electrochemical impedance spectroscopy, complemented by surface and bulk-sensitive X-ray techniques. By decoupling the time-dependent interfacial degradation from the overall degradation, we show that the redox reaction between NMC532 (oxidant) and LPSC (reductant) is the main origin of degradation. The chemical reaction products share chemical similarities with the ones after the electrochemical reaction. The analysis shows the oxidation activity of transition metals in the cathode composite is Ni4+/3+ > Mn4+/Co3+ > Ni2+/3+. Molecular-dynamics simulations reveal that the reaction is driven by the Li+ diffusion from LPSC to the delithiated-NMC532, leading to the LPSC's structural decomposition and collapse. [ABSTRACT FROM AUTHOR]

Li‐rich cation‐disordered rock‐salt (DRX) materials have emerged as promising candidates for high‐capacity oxide cathodes. Their fluorinated variants have shown improved cycling stability with effectively suppressed oxygen loss. However, a comprehensive understanding of how fluorination impacts the multiscale structure and lithium transportation in DRX remains elusive in experiments. Herein, the neutron total scattering technique in conjunction with the advanced reverse Monte Carlo (RMC) fitting method is employed to characterize the intricate structure of Li1.16Ti0.37Ni0.37Nb0.1O2 (LTNNO) and the fluorinated Li1.2Ti0.35Ni0.35Nb0.1O1.8F0.2 (LTNNOF). Through rigorous statistical analysis, the multiscale structural evolution upon fluorination is quantified from atomic (≤5 Å) to long‐range scale (≈100 Å). The local Li‐rich environments around F induce a modest 2.4% increment in the number of fast Li 0TM (transition metal) channels. Crucially, at a broader scale, the proportion of 0TM channels participating in percolation increases significantly from 2.9% in LTNNO to 8.7% in LTNNOF. Fluorination improves the capacity release mainly through merging isolated fast Li channels into the percolation network. This work experimentally unravels the multiscale mechanism of fluorination‐induced performance improvement in DRX materials and highlights the necessity of adopting an advanced RMC fitting method to obtain a full view of the complex structural features in developing high‐capacity DRX cathodes. [ABSTRACT FROM AUTHOR]

Bimetallic alloys have attracted considerable attention due to the tunable catalytic activity and selectivity that can be different from those of pure metals. Here, we study the superior catalytic behaviors of the Pt3Ni nanowire (NW) over each individual, Pt and Ni NWs during the reverse Water Gas Shift (rWGS) reaction, using density functional theory. The results show that the promoted rWGS activity by Pt3Ni strongly depends on the ensemble effect (a particular arrangement of active sites introduced by alloying), while the contributions from ligand and strain effects, which are of great importance in electrocatalysis, are rather subtle. As a result, a unique Ni–Pt hybrid ensemble is observed at the 110/111 edge of the Pt3Ni NW, where the synergy between Ni and Pt sites is active enough to stabilize carbon dioxide on the surface readily for the rWGS reaction but moderate enough to allow for the facile removal of carbon monoxide and hydrogenation of hydroxyl species. Our study highlights the importance of the ensemble effect in heterogeneous catalysis of metal alloys, enabling selective binding–tuning and promotion of catalytic activity. [ABSTRACT FROM AUTHOR]

Reversible lattice oxygen redox reactions offer the potential to enhance energy density and lower battery cathode costs. However, their widespread adoption faces obstacles like substantial voltage hysteresis and poor stability. The current research addresses these challenges by achieving a non-hysteresis, long-term stable oxygen redox reaction in the P3-type Na2/3Cu1/3Mn2/3O2. Here we show this is accomplished by forming spin singlet states during charge and discharge. Detailed analysis, including in-situ X-ray diffraction, shows highly reversible structural changes during cycling. In addition, local CuO6 Jahn-Teller distortions persist throughout, with dynamic Cu-O bond length variations. In-situ hard X-ray absorption and ex-situ soft X-ray absorption study, along with density function theory calculations, reveal two distinct charge compensation mechanisms at approximately 3.66 V and 3.99 V plateaus. Notably, we observe a Zhang-Rice-like singlet state during 3.99 V charging, offering an alternative charge compensation mechanism to stabilize the active oxygen redox reaction. Oxygen redox in transition metal oxides enhances the energy content of Na-ion batteries but is typically plagued by poor reversibility. Here, the authors achieve non-hysteresis through the formation of a spin singlet state to stabilize the active oxygen redox reaction in P3-type Na2/3Cu1/3Mn2/3O2. [ABSTRACT FROM AUTHOR]

