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Background: Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer with major challenges in both prevention and therapy. Metformin, adenosine monophosphate‐activated protein kinase (AMPK) activator, has been suggested to reduce the incidence of HCC when used for patients with diabetes in preclinical and clinical studies. However, the possible effects of metformin and their mechanisms of action in non‐diabetic HCC have not been adequately investigated. Methods: Fah−/− mice were used to construct a liver‐injury‐induced non‐diabetic HCC model for exploring hepatocarcinogenesis and therapeutic potential of metformin. Changes in relevant tumour and biochemical indicators were measured. Bulk and single‐cell RNA‐sequencing analyses were performed to validate the crucial role of proinflammatory/pro‐tumour CD8+ T cells. In vitro and in vivo experiments were performed to confirm Cyp26a1‐related antitumour mechanisms of metformin. Results: RNA‐sequencing analysis showed that chronic liver injury led to significant changes in AMPK‐, glucose‐ and retinol metabolism‐related pathways in Fah−/− mice. Metformin prevented the formation of non‐diabetic HCC in Fah−/− mice with chronic liver injury. Cyp26a1 ddexpression in hepatocytes was significantly suppressed after metformin treatment. Moreover, downregulation of Cyp26a1 occurred in conjunction with increased levels of all‐trans‐retinoic acid (atRA), which is involved in the activation of metformin‐suppressed hepatocarcinogenesis in Fah−/− mice. In contrast, both CD8+ T‐cell infiltration and proinflammatory/pro‐tumour cytokines in the liver were significantly upregulated in Fah−/− mice during chronic liver injury, which was notably reversed by either metformin or atRA treatment. Regarding mechanisms, metformin regulated the decrease in Cyp26a1 enzyme expression and increased atRA expression via the AMPK/STAT3/Gadd45β/JNK/c‐Jun pathway. Conclusions: Metformin inhibits non‐diabetic HCC by upregulating atRA levels and downregulating CD8+ T cells. This is the first reporting that the traditional drug metformin regulates the metabolite atRA via the Cyp26a1‐involved pathway. The present study provides a potential application of metformin and atRA in non‐diabetic HCC. [ABSTRACT FROM AUTHOR]

Although lithofacies routinely is featured by distinct logging responses from each other, many types of lithofacies in practical cases show similar measuring characteristics on logs, and then to achieve a desirable solution from logging‐based lithofacies prediction actually is challengeable. Since the mathematical essence of lithofacies prediction can be explained as an issue of pattern recognition, a light gradient boosting machine, a state‐of‐the‐art ensemble learning, specifically developed to address supervised classification, could be a potential solver. Nonetheless, due to an incompatibility of inherent exclusive feature bundling algorithm for logs and usage of a great deal of hyper‐parameters, a raw light gradient boosting machine might not be suitable or functional to predict lithofacies. Thus, continuous restricted Boltzmann machine and Bayesian optimization, respectively, employed to process original logging data and optimize hyper‐parameters, are adopted as technical assistants for the light gradient boosting machine, and accordingly a new ensemble learning‐based predictor called continuous restricted Boltzmann machine – Bayesian optimization – the light gradient boosting machine, is proposed for lithofacies. To validate classifying capability and robust nature of new predictor, three experiments are designed purposefully based on the application of a dataset collected from the wells located within pre‐salt lacustrine carbonate reservoirs of the Santos Basin. Simultaneously, to highlight validating effect, other three sophisticated classifiers are introduced as competitors in all experiments, including supper vector machine, random forest and extreme gradient boosting. According to the analysis and comparison of all experimental results, overall four points are verified: (1) the integration of continuous restricted Boltzmann machine and Bayesian optimization indeed is beneficial for the light gradient boosting machine in data preprocess and modelling stage; (2) the light gradient boosting machine cored predictor shows more capability of producing reliable predicted lithofacies information compared to other three competitors; (3) training more learning samples is a simple and effective approach to enhance computing capability of any validated predictor, and under this circumstance the light gradient boosting machine cored predictor still performs relatively better; (4) the light gradient boosting machine cored predictor is characterized with a better robustness as its predicting outcomes, even derived from a sparse‐condition dataset, are also proved more qualified. Consequently, the new proposed predictor is demonstrated as a high‐efficient and robust solver for the prediction of lithofacies and deserves a widespread application in the geological, geophysical and petrophysical research. [ABSTRACT FROM AUTHOR]

This study implements the least-squares inversion method for solving the exhumation history from thermochornologic age-elevation relationship (AER) based on the linear equation among exhumation rate, thermochronologic age and total exhumation from the closure depth to the Earth surface. Modelling experiments demonstrate the significant and systematic influence of initial geothermal model, the a priori exhumation rate and the time interval length on the a posterior exhumation history. Lessons learned from the experiments include that (i) the modern geothermal gradient can be used for constraining the initial geothermal model, (ii) a relatively higher a priori exhumation rate would lead to systematically lower inversion results, and vice versa , (iii) the variance of the a priori exhumation rate controls the variation of the inverted exhumation history, (iv) the choice of time interval length should be optimized for resolving the potential temporal changes in exhumation. Putting together these findings, we propose a new stepwise inversion modeling strategy for optimizing the model parameters to mitigate the model dependencies on the initial parameters. Finally, we use three examples of different exhumation rates and histories for method demonstration. It is shown that our new modelling strategy produces geologically reasonable exhumation histories and geothermal gradients that are consistent with both the observed AER and modern geothermal data. The code and data used in this work is available in GitHub (https://github.com/yuntao-github/code4modelAER). [ABSTRACT FROM AUTHOR]

Developing high‐efficient photocatalysts for H2 production is still the focus of current research. A series of CoSx/Zn0.3Cd0.7S (CoSx/ZCS) samples with different mass ratios were successfully synthesized for H2 production by the oxidation of p‐chlorobenzyl alcohol (Cl‐PhCH2OH). Herein, Zn0.3Cd0.7S (ZCS) solid‐solution nanoparticles are distributed on the surface of CoSx polyhedron, and CoSx is obtained from ZIF‐67, composed of Co1−xS and CoS2. The photocatalytic H2 production was performed by Cl‐PhCH2OH oxidation in N,N‐Dimethylformamide (DMF) solution under visible light irradiation, and 5% CoSx/ZCS sample showed the best photocatalytic activity, with the H2 generated rate high to 2.80 mmol g−1 h−1. Meanwhile, the selectivity of Cl‐PhCH2OH oxidation to p‐chlorobenzaldehyde (Cl‐PhCHO) is 97.6%, and the rate is 2.95 mmol g−1 h−1. Moreover, the reasons for the excellent photocatalytic performance of CoSx/ZCS samples were deeply analyzed by experimental and theoretical results, such as trapping agents, photoelectrochemistry test, electron paramagnetic resonance (EPR), specific surface area, and density functional theory (DFT) calculation. This work provides a new theoretical guidance and experimental experience for the application of H2 application and design of novel photocatalysts. [ABSTRACT FROM AUTHOR]

Background Accurate evaluation of the activity stage in Takayasu arteritis (TA) is important for the revascularization of TA with coronary artery involvement (TA-CAD). Here, we report the case of a patient with a mismatch of systemic and local inflammatory activity, leading to 13 times the need for recurrent coronary revascularization. Case summary A 31-year-old woman with a family history of coronary artery disease underwent percutaneous coronary intervention (PCI) for critical ostial lesions. This patient was identified with Numano Type V TA and she underwent optimal medical therapy and PCIs. Her clinical inflammatory markers were quickly normalized. However, in-stent restenosis events recurred every 3 months. Virtual-histology intravascular ultrasound (VH-IVUS) and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) confirmed local vascular inflammation. A coronary artery bypass graft (CABG) was also conducted. Before this procedure, both the CABG grafts and the anastomotic areas were accurately assessed with 18FDG-PET/CT. Eventually, this patient remained both angina- and event-free for 2 years post-CABG. Discussion The persistence of TA activity despite normal clinical inflammatory markers is uncommon as is the need for recurrent revascularization after appropriate PCI management. Intracoronary imaging and 18FDG-PET/CT play a critical role in assessing TA activity as well as precisely guiding CABG grafts and anastomosis sites to prevent graft failure. [ABSTRACT FROM AUTHOR]