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In recent years, safety issues respecting polar ship navigation in the presence of ice have become a research hotspot. The accurate prediction of propulsion power plays an important role in ensuring safe ship navigation and evaluating ship navigation ability, and deep learning has been widely applied in the field of shipping, of which the artificial neural network (ANN) is a common method. This study combines the scientific problems of ice resistance and propulsion power for polar ship design, focusing on the design of an ANN model for predicting the propulsion power of polar ships. Reference is made to the traditional propulsion power requirements of various classification societies, as well as ship model test and full-scale test data, to select appropriate input features and a training dataset. Three prediction methods are considered: building a radial basis function–particle swarm optimization algorithm (RBF-PSO) model to directly predict the propulsion power; based on the full-scale test and model test data, calculating the propulsion power using the Finnish–Swedish Ice Class Rules (FSICR) formula; using an ice resistance artificial neural network model (ANN-IR) to predict the ice resistance and calculate the propulsion power using the FSICR formula. Prediction errors are determined, and a sensitivity analysis is carried out with respect to the relevant parameters of propulsion power based on the above methods. This study shows that the RBF-PSO model based on nine feature inputs has a reasonable generalization effect. Compared with the data of the ship model test and full-scale test, the average error is about 14%, which shows that the method has high accuracy and can be used as a propulsion power prediction tool.

Currently there is no standard therapy recommended for second-line treatment for thymic carcinoma. Our study compared multidrug chemotherapy, single-agent chemotherapy, and PD-1 inhibitors in patients diagnosed with advanced thymic carcinoma who had previous platinum-based chemotherapy at the clinic.The study included patients with thymic carcinoma who failed first-line platinum-based chemotherapy. Kaplan-Meier methods were applied in the study for estimating the progression-free survival (PFS) and overall survival (OS) curves. Pearson chi-square or Fisher's exact chi-square test was adopted to make comparisons of the objective response rate (ORR) between treatment groups. Cox regression was used for the multivariate analyses in PFS and OS.Among the 92 patients enrolled, multidrug chemotherapy was used in 51 (55.4%) patients for second-line therapy. Thirty-six patients (35.9%) received single-agent chemotherapy, and eight patients (8.7%) underwent PD-1 inhibitors. The multidrug chemotherapy group showed better efficacy than the other two groups, with an ORR of 35.3% (p = 0.006). The median PFS of multidrug chemotherapy, single-agent chemotherapy and PD-1 inhibitors were 5.0 months, 3.0 months, and 4.0 months, respectively (p = 0.008). Patients in the multidrug chemotherapy group also showed an advantage in OS in comparison with the other two treatment groups (p = 0.045), with a median OS of 30.4 months. Multivariate analysis showed that second-line treatment was independent factor for both PFS (p = 0.035) and OS (p = 0.037). Grade 3-4 AEs were mostly detected in patients receiving multidrug chemotherapy and were primarily hematologic. Treatment-related mortality was not found in any of the groups.Multidrug chemotherapy had a trend toward a more positive response rate and outcomes in longer survival time than single-agent chemotherapy and PD-1 inhibitors. Multidrug chemotherapy is a choice worth considering for second-line therapy in patients with thymic carcinoma if tolerable.

Background Lung Adenocarcinoma (LUAD) is a major component of lung cancer. Endoplasmic reticulum stress (ERS) has emerged as a new target for some tumor treatments. Methods The expression and clinical data of LUAD samples were downloaded from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO) database, followed by acquiring ERS-related genes (ERSGs) from the GeneCards database. Differentially expressed endoplasmic reticulum stress-related genes (DE-ERSGs) were screened and used to construct a risk model by Cox regression analysis. Kaplan–Meier (K-M) curves and receiver operating characteristic (ROC) curves were plotted to determine the risk validity of the model. Moreover, enrichment analysis of differentially expressed genes (DEGs) between the high- and low- risk groups was conducted to investigate the functions related to the risk model. Furthermore, the differences in ERS status, vascular-related genes, tumor mutation burden (TMB), immunotherapy response, chemotherapy drug sensitivity and other indicators between the high- and low- risk groups were studied. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the mRNA expression levels of prognostic model genes. Results A total of 81 DE-ERSGs were identified in the TCGA-LUAD dataset, and a risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was constructed by Cox regression analysis. K-M and ROC analyses showed that the high-risk group had a low survival, and the Area Under Curve (AUC) of ROC curves of 1-, 3- and 5-years overall survival was all greater than 0.6. In addition, functional enrichment analysis suggested that the risk model was related to collagen and extracellular matrix. Furthermore, differential analysis showed vascular-related genes FLT1, TMB, neoantigen, PD-L1 protein (CD274), Tumor Immune Dysfunction and Exclusion (TIDE), and T cell exclusion score were significantly different between the high- and low-risk groups. Finally, qRT-PCR results showed that the mRNA expression levels of 6 prognostic genes were consistent with the analysis. Conclusion A novel ERS-related risk model, including HSPD1, PCSK9, GRIA1, MAOB, COL1A1, and CAV1, was developed and validated, which provided a theoretical basis and reference value for ERS-related fields in the study and treatment of LUAD.

