Integration of clinical phenoms and metabolomics facilitates precision medicine for lung cancer.

Lung cancer is a common malignancy that is frequently associated with systemic metabolic disorders. Early detection is pivotal to survival improvement. Although blood biomarkers have been used in its early diagnosis, missed diagnosis and misdiagnosis still exist due to the heterogeneity of lung cancer. Integration of multiple biomarkers or trans-omics results can improve the accuracy and reliability for lung cancer diagnosis. As metabolic reprogramming is a hallmark of lung cancer, metabolites, specifically lipids might be useful for lung cancer detection, yet systematic characterizations of metabolites in lung cancer are still incipient. The present study profiled the polar metabolome and lipidome in the plasma of lung cancer patients to construct an inclusive metabolomic atlas of lung cancer. A comprehensive analysis of lung cancer was also conducted combining metabolomics with clinical phenotypes. Furthermore, the differences in plasma lipid metabolites were compared and analyzed among different lung cancer subtypes. Alcohols, amides, and peptide metabolites were significantly increased in lung cancer, while carboxylic acids, hydrocarbons, and fatty acids were remarkably decreased. Lipid profiling revealed a significant increase in plasma levels of CER, PE, SM, and TAG in individuals with lung cancer as compared to those in healthy controls. Correlation analysis confirmed the association between a panel of metabolites and TAGs. Clinical trans-omics studies elucidated the complex correlations between lipidomic data and clinical phenotypes. The present study emphasized the clinical importance of lipidomics in lung cancer, which involves the correlation between metabolites and the expressions of other omics, ultimately influencing clinical phenotypes. This novel trans-omics network approach would facilitate the development of precision therapy for lung cancer.

Playing Extensive Games with Learning of Opponent's Cognition.

Decision-making is a basic component of agents' (e.g., intelligent sensors) behaviors, in which one's cognition plays a crucial role in the process and outcome. Extensive games, a class of interactive decision-making scenarios, have been studied in diverse fields. Recently, a model of extensive games was proposed in which agent cognition of the structure of the underlying game and the quality of the game situations are encoded by artificial neural networks. This model refines the classic model of extensive games, and the corresponding equilibrium concept-cognitive perfect equilibrium (CPE)-differs from the classic subgame perfect equilibrium, since CPE takes agent cognition into consideration. However, this model neglects the consideration that game-playing processes are greatly affected by agents' cognition of their opponents. To this end, in this work, we go one step further by proposing a framework in which agents' cognition of their opponents is incorporated. A method is presented for evaluating opponents' cognition about the game being played, and thus, an algorithm designed for playing such games is analyzed. The resulting equilibrium concept is defined as adversarial cognition equilibrium (ACE). By means of a running example, we demonstrate that the ACE is more realistic than the CPE, since it involves learning about opponents' cognition. Further results are presented regarding the computational complexity, soundness, and completeness of the game-solving algorithm and the existence of the equilibrium solution. This model suggests the possibility of enhancing an agent's strategic ability by evaluating opponents' cognition.

CRMSNet: A deep learning model that uses convolution and residual multi-head self-attention block to predict RBPs for RNA sequence.

RNA-binding proteins (RBPs) play significant roles in many biological life activities, many algorithms and tools are proposed to predict RBPs for researching biological mechanisms of RNA-protein binding sites. Deep learning algorithms based on traditional machine learning get better result for predicting RBPs. Recently, deep learning method fused with attention mechanism has attracted huge attention in many fields and gets competitive result. Thus, attention mechanism module may also improve model performance for predicting RNA-protein binding sites. In this study, we propose convolutional residual multi-head self-attention network (CRMSNet) that combines convolutional neural network (CNN), ResNet, and multi-head self-attention blocks to find RBPs for RNA sequence. First, CRMSNet incorporates convolutional neural networks, recurrent neural networks, and multi-head self-attention block. Second, CRMSNet can draw binding motif pictures from the convolutional layer parameters. Third, attention mechanism module combines the local and global RNA sequence information for capturing long sequence feature. CRMSNet gets competitive AUC (area under the receiver operating characteristic [ROC] curve) result in a large-scale dataset RBP-24. And CRMSNet experiment result is also compared with other state-of-the-art methods. The source code of our proposed CRMSNet method can be found in https://github.com/biomg/CRMSNet.

Analysis of factors influencing the organizational capacity of Institutional Review Boards In China: a crisp-set Qualitative Comparative Analysis based on 107 cases.

BACKGROUND: Institutional Review Boards (IRBs) play a vital role in safeguarding the rights and interests of both research participants and researchers. However, China initiated the establishment of its own IRB system relatively late in comparison to international standards. Despite commendable progress, there is a pressing need to strengthen the organizational capacity building of Chinese IRBs. Hence, this study aims to analyze the key factors driving the enhancement of organizational capacity within these committees. METHOD: The cross-sectional survey for this research was conducted from July 2020 to January 2022. Following the statistical grouping based on the "2020 China Health Statistical Yearbook", a systematic investigation of IRBs in various provinces of China was carried out. In-depth interviews and questionnaire surveys were conducted with the chairpersons and administrative executives (or secretaries) of highly cooperative IRBs. Subsequently, data were collected from 107 IRBs. Qualitative Comparative Analysis (QCA) was employed as the method to analyze the factors influencing the organizational capacity of medical ethics committees and explore the diverse combinations of these factors. RESULTS: Through a singular necessary condition analysis, the variable "protection of rights and interests" emerges as a critical factor contributing to the robust construction of Institutional Review Boards Institutional Review Boards (IRBs). Conversely, the variables of "lack of member ability, absence of review process, and deficiency in the supervision mechanism" collectively constitute a sufficient condition leading to weaker IRB construction. The state analysis uncovers three interpretation modes: member ability-oriented (M1), system process-oriented mode (M2), and resource system-oriented mode (M3). CONCLUSIONS: The results of this study are effectively explicable using the "Triangular Force" model proposed for the hypothesis of IRBs' organizational capacity, which provides a solid foundation for the development of organizational capabilities in IRBs. To enhance the organizational capacity of IRBs in China, it is imperative to elevate the competence of committee members and strengthen team development. This can be achieved by establishing a comprehensive regulatory framework and refining procedural protocols. Moreover, clarifying the organizational structure and optimizing resource allocation are essential steps in bolstering the overall organizational capabilities of these committees.

TIVC: An Efficient Local Search Algorithm for Minimum Vertex Cover in Large Graphs.

The minimum vertex cover (MVC) problem is a canonical NP-hard combinatorial optimization problem aiming to find the smallest set of vertices such that every edge has at least one endpoint in the set. This problem has extensive applications in cybersecurity, scheduling, and monitoring link failures in wireless sensor networks (WSNs). Numerous local search algorithms have been proposed to obtain "good" vertex coverage. However, due to the NP-hard nature, it is challenging to efficiently solve the MVC problem, especially on large graphs. In this paper, we propose an efficient local search algorithm for MVC called TIVC, which is based on two main ideas: a 3-improvements (TI) framework with a tiny perturbation and edge selection strategy. We conducted experiments on real-world large instances of a massive graph benchmark. Compared with three state-of-the-art MVC algorithms, TIVC shows superior performance in accuracy and possesses a remarkable ability to identify significantly smaller vertex covers on many graphs.

Cross-Inhibitor: a time-sensitive molecular circuit based on DNA strand displacement.

Designing biochemical systems that can be effectively used in diverse fields, including diagnostics, molecular computing and nanomachines, has long been recognized as an important goal of molecular programming and DNA nanotechnology. A key issue in the development of such practical devices on the nanoscale lies in the development of biochemical components with information-processing capacity. In this article, we propose a molecular device that utilizes DNA strand displacement networks and allows interactive inhibition between two input signals; thus, it is termed a cross-inhibitor. More specifically, the device supplies each input signal with a processor such that the processing of one input signal will interdict the signal of the other. Biochemical experiments are conducted to analyze the interdiction performance with regard to effectiveness, stability and controllability. To illustrate its feasibility, a biochemical framework grounded in this mechanism is presented to determine the winner of a tic-tac-toe game. Our results highlight the potential for DNA strand displacement cascades to act as signal controllers and event triggers to endow molecular systems with the capability of controlling and detecting events and signals.

Adaptive weighted Gerchberg-Saxton algorithm for generation of phase-only hologram with artifacts suppression.

In the conventional weighted Gerchberg-Saxton (GS) algorithm, the feedback is used to accelerate the convergence. However, it will lead to the iteration divergence. To solve this issue, an adaptive weighted GS algorithm is proposed in this paper. By replacing the conventional feedback with our designed feedback, the convergence can be ensured in the proposed method. Compared with the traditional GS iteration method, the proposed method improves the peak signal-noise ratio of the reconstructed image with 4.8 dB on average. Moreover, an approximate quadratic phase is proposed to suppress the artifacts in optical reconstruction. Therefore, a high-quality image can be reconstructed without the artifacts in our designed Argument Reality device. Both numerical simulations and optical experiments have validated the effectiveness of the proposed method.

Two-dimensional angle multiplexing by segmented spherical holography.

The crosstalk noise produced in the multiplexing technology of curved computer-generated holograms has caused great damage to reconstructed objects. In order to solve this problem, we propose a method to realize three-dimensional object reconstruction with low crosstalk noise impact. By multiplexing the spherical holograms in the horizontal and vertical directions, the complex amplitudes of the multiple spherical holograms with different curvatures are added to form a composed hologram. The generated hologram records many unrelated scenes of the object. According to the different angles used to generate the hologram, the original object under different viewpoints can be rebuilt, and the multiview multiplexing and reconstruction of three-dimensional objects can be realized. Simulation and optical experiments verify the feasibility of this method.

In vitro fermentation and isolation of heparin-degrading bacteria from human gut microbiota.

Heparin and its derivative are commonly used as injectable anticoagulants in clinical procedures, but possess poor oral bioavailability. To explore the role of gut microbiota in the poor oral effect of heparin, the degradation profiles of heparin on six human gut microbiota were investigated. The heparin-degradation ability varied significantly among individuals. Furthermore, two strains of heparin-degrading bacteria, Bacteroides ovatus A2 and Bacteroides cellulosilyticus B19, were isolated from the gut microbiota of different individuals and the degradation products of the isolates were profiled. The ΔUA2S-GlcNS6S was the major end product with almost no desulfation. 3-O-sulfo group-containing tetrasaccharides were detected, which indicated that the antithrombin binding site was broken and this explained the lost anticoagulant activity of heparin. Collectively, the present study assessed the degradation profiles of heparin by human gut microbiota and provided references for the development of oral administration of heparin from a gut microbiota perspective.

Effects of Layer-Charge Distribution of 2:1 Clay Minerals on Methane Hydrate Formation: A Molecular Dynamics Simulation Study.

Molecular dynamics simulations were used to investigate the effects of the external surface of a 2:1 clay mineral with different charge amounts and charge locations on CH4 hydrate formation. The results showed that 512, 51262, 51263, and 51264 were formed away from the clay mineral surface. The surface of the clay mineral with high- and low-charge layers was occupied by Na+ to form various distributions of outer- and inner-sphere hydration structures, respectively. The adsorbed Na+ on the high-charge layer surface reduced the H2O activity by disturbing the hydrogen bond network, resulting in low tetrahedral arrangement of H2O molecules near the layer surface, which inhibited CH4 hydrate formation. However, more CH4 molecules were adsorbed onto the vacancy in the Si-O rings of a neutral-charge layer to form semicage structures. Thus, the order parameter of H2O molecules near this surface indicated that the arrangement of H2O molecules resulted in a more optimal tetrahedral structure for CH4 hydrate formation than that near the negatively charged layer surface. Different nucleation mechanisms of the CH4 hydrate on external surfaces of clay mineral models were observed. For clay minerals with negatively charged layers (i.e., high and low charge), the homogeneous nucleation of the CH4 hydrate occurred away from the surface. For a clay mineral with a neutral-charge layer, the CH4 hydrate could nucleate either in the bulk-like solution homogeneously or at the clay mineral-H2O interface heterogeneously.

Automatic Fiber Length Measurements with a Multi-Stencil Fast Marching Method on Microscopy Images.

Fiber length has a strong impact on the mechanical properties of composite materials. It is one of the most important quantitative features in characterizing microstructures for understanding the material performance. Studies conducted to determine fiber length distribution have primarily focused on sample preparation and fiber dispersion. However, the subsequent image analysis is frequently performed manually or semi-automatically, which either requires careful sample preparation or manual intervention in the image analysis and processing. In this article, an image processing and analysis method has been developed based on medial axis transformation via the multi-stencil fast marching method for fiber length measurements on acquired microscopy images. The developed method can be implemented fully automatically and without any user induced delays. This method offers high efficiency, sub-pixel accuracy, and excellent statistical representativity.

RNA-Seq analysis reveals the potential molecular mechanisms of daidzein on adipogenesis in subcutaneous adipose tissue of finishing Xianan beef cattle.

Daidzein has been reported to be effective in regulating lipid metabolism in animals. However, the molecular mechanisms of daidzein on adipogenesis in beef cattle are not yet reported and the results of daidzein on affecting lipid metabolism in other species have been conflicting. High-throughput sequencing of mRNA (RNA-Seq) technology was performed to elucidate the underlying molecular mechanisms of daidzein on adipogenesis in subcutaneous adipose tissue of finishing Xianan beef cattle. A total of 893 differentially expressed genes (DEGs) were identified by differential expression analysis, among which 405 genes were upregulated and 488 genes were downregulated. Bioinformatics analysis suggested that these DEGs were significantly enriched to the pathways related to lipid metabolism including ECM-receptor interaction, Glycolysis/Gluconeogenesis and Hedgehog signalling pathway. Daidzein significantly affected the candidate genes (Shh, Pec, Gli, Wnt6, DLK, IGFBP2, ID3 and C/EBPE) related to adipocyte differentiation. Besides, daidzein improved the ability of subcutaneous adipocytes in synthesizing triglycerides by directly using the long-chain fatty acids and enhanced the efficiency of triglyceride synthesis of subcutaneous adipocytes in Xianan steers. In conclusion, daidzein plays a positive role not only in adipogenic differentiation, but also in triglyceride synthesis in subcutaneous adipose tissue of Xianan beef cattle.

O-GlcNAc transferase activates stem-like cell potential in hepatocarcinoma through O-GlcNAcylation of eukaryotic initiation factor 4E.

O-GlcNAcylation catalysed by O-GlcNAc transferase (OGT) is a reversible post-translational modification. O-GlcNAcylation participates in transcription, epigenetic regulation, and intracellular signalling. Dysregulation of O-GlcNAcylation in response to high glucose or OGT expression has been implicated in metabolic diseases and cancer. However, the underlying mechanisms by which OGT regulates hepatoma development remain largely unknown. Here, we employed the lentiviral shRNA-based system to knockdown OGT to analyse the contribution of OGT in hepatoma cell proliferation and stem-like cell potential. The sphere-forming assay and western blot analysis of stem-related gene expression were used to evaluate stem-like cell potential of hepatoma cell. We found that the level of total O-GlcNAcylation or OGT protein was increased in hepatocellular carcinoma. OGT activated stem-like cell potential in hepatoma through eukaryotic initiation factor 4E (eIF4E) which bound to stem-related gene Sox2 5'-untranslated region. O-GlcNAcylation of eIF4E at threonine 168 and threonine 177 protected it from degradation through proteasome pathway. Expression of eIF4E in hepatoma was determined by immunostaining in 232 HCC patients, and Kaplan-Meier survival analysis was used to determine the correlation of eIF4E expression with prognosis. High glucose promoted stem-like cell potential of hepatoma cell through OGT-eIF4E axis. Collectively, our findings indicate that OGT promotes the stem-like cell potential of hepatoma cell through O-GlcNAcylation of eIF4E. These results provide a mechanism of HCC development and a cue between the pathogenesis of HCC and high glucose condition.

ß1,4-Galactosyltransferase V activates Notch1 signaling in glioma stem-like cells and promotes their transdifferentiation into endothelial cells.

Malignant glioblastoma multiforme is one of the most aggressive human cancers, with very low survival rates. Recent studies have reported that glioma stem-like cells transdifferentiate into endothelial cells, indicating a new mechanism for tumor angiogenesis and potentially providing new therapeutic options for glioblastoma treatment. Glioma malignancy is strongly associated with altered expression of N-linked oligosaccharide structures on the cell surface. We have previously reported that ß1,4-galactosyltransferase V (ß1,4GalTV), which galactosylates the GlcNAcß1-6Man arm of the branched N-glycans, is highly expressed in glioma and promotes glioma cell growth in vitro and in vivo However, the mechanism by which ß1,4GalTV stimulates glioma growth is unknown. Here we demonstrate that short hairpin RNA-mediated ß1,4GalTV knockdown inhibits the tumorigenesis of glioma stem-like cells and reduces their transdifferentiation into endothelial cells. We also found that ß1,4GalTV overexpression increased glioma stem-like cell transdifferentiation into endothelial cells and that this effect required ß1,4GalTV galactosylation activity. Moreover, ß1,4GalTV promoted ß1,4-galactosylation of Notch1 and increased Notch1 protein levels. Of note, ectopic expression of activated Notch1 rescued the inhibitory effect of ß1,4GalTV depletion on glioma stem-like cell transdifferentiation. In summary, our findings indicate that ß1,4GalTV stimulates transdifferentiation of glioma stem-like cells into endothelial cells by activating Notch1 signaling. These detailed insights shed important light on the mechanisms regulating glioma angiogenesis.

Fast hologram generation using intermediate angular-spectrum method for high-quality compact on-axis holographic display.

In the angular-spectrum method-based computer-generated hologram, the zero-padding method is used to convert circular convolution into linear convolution. However, it will increase the calculation time and memory usage significantly. Therefore, a fast and simple method is proposed to solve the issue of the numerical convolution in the process of hologram generation by using the intermediate angular-spectrum method in this paper. Through replacing numerical Fourier transform by optical Fourier transform in the hologram generation, the calculation speed is approximately 6 times faster than that of the zero-padding method. And due to the scaling factors introduced by the Fourier lens and without the cropping operation, the reconstruction quality of the proposed method is improved significantly compared with the zero-padding method. Moreover, the optical reconstruction system is more compact than the 4-f filter system in the on-axis holographic reconstruction. Both numerical simulations and optical experiments have validated the effectiveness of the proposed method.

The abnormal function of CD39+ regulatory T cells could be corrected by high-dose dexamethasone in patients with primary immune thrombocytopenia.

Primary immune thrombocytopenia is an autoimmune disease, characterized with decreased platelet and increased risk of bleeding. Recent studies have shown the reduction and dysfunction of regulatory T (Treg) cells in ITP patients. CD39 is highly expressed on the surface of Treg cells. It degrades ATP to AMP and CD73 dephosphorylates AMP into adenosine. Then adenosine binds with adenosine receptor and suppresses immune response by activating Treg cells and inhibiting the release of inflammatory cytokines from effector T (Teff) cells. Adenosine receptor has several subtypes and adenosine A2A receptor (A2AR) plays a crucial role especially within lymphocytes. The CD39+ Treg cells and the expression of A2AR showed abnormality in some autoimmune disease. But knowledge of CD39+ Treg cells and A2AR which are crucial in the adenosine immunosuppressive pathway is still limited in ITP. Thirty-one adult patients with newly diagnosed ITP were enrolled in this study. CD39 and A2AR expression was measured by flow cytometry and RT-PCR. The function of CD39 was reflected by the change of ATP concentration detected by CellTiter-Glo Luminescent Cell Viability Assay. CD39 expression within CD4+CD25+ Treg cells in ITP patients was decreased compared to normal controls. After high-dose dexamethasone therapy, response (R) group showed increased CD39 expression within Treg cells while non-response (NR) group did not show any difference in contrast to those before treatment. The expression of A2AR in CD4+CD25- Teff and CD4+CD25+ Treg cells was both lower in ITP patients than that of normal controls. After therapy, CD4+CD25- Teff cells had higher A2AR expression while CD4+CD25+ Treg cells did not show any difference in comparison to that before treatment. The enzymatic activity of CD39 was damaged in ITP patients and improved after high-dose dexamethasone therapy. In ITP, there was not only numerical decrease but also impaired enzymatic activity in CD39+ Treg cells. After high-dose dexamethasone treatment, these two defects could be reversed. Our results also suggested that ITP patients had reduced A2AR expression in both CD4+CD25+ Treg cells and CD4+CD25- Teff cells. CD4+CD25- Teff cells had increased A2AR expression after treatment.

Distinct alterations of CD68+CD163+ M2-like macrophages and myeloid-derived suppressor cells in newly diagnosed primary immune thrombocytopenia with or without CR after high-dose dexamethasone treatment.

BACKGROUND: Although impaired myeloid-derived suppressor cells (MDSCs) recently have been studied in immune thrombocytopenia (ITP), another myeloid-derived cell population signified as M2 macrophages has not been investigated properly in ITP patients. In the present study, we intended to determine the features of circulating M2-like macrophages, to examine its relationship with MDSCs, and to explore their prognostic values in ITP. METHODS: Peripheral blood mononuclear cells from healthy controls and primary ITP patients were isolated to test the circulating M2-like macrophages and MDSCs. The circulating M2-like macrophage population defined as CD68+CD163+ and circulating MDSC population as CD11b+CD33+HLA-DR- were determined by flow cytometry. Plasma inflammatory cytokines were measured by multiplex ELISA. RESULTS: The percentages of MDSCs were found to be expanded in newly diagnosed patients of ITP, especially among those of the complete response (CR) group (p < 0.0001). Positive linear correlation was verified between percentages of M2-like macrophages and MDSCs. The same correlation was also determined in the CR group. After treatment, the percentages of M2-like macrophages and MDSCs were both increased significantly in CR group, while those patients among the PR + NR group manifested a significant numeric decrease of MDSCs but only a moderate decrease in M2-like macrophages. MIP-1α/CCL3 was negatively correlated with M2-like macrophages while MCP-1 possessed a positive correlation with M2-like macrophages, eotaxin-1/CCL11 was negatively correlated with MDSCs and interleukin-1ß (IL-1ß) was found to be negatively correlated with both M2-like macrophages and MDSCs. CONCLUSIONS: The present findings indicated critical roles of both circulating M2-like macrophages and MDSCs in ITP. The positive correlation between them might be related to inflammatory factors-mediated bidirectional interactions or partially due to their similar background patterns during differentiation. MIP-1α/CCL3, MCP-1, eotaxin-1/CCL11 and IL-1ß might play a critical role in the expansion of both M2 macrophages and MDSCs population in ITP patients, which deserves further investigation.

Stability of Polydopamine Coatings on Gold Substrates Inspected by Surface Plasmon Resonance Imaging.

Polydopamine (PDA)-based surface modification has been used in a variety of fields. However, a vague impression on the stability of PDA still exists due to a lack of systematic studies. To ascertain the issue and make better use of this surface modification method, a technique of surface plasmon resonance imaging (SPRi) was exploited to study the stability of PDA coated on gold surface. The results showed that PDA-coating stability was largely dependent on the pH of aqueous solutions, giving detachment ratios up to 66% and 80% at pH 1.0 and pH 14.0, respectively. However, increasing the ionic strength of aqueous solutions could reduce the detachment of PDA in strong acid and strong alkali conditions. Besides, organic solvents also made a difference on the PDA-coating stability. Among the tested 10 kinds of organic solvents, including n-hexane, toluene, ethyl ether, tetrahydrofuran, ethyl acetate, isopropanol, acetone, acetonitrile, dimethylformamide (DMF), and dimethyl sulfoxide (DMSO), DMSO caused the most serious detachment of PDA, up to 56%, followed by DMF with a detachment ratio of 31%. Ultrasonication caused less than 10% detachment of the coated PDA. It should be mentioned that the PDA coatings deposited on gold surface were not detached completely in all the test conditions, even at pH 14.0 (ca. 20% PDA retained). In alkaline conditions, detachment competes with further polymerization, which gave a slight increase of the SPRi signals at pH 9.0-11.0. Based on the obtained information about PDA-coating stability, thickness-controllable and alkali-resistant PDA coatings were prepared. Moreover, the alkali-resistant PDA coatings remained reactive to biomolecules, supporting further functionalization of PDA coatings.