Purpose: Pancreatic adenocarcinoma (PAAD) remains a highly aggressive gastrointestinal malignancy with a dismal prognosis. Pyroptosis has a key role in tumor development. Long noncoding RNAs (lncRNAs) are involved in tumorigenesis and pyroptosis regulation. However, the prognostic potential and function of pyroptosis-related lncRNAs (PRLs) in PAAD remain unclear. We aimed to identify PRLs with promising predictive value for PAAD prognosis and investigate the mechanism by which PRLs affect pyroptosis and PAAD development. Methods: Key genes that regulate pyroptosis were determined from previous studies, and PRLs were identified from lncRNAs shown to be co-expressed in The Cancer Genome Atlas. Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model was used to establish a prognostic PRL signature. The clinical significance and functional mechanisms of LINC01133 were explored in vitro and in vivo. Results: A seven-lncRNA signature was established and the high-risk subgroup exhibited a shorter survival time. With lower immune infiltration abundance, poor immune function, and higher tumor mutational burden (TMB), the high-risk subgroup reflected a more immunosuppressive status with a greater scope for benefiting from immunotherapy. After LINC01133 knockdown, PAAD cells showed lower viability and higher pyroptosis-related gene expression. LINC01133 functioned as a competing endogenous RNA to sequester miR-30b-5p from sponging SIRT1 mRNA to inhibit PAAD pyroptosis. Conclusion: With significant prognostic value, our PRL signature are involved in the biological processes of PAAD cells and associated with the immune environment. LINC01133 suppresses pyroptosis to promote PAAD development and could serve as a potential target for PAAD treatment. [ABSTRACT FROM AUTHOR]

Over the past decades, the primary interest in vaccine efficacy or immunogenicity evaluation mostly focuses on the biological effect of immunization in complying with the vaccination schedule in a targeted population. The safety questions, which are essential for vaccines as they are generally given to large healthy populations, need to be clearly defined to reflect the risk assessment of interest. ICH E9 (R1) provides a structured framework to clarify the clinical questions and formulate the treatment effect as an estimand. This paper applies the estimand framework to vaccine clinical trials on common clinical questions regarding efficacy, immunogenicity, and safety. [ABSTRACT FROM AUTHOR]

Defining the right question of interest is important to a clinical study. ICH E9 (R1) introduces the framework of an estimand and its five attributes, which provide a basis for connecting different components of a study with its clinical questions. Most of the applications of the estimand framework focus on efficacy instead of safety assessment. In this paper, we expand the estimand framework into the safety evaluation and compare/contrast the similarity and differences between safety and efficacy estimand. Furthermore, we present and discuss applications of a safety estimand to oncology trials and pooled data analyses. At last, we also discuss the potential usage of safety estimand to handle the impacts of COVID-19 pandemic on safety assessment. [ABSTRACT FROM AUTHOR]

Purpose: Growth hormone-secreting pituitary adenoma (GHPA) is an insidious disease with persistent hypersecretion of growth hormone and insulin-like growth factor 1, causing increased morbidity and mortality. Previous studies have investigated the transcription of GHPA. However, the gene regulatory landscape has not been fully characterized. The objective of our study was to unravel the changes in chromatin accessibility and transcription in GHPA. Methods: Six patients diagnosed with GHPA in the Department of Neurosurgery at Huashan Hospital were enrolled in our study. Primary pituitary adenoma tissues and adjacent normal pituitary specimens with no morphologic abnormalities from these six patients were obtained at surgery. RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) were applied to investigate the underlying relationship between gene expression and chromatin accessibility changes in GHPA. Results: Totally, 1528 differential expression genes (DEGs) were identified by transcriptomics analyses, including 725 up-regulated and 803 down-regulated. Further, we obtained 64 significantly DEGs including 10 DEGs were elevated and 54 DEGs were negligibly expressed in tumors tissues. The up-regulated DEGs were mainly involved in terms related to synapse formation, nervous system development and secretory pathway. In parallel, 3916 increased and 2895 decreased chromatin-accessible regions were mapped by ATAC-seq. Additionally, the chromatin accessible changes were frequently located adjacent to transcription factor CTCF and Rfx2 binding site. Conclusions: Our results are the first to demonstrate the landscape of chromatin accessibility in GHPA, which may contribute to illustrate the underlying transcriptional regulation mechanism of this disease. [ABSTRACT FROM AUTHOR]

Conversion of CO2 to useful fuels and chemicals has gained great attention in the past decades; yet the challenge persists due to the inert nature of CO2 and the wide range of products formed. Pd-based catalysts are extensively studied to facilitate CO2 hydrogenation to methanol via a reverse water gas shift (rWGS) pathway or formate pathway where formic acid may serve as an intermediate species. Here, we report the selective production of formic acid on the stable Pd(111) surface phase under CO2 hydrogenation conditions, which is fully covered by chemisorbed hydrogen, using combined Density Functional Theory (DFT) and Kinetic Monte Carlo (KMC) simulations. The results show that with the full coverage of hydrogen, instead of producing methanol as reported for Pd(111), the CO2 activation is highly selective to formic acid via a multi-step process involving the carboxyl intermediate. The high formic acid selectivity is associated with surface hydrogen species on Pd(111), which not only acts as a hydrogen reservoir to facilitate the hydrogenation steps, but also enables the formation of confined vacancy sites to facilitate the production and removal of formic acid. Our study highlights the importance of reactive environments, which can transform the surface structures and thus tune the activity/selectivity of catalysts. [ABSTRACT FROM AUTHOR]

Background: Tumor cells exhibited phenotypic and molecular characteristics similar to their lineage progenitor cells. Liver developmental signaling pathways are showed to be associated with HCC development and oncogenesis. The similarities of expression profiling between liver progenitors (LPs) and HCC suggest that understanding the molecular mechanism during liver development could provide insights into HCC. Methods: To profile the dynamic gene expression during liver development, cells from an in vitro liver differentiation model and two paired hepatocellular carcinoma (HCC) samples were analyzed using deep RNA sequencing. The expression levels of selected genes were analyzed by qRT-PCR. Moreover, the role of a key transcription factor, pituitary homeobox 2 (PITX2), was characterized via in vitro and vivo functional assays. Furthermore, molecular mechanism studies were performed to unveil how PITX2C regulate the key developmental factors in LPs, thereby increasing the stemness of HCC. Results: PITX2 was found to exhibit a similar expression pattern to specific markers of LPs. PITX2 consists of three isoforms (PITX2A/B/C). The expression of PITX2 is associated with tumor size and overall survival rate, whereas only PITX2C expression is associated with AFP and differentiation in clinical patients. PITX2A/B/C has distinct functions in HCC tumorigenicity. PITX2C promotes HCC metastasis, self-renewal and chemoresistance. Molecular mechanism studies showed that PITX2C could up-regulate RALYL which could enhance HCC stemness via the TGF-β pathway. Furthermore, ChIP assays confirmed the role of PITX2C in regulating key developmental factors in LP. Conclusion: PITX2C is a newly discovered transcription factor involved in hepatic differentiation and could increase HCC stemness by upregulating key transcriptional factors related to liver development. [ABSTRACT FROM AUTHOR]

Cell plasticity endows differentiated cells with competence to be reprogrammed to other lineages. Although extrinsic factors driving cell-identity conversion have been extensively characterized, it remains elusive which intrinsic epigenetic attributes, including high-order chromatin organization, delineate cell plasticity. By analysing the transcription-factor-induced transdifferentiation from fibroblasts to hepatocytes, we uncovered contiguous compartment-switchable regions (CSRs) as a unique chromatin unit. Specifically, compartment B-to-A CSRs, enriched with hepatic genes, possessed a mosaic status of inactive chromatin and pre-existing and continuous accessibility in fibroblasts. Pre-existing accessibility enhanced the binding of inducible factor Foxa3, which triggered epigenetic activation and chromatin interaction as well as hepatic gene expression. Notably, these changes were restrained within B-to-A CSR boundaries that were defined by CTCF occupancy. Moreover, such chromatin organization and mosaic status were detectable in different cell types and involved in multiple reprogramming processes, suggesting an intrinsic chromatin attribute in understanding cell plasticity. [ABSTRACT FROM AUTHOR]

Education has been proved to be one of the most important variables influencing intergenerational income mobility. Existing literature decomposes the indirect effect of education on intergenerational income mobility into two components: the effect of the correlation between a parents' income and their children's education, and the effect of the return to education. Basing on the framework of existed studies, this paper explores a beneficial application to measure the two components, and checks which effect is more important in explaining the inter‐generational income mobility in Chinese society. Using data from the China Health and Nutrition Survey (CHNS), the research analyzes how education affects inter‐generational income mobility, and estimates the respective contributions of the two effects of education. The empirical results show that the effect of education is of importance in explaining the increase in the intergenerational income correlation for 1960s, 1970s and 1980s of Chinese age groups. Meanwhile, after decomposing the effect of education, we find that the return on education has stronger explanatory power on intergenerational income mobility than the correlation between a father's income and his child's education. Therefore, the return to education should be the center of policy design for the Chinese government. [ABSTRACT FROM AUTHOR]

The aging of population has resulted in a significant increase in the prevalence of rheumatoid arthritis (RA), which is a persistent and recurrent synovial inflammation caused by abnormal immune activation. Herein, the authors designed an inflammation‐triggered disassembly (ITD) nanoplatform by a supramolecular assembly method, which controls the decomposition and drug release through changes in cytokine concentrations and redox potentials during the onset of arthritis, and its dual‐targeted synergistic effect on collagen‐induced arthritis (CIA) rats resulted in higher cell death rate and immunosuppressive rate. Meanwhile, they propose the local dynamic dependent imaging (LDDI) technology to diagnose the disease status, which may produce corresponding changes with the fluctuation of inflammatory activity and improve the accuracy of dual‐target therapy by monitoring the synovial changes through in situ photoactivation of the second near infrared light (NIR‐II). Very importantly, histological analysis shows that ITD strategy relieved joint destruction and cartilage degeneration and its clinical score is similar to that of the healthy group. Their work provides an effective strategy for the early diagnosis and treatment of acute and chronic inflammation diseases, which can interfere to abnormal immune activation, rather than affecting the normal function of immune system. [ABSTRACT FROM AUTHOR]

Background: Tumour‐associated macrophages (TAMs) play an important role in promoting the progression of pancreatic ductal adenocarcinoma (PDAC). Here, we aimed to study the epigenetic mechanisms in regulating pro‐tumour M2‐polarised TAMs in the PDAC tumour microenvironment. Methods: This study was conducted based on ex vivo TAMs isolated from PDAC tissues and in vitro THP1‐derived TAM model. RNA‐sequencing (RNA‐seq), assay for transposase‐accessible chromatin with sequencing and chromatin immunoprecipitation sequencing were performed to investigate gene expression, chromatin accessibility, transcription factor binding sites and histone modifications. Gene knockdown in THP1‐derived TAMs was performed with lentivirus, and the impact of THP1‐derived TAMs on invasion and metastasis ability of PDAC cells were investigated with in vitro and in vivo functional assays. RNA‐chromatin interaction was analysed by chromatin isolation through RNA purification with sequencing. RNA‐protein interaction was studied by RNA immunoprecipitation and RNA pull‐down. Results: Our data showed that the transcription factor CTCF (CCCTC‐binding factor) was highly expressed in TAMs and predicted to be significantly enriched in hyper‐accessible chromatin regions when compared to monocytes. High infiltration of CTCF+ TAMs was significantly associated with poor prognosis in PDAC patients. Knockdown of CTCF in THP1‐derived TAMs led to the down‐regulation of specific markers for M2‐polarised TAMs, including CD206 and CD163. When THP1‐derived TAMs with CTCF knockdown, they showed a decreased ability of invasion and metastasis. Further integrative analysis of multi‐omics data revealed that prostaglandin‐endoperoxide synthase 2 (PTGS2) and PTGS2 antisense NF‐κB1 complex‐mediated expression regulator RNA (PACERR) were critical downstream targets of CTCF and positively correlated with each other, which are closely situated on a chromosome. Knockdown of PACERR exhibited a similar phenotype as observed in CTCF knockdown THP1‐derived TAMs. Moreover, PACERR could directly bind to CTCF and recruit histone acetyltransferase E1A binding protein p300 to the promoter regions of PACERR and PTGS2, thereby enhancing histone acetylation and gene transcription, promoting the M2 polarization of TAMs in PDAC. Conclusions: Our study demonstrated a novel epigenetic regulation mechanism of promoting pro‐tumour M2‐polarised TAMs in the PDAC tumour microenvironment. [ABSTRACT FROM AUTHOR]

Background: DNA methylation alteration is frequently observed in Lung adenocarcinoma (LUAD) and may play important roles in carcinogenesis, diagnosis, and prognosis. Thus, this study aimed to construct a reliable methylation-based nomogram, guiding prognostic classification screening and personalized medicine for LUAD patients.Method: The DNA methylation data, gene expression data and corresponding clinical information of lung adenocarcinoma samples were extracted from The Cancer Genome Atlas (TCGA) database. Differentially methylated sites (DMSs) and differentially expressed genes (DEGs) were obtained and then calculated correlation by pearson correlation coefficient. Functional enrichment analysis and Protein-protein interaction network were used to explore the biological roles of aberrant methylation genes. A prognostic risk score model was constructed using univariate Cox and LASSO analysis and was assessed in an independent cohort. A methylation-based nomogram that included the risk score and the clinical risk factors was developed, which was evaluated by concordance index and calibration curves.Result: We identified a total of 1362 DMSs corresponding to 471 DEGs with significant negative correlation, including 752 hypermethylation sites and 610 hypomethylation sites. Univariate cox regression analysis showed that 59 DMSs were significantly associated with overall survival. Using LASSO method, we constructed a three-DMSs signature that was independent predictive of prognosis in the training cohort. Patients in high-risk group had a significant shorter overall survival than patients in low-risk group classified by three-DMSs signature (log-rank p = 1.9E-04). Multivariate cox regression analysis proved that the three-DMSs signature was an independent prognostic factor for LUAD in TCGA-LUAD cohort (HR = 2.29, 95%CI: 1.47-3.57, P = 2.36E-04) and GSE56044 cohort (HR = 2.16, 95%CI: 1.19-3.91, P = 0.011). Furthermore, a nomogram, combining the risk score with clinical risk factors, was developed with C-indexes of 0.71 and 0.70 in TCGA-LUAD and GSE56044 respectively.Conclusions: The present study established a robust three-DMSs signature for the prediction of overall survival and further developed a nomogram that could be a clinically available guide for personalized treatment of LUAD patients. [ABSTRACT FROM AUTHOR]

Following the fundamental research conducted by J. B. Goodenough, the important role of electron localization induced by elemental substitution is studied. The size and electron negativity of host and substituting ions are two important factors in tuning material properties such as local structure and transition metal (TM) oxygen covalency. However, another factor, electron localization, which is widely studied in catalyst research but largely overlooked for battery materials, deserves systematic studies. A combined investigation using synchrotronbased X‐ray spectroscopy and theoretical calculations is carried out on the Li‐Co‐Mn‐O model system in which the substituting cation Mn4+, with its 3d3 electronic structure, is used as a promoter for electron localization. Results indicate that electron localization greatly influences the CoO bond by making it less covalent, which increases the delithiation voltage. It is also found that during charge/discharge, electron localization tends to make TM K‐edge X‐ray absorption near edge spectroscopy (XANES) spectra show a more "rigid shift" behavior while electron delocalization makes the XANES exhibit a "shape change." It clearly explains why the K‐edge XANES data of some TM oxides show no "rigid shift" while the nominal valence states changed. This work highlights the importance of electron localization with guidance for XANES interpretation. [ABSTRACT FROM AUTHOR]

Lithium-rich nickel-manganese-cobalt (LirNMC) layered material is a promising cathode for lithium-ion batteries thanks to its large energy density enabled by coexisting cation and anion redox activities. It however suffers from a voltage decay upon cycling, urging for an in-depth understanding of the particle-level structure and chemical complexity. In this work, we investigate the Li1.2Ni0.13Mn0.54Co0.13O2 particles morphologically, compositionally, and chemically in three-dimensions. While the composition is generally uniform throughout the particle, the charging induces a strong depth dependency in transition metal valence. Such a valence stratification phenomenon is attributed to the nature of oxygen redox which is very likely mostly associated with Mn. The depth-dependent chemistry could be modulated by the particles' core-multi-shell morphology, suggesting a structural-chemical interplay. These findings highlight the possibility of introducing a chemical gradient to address the oxygen-loss-induced voltage fade in LirNMC layered materials. Lithium-rich layered material deserves in-depth understanding because it has large capacity enabled by both cation and anion activities. Here, authors apply 3D spectro-tomography with nano resolution to reveal the multi-layer morphology and depth-dependent transition metal valence distribution associated with oxygen redox. [ABSTRACT FROM AUTHOR]

A method is proposed that uses the metal casing of an oil and gas production well to construct a long dipole emission line source and applies pseudorandom multifrequency excitation signals to it to identify reservoir characteristics of interwell reservoirs. This method can significantly improve the work efficiency and precision of electrical prospecting. The cross‐well pseudorandom response signal contains multiple main frequency components, as well as various measuring frequency points. Targeting the frequency components with different amplitudes and initial phases in the pseudorandom signal, the digital coherent detection method and its noise resistance are studied. Using this method can effectively extract the amplitude and phase information of each frequency component in different noise environments and has a strong ability to suppress signals of other frequencies. In the heterogeneous interwell reservoir detection model, the amplitude characteristics of each frequency component of the pseudorandom electromagnetic response at the measuring line with different well spacings are extracted. Numerical results show that the curve of equal‐frequency measurement appears downwardly "concave" at the interface of the low‐resistivity interlayer, and upwardly "convex" at the interface of the high‐resistivity interlayer. With the increase in the resistivity of the low‐resistivity interlayer, the dynamic range of the extraction component of the same frequency decreases gradually, and the family of equal‐frequency response curves overlap with each other. By contrast, for the high‐resistivity interlayer, as its resistivity gradually increases, the dynamic range of the extraction component of same frequency also increases gradually. Moreover, as well spacing varies, the response characteristics of the equal‐frequency curve family on different measuring lines are also obviously different. The digital coherent detection method significantly simplifies the receiving circuit system. In practical application, response information of different discrete frequency components can be extracted according to requirements. This thus provides a theoretical basis for the extraction of resistivity and characteristic identification of interwell heterogeneous oil and gas reservoirs. [ABSTRACT FROM AUTHOR]

Pancreatic cancer remains a lethal type of cancer with poor prognosis. Molecular classification enables in-depth, precise prognostic assessment. This study is aimed at identifying a robust and simple mRNA signature to predict the overall survival (OS) of pancreatic cancer (PC) patients. Differentially expressed genes (DEGs) between 45 paired pancreatic tumor samples and adjacent healthy tissues were selected. For risk determination, a LASSO Cox regression model with DEGs was used to generate the OS-associated risk score formula for the training cohort containing 177 PC patients. Another five independent datasets were used as the testing cohort to determine the predictive efficiency for further validation. In total, 441 DEGs were selected after considering the enrichment of classical pathways, such as EMT, cell cycle, cell adhesion, and PI3K-AKT. A five-gene signature for risk discrimination was established with high efficacy using LASSO Cox regression in the training group. External validation showed that patients identified by the gene expression signature to be in the high-risk group had poorer prognosis compared with the low-risk patients. Further investigation identified the differential epigenetic modification patterns of the five genes, which indicated their roles in tumor progression and their effect on therapy. In conclusion, we constructed a robust five-gene expression signature that could predict the OS of PC patients, offering a new insight for risk discrimination in daily clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: The Li‐rich layer‐structured oxides are regarded one of the most promising candidates of cathode materials for high energy‐density Li‐ion batteries. However, the uninterrupted migration of the transition metal (TM) ions during cycling and the resultant continuous fading of their discharge potentials bring challenges to the battery design and impede their commercial applications. Various efforts have been taken to suppress the migration of the TM ions such as surface modification and elemental substitution, but no success has been achieved to date. Another strategy hereby is proposed to address these issues, in which the TM migration is promoted and the layered material is transformed to a rocksalt in the first few charge/discharge cycles by specially designing a novel Li‐rich layer‐structured Li1.2Mo0.6Fe0.2O2 on the basis of density functional theory calculations. With such, the continuous falling of the discharge potential is detoured due to enhanced completion of the cation mixing. In‐depth studies such as aberration‐corrected scanning transmission electron microscopy confirm the drastic structural change at the atomic scale, and in situ X‐ray absorption spectroscopy and Mössbauer spectroscopy clarify its charge compensation mechanism. This new strategy provides revelation for the development of the Li‐rich layered oxides with mitigated potential decay and a longer lifespan. [ABSTRACT FROM AUTHOR]

Solid state electrolytes with high Li ion conduction are vital to the development of all-solid-state lithium batteries. Lithium thiophosphate Li3PS4 is the parent material of a series of Li superionic conductors Li10MX2S12 (M = Ge, Sn,…; X = P, Si,…), and β-Li3PS4 shows relatively high ionic conductivity itself, though it is not room-temperature stable. The positive effects of introducing O dopants into β-Li3PS4 to stabilize the crystal phase and improve the ionic conducting behaviour are revealed in this study. With the aid of first-principles density functional theory (DFT) computations and quasi-empirical bond-valence calculations, the effects of O doping at different concentrations on the properties of β-Li3PS4 is thoroughly investigated from the aspects of lattice structures, electronic structures, ionic transport properties, the interface stability against Li and the thermodynamic stability. An oxygen-driven transition from two-dimensional to three-dimensional transport behaviour is found and the oxygen dopants play the role as a connector of 2D paths. Based on all these simulation results, hopefully our research can provide a new strategy for the modification of lithium thiophosphate solid electrolytes. [ABSTRACT FROM AUTHOR]

There has been growing interest in applying tissue engineering to stem cell-based regeneration therapies. We have previously reported that zebrafish can faithfully regenerate complicated tissue structures through blastemal cell type conversions and tissue reorganization. To unveil the regenerative factors and engineering arts of blastemal regeneration, we conducted transcriptomal analyses at four time points corresponding to preamputation, re-epitheliation, blastemal formation, and respecification. By combining the hierarchical gene ontology term network, the DAVID annotation system, and Euclidean distance clustering, we identified four signaling pathways: foxi1-foxo1b-pou3f1, pax3a-mant3a-col11/col2, pou5f1-cdx4-kdrl, and isl1-wnt11 PCP-sox9a. Results from immunohistochemical staining and promoter-driven transgenic fish suggest that these pathways, respectively, define wound epidermis reconstitution, cell type conversions, blastemal angiogenesis/vasculogenesis, and cartilage matrix-orientation. Foxi1 morpholino-knockdown caused expansions of Foxo1b- and Pax3a-expression in the basal layer-blastemal junction region. Moreover, foxi1 morphants displayed increased sox9a and hoxa2b transcripts in the embryonic pharyngeal arches. Thus, a Foxi1 signal switch is required to establish correct tissue patterns, including re-epitheliation and blastema formation. This study provides novel insight into a blastema regeneration strategy devised by epithelial cell transdifferentiation, blood vessel engineering, and cartilage matrix deposition. S tem C ells 2015;33:806-818 [ABSTRACT FROM AUTHOR]

Background: Tumor cells exhibited phenotypic and molecular characteristics similar to their lineage progenitor cells. Liver developmental signaling pathways are showed to be associated with HCC development and oncogenesis. The similarities of expression profiling between liver progenitors (LPs) and HCC suggest that understanding the molecular mechanism during liver development could provide insights into HCC. Methods: To profile the dynamic gene expression during liver development, cells from an in vitro liver differentiation model and two paired hepatocellular carcinoma (HCC) samples were analyzed using deep RNA sequencing. The expression levels of selected genes were analyzed by qRT-PCR. Moreover, the role of a key transcription factor, pituitary homeobox 2 (PITX2), was characterized via in vitro and vivo functional assays. Furthermore, molecular mechanism studies were performed to unveil how PITX2C regulate the key developmental factors in LPs, thereby increasing the stemness of HCC. Results: PITX2 was found to exhibit a similar expression pattern to specific markers of LPs. PITX2 consists of three isoforms (PITX2A/B/C). The expression of PITX2 is associated with tumor size and overall survival rate, whereas only PITX2C expression is associated with AFP and differentiation in clinical patients. PITX2A/B/C has distinct functions in HCC tumorigenicity. PITX2C promotes HCC metastasis, self-renewal and chemoresistance. Molecular mechanism studies showed that PITX2C could up-regulate RALYL which could enhance HCC stemness via the TGF-β pathway. Furthermore, ChIP assays confirmed the role of PITX2C in regulating key developmental factors in LP. Conclusion: PITX2C is a newly discovered transcription factor involved in hepatic differentiation and could increase HCC stemness by upregulating key transcriptional factors related to liver development. [ABSTRACT FROM AUTHOR]

The Sonic hedgehog (Shh) signaling pathway is crucial for pattern formation in early central nervous system development. By systematically analyzing high-throughput in situ hybridization data of E11.5 mouse brain, we found that Shh and its receptor Ptch1 define two adjacent mutually exclusive gene expression domains: Shh+Ptch1− and Shh−Ptch1+. These two domains are associated respectively with Foxa2 and Gata3, two transcription factors that play key roles in specifying them. Gata3 ChIP-seq experiments and RNA-seq assays on Gata3-knockdown cells revealed that Gata3 up-regulates the genes that are enriched in the Shh−Ptch1+ domain. Important Gata3 targets include Slit2 and Slit3, which are involved in the process of axon guidance, as well as Slc18a1, Th and Qdpr, which are associated with neurotransmitter synthesis and release. By contrast, Foxa2 both up-regulates the genes expressed in the Shh+Ptch1− domain and down-regulates the genes characteristic of the Shh−Ptch1+ domain. From these and other data, we were able to reconstruct a gene regulatory network governing both domains. Our work provides the first genome-wide characterization of the gene regulatory network involved in the Shh pathway that underlies pattern formation in the early mouse brain. [ABSTRACT FROM AUTHOR]

Autophagy was found to play an antimicrobial or antiparasitic role in the activation of host cells to defend against intracellular pathogens, at the same time, pathogens could compete with host cell and take advantage of autophagy to provide access for its proliferation, but there are few articles for studying the outcome of this competition between host cell and pathogens. Therefore, the aim of our study was to investigate the relationship between autophagy activated by Toxoplasma gondii (T. gondii) and proliferation of T. gondii affected by autophagy in vitro. Firstly, human embryonic fibroblasts (HEF) cells were infected with T. gondii for different times. The monodansylcadaverine (MDC) staining, acridine orange (AO) staining, punctuate GFP-LC3 distribution, and transmission electron microscopy (TEM) assays were conducted, and the results were consistent in showing that gondii infection could induce autophagy. Secondly, HEF cells were infected with T. gondii and treated with autophagy inhibitor bafilomycin A1 or inducer lithium chloride for different times. Giemsa staining was conducted, and the results exhibited that T. gondii infection-induced autophagy could in turn promote T. gondii proliferation. Simultaneously, the results of Giemsa staining also revealed that autophagy inhibitor could reduce the number of each cell infected with T. gondii and inhibit T. gondii proliferation. In contrast, autophagy inducer could increase the number of each cell infected with T. gondii and encourage T. gondii proliferation. Therefore, our study suggests that T. gondii infection could activate autophagy, and this autophagy could in turn facilitate T. gondii proliferation in HEF cells for limiting nutrients. [ABSTRACT FROM AUTHOR]

Toxoplasma gondii is an apicomplexan parasite capable of transplacental transmission to cause spontaneous abortion or significant disease in the surviving neonate. Different from the dominant genotypes of T. gondii strains in European and North American which belong to three distinct clonal lineages, type I, type II, and type III, isolates from China possess the predominant genotype of China 1(ToxoDB#9) with a different virulence. The genotype-associated pathogenesis has been investigated previously. Based on two isolates of T. gondii from Chinese wild cats, a murine model of pregnancy and one transwell system in vitro, here we reported differentially polarized activation of macrophages induced by genotype China 1 strains, TgCtwh3 and TgCtwh6 with different virulence to mice, and its impact on trophoblast apoptosis. The results showed that macrophages were alternatively activated when infected with virulent TgCtwh3 while classically activated when infected with low virulent (cyst-forming) TgCtwh6 both in vitro and in vivo. By the analysis of flow cytometry, the percentage of the Th1 cells in two infection groups decreased significantly, and the Th2 cells from spleen escalated only in the virulent TgCtwh3 group. Interestingly, the high parasite burden was noted in the placenta of TgCtwh3-infected group whereas the inflammatory cells infiltration predominates in the TgCtwh6-infected group. In vivo trophoblast apoptosis in TgCtwh3 group was found to be more obvious when compared with TgCtwh6 although it was present in both. The present observations indicate that polarization of macrophages and modulation of Th subsets induced by the isolates with identical genotype but different virulence could contribute to trophoblast apoptosis through different mechanisms, suggesting a virulence-associated pathogenesis of T. gondii in abnormal pregnant outcome. [ABSTRACT FROM AUTHOR]

This paper explores the influence of land holding on rural-urban migration using China's 2008 household survey data. It shows that the contradictory findings of existing published literature can be explained by introducing a migration distance variable. The empirical studies show that land holding plays a different role in short-distance and long-distance migration. Land holding has a U-shaped curve association with the probability of short-distance migration and has an inverted-U-shaped association with the probability of long-distance migration. Therefore, the government needs to provide more job information and migration subsidies to farmers who have little land to overcome difficulties in the process of migration so as to reduce rural-urban inequality. [ABSTRACT FROM AUTHOR]

Li-Ti Cation Mixing Enhanced Structural and Performance Stability of Li-Rich Layered Oxide The affiliation information for the National Synchrotron Radiation Research Center was presented incorrectly. The authors apologize for any inconvenience caused. [Extracted from the article]

Li‐rich layered metal oxides are one type of the most promising cathode materials in lithium‐ion batteries but suffer from severe voltage decay during cycling because of the continuous transition metal (TM) migration into the Li layers. A Li‐rich layered metal oxide Li1.2Ti0.26Ni0.18Co0.18Mn0.18O2 (LTR) is hereby designed, in which some of the Ti4+ cations are intrinsically present in the Li layers. The native Li–Ti cation mixing structure enhances the tolerance for structural distortion and inhibits the migration of the TM ions in the TMO2 slabs during (de)lithiation. Consequently, LTR exhibits a remarkable cycling stability of 97% capacity retention after 182 cycles, and the average discharge potential drops only 90 mV in 100 cycles. In‐depth studies by electron energy loss spectroscopy and aberration‐corrected scanning transmission electron microscopy demonstrate the Li–Ti mixing structure. The charge compensation mechanism is uncovered with X‐ray absorption spectroscopy and explained with the density function theory calculations. These results show the superiority of introducing transition metal ions into the Li layers in reinforcing the structural stability of the Li‐rich layered metal oxides. These findings shed light on a possible path to the development of Li‐rich materials with better potential retention and a longer lifespan. [ABSTRACT FROM AUTHOR]

Nickel‐rich layered materials LiNi1‐x‐yMnxCoyO2 are promising candidates for high‐energy‐density lithium‐ion battery cathodes. Unfortunately, they suffer from capacity fading upon cycling, especially with high‐voltage charging. It is critical to have a mechanistic understanding of such fade. Herein, synchrotron‐based techniques (including scattering, spectroscopy, and microcopy) and finite element analysis are utilized to understand the LiNi0.6Mn0.2Co0.2O2 material from structural, chemical, morphological, and mechanical points of view. The lattice structural changes are shown to be relatively reversible during cycling, even when 4.9 V charging is applied. However, local disorder and strain are induced by high‐voltage charging. Nano‐resolution 3D transmission X‐ray microscopy data analyzed by machine learning methodology reveal that high‐voltage charging induced significant oxidation state inhomogeneities in the cycled particles. Regions at the surface have a rock salt–type structure with lower oxidation state and build up the impedance, while regions with higher oxidization state are scattered in the bulk and are likely deactivated during cycling. In addition, the development of micro‐cracks is highly dependent on the pristine state morphology and cycling conditions. Hollow particles seem to be more robust against stress‐induced cracks than the solid ones, suggesting that morphology engineering can be effective in mitigating the crack problem in these materials. [ABSTRACT FROM AUTHOR]

Using a pseudo-random sequence to encode the transmitted waveform can significantly improve the working efficiency and depth of detection of electromagnetic exploration. The selection of parameters of pseudo-random sequence plays an important role in correlation identification and noise suppression. A discrete cycle correlation identification method for extracting the earth impulse response is proposed. It can suppress the distortion in the early stage of the excitation field and the glitches of the cross correlation function by traditional method. This effectively improves the accuracy of correlation identification. The influence of the order and the cycles of m-series pseudo-random coding on its autocorrelation properties is studied. The numerical results show that, with the increase of the order of m-sequence, the maximum out-of-phase periodic autocorrelation function decreases rapidly. Therefore, it is very beneficial to achieve synchronization. The limited-cycle m-sequences have good autocorrelation properties. As the period of the m-sequence increases and the width of the symbol decreases, the overall autocorrelation becomes closer to the impact function. The discussion of the influence of symbol width and period of m-sequence on its frequency bandwidth and power spectral density shows that the narrower the symbol width, the wider its occupied band. The longer the period, the smaller the power spectral line spacing. The abilities of m-sequence to suppress DC (Direct-current) interference, Schumann frequency noise, and sine-wave noise are analyzed. Numerical results show that the m-sequence has excellent ability to suppress DC interference and Schumann frequency noise. However, for high-order harmonic noise, the correlation identification error appears severe oscillation in the middle and late stages of the impulse response. It indicates that the ability of m-sequence to suppress high-frequency sinusoidal noise is deteriorated. In practical applications, the parameters of the transmitted waveform should be reasonably selected in combination with factors including transmitter performance, hardware noise, and ambient noise level to achieve the best identification effect. [ABSTRACT FROM AUTHOR]

The Redhead cichlid (Vieja synspila) is an important aquarium fish and a useful phylogenetic organism of the Cichlidae family. In this study, we sequenced the mitochondrial genome of the Redhead cichlid for the first time. The mitogenome (16,543 bp) had the typical mitochondrial characteristics of other cichlid fish, including 13 protein-coding, 22 tRNA, two rRNA genes and one putative control region. This sequence will be helpful in studying the phylogenetic relationships between cichlid fish. [ABSTRACT FROM AUTHOR]