Background Tyrosine kinase inhibitors (TKIs) are anti-cancer therapeutics often prescribed for long-term treatment. Many of these treatments cause cardiotoxicity with limited cure. We aim to clarify molecular mechanisms of TKI-induced cardiotoxicity so as to find potential targets for treating the adverse cardiac complications. Methods Eight TKIs with different levels of cardiotoxicity reported are selected. Phenotypic and transcriptomic responses of human cardiomyocytes to TKIs at varying doses and times are profiled and analyzed. Stress responses and signaling pathways that modulate cardiotoxicity induced by three TKIs are validated in cardiomyocytes and rat hearts. Results Toxicity rank of the eight TKIs determined by measuring their effects on cell viability, contractility, and respiration is largely consistent with that derived from database or literature, indicating that human cardiomyocytes are a good cellular model for studying cardiotoxicity. When transcriptomes are measured for selected TKI treatments with different levels of toxicity in human cardiomyocytes, the data are classified into 7 clusters with mainly single-drug clusters. Drug-specific effects on the transcriptome dominate over dose-, time- or toxicity-dependent effects. Two clusters with three TKIs (afatinib, ponatinib, and sorafenib) have the top enriched pathway as the endoplasmic reticulum stress (ERS). All three TKIs induce ERS in rat primary cardiomyocytes and ponatinib activates the IRE1α-XBP1s axis downstream of ERS in the hearts of rats underwent a 7-day course of drug treatment. To look for potential triggers of ERS, we find that the three TKIs induce transient reactive oxygen species followed by lipid peroxidation. Inhibiting either PERK or IRE1α downstream of ERS blocks TKI-induced cardiac damages, represented by the induction of cardiac fetal and pro-inflammatory genes without causing more cell death. Conclusions Our data contain rich information about phenotypic and transcriptional responses of human cardiomyocytes to eight TKIs, uncovering potential molecular mechanisms in modulating cardiotoxicity. ER stress is activated by multiple TKIs and leads to cardiotoxicity through promoting expression of pro-inflammatory factors and cardiac fetal genes. ER stress-induced inflammation is a promising therapeutic target to mitigate ponatinib- and sorafenib-induced cardiotoxicity. Graphical Abstract

Fusarium pseudograminearum is a soil-borne pathogen that is capable of causing a highly destructive crown disease in wheat. Secondary metabolites (SMs), especially deoxynivalenol (DON), are the primary virulence factors during infection. Here, we characterised the global regulator FpLaeB, an orthologue of LaeB protein function, to regulate the SM in Aspergillus nidulans. Through the utility of the gene targeting approach, we found that the vegetative growth of the FpLaeB deletion mutant was drastically reduced compared to that of the wild type. FpLaeB was also important for conidiation because the FpLaeB deletion mutant formed fewer conidia in induced medium. In addition, the sensitivity of the FpLaeB deletion mutant to the cell wall integrity inhibitor was decreased, while its growth was more severely inhibited by the cell membrane inhibitor sodium dodecyl sulfate (SDS) than that of the wild type. More importantly, the virulence was decreased when the FpLaeB deletion mutant was inoculated onto the wheat stem base or head. Through genome-wide gene expression profiling, FpLaeB was found to regulate several processes related to the above phenotypes such as the carbohydrate metabolic process, which is an integral and intrinsic component of membranes, especially SMs. Furthermore, the generation of DON was impaired in the FpLaeB deletion mutant via ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay. These results showed that FpLaeB plays an important role in the growth, development, and maintenance of the cell wall, and in membrane integrity. More importantly, FpLaeB is required for SMs and full virulence in F. pseudograminearum.

Accurate segmentation of prostate region is an important prerequisite to improve the accuracy of computer-aided prostate cancer diagnosis. In this work, a new and accurate prostate segmentation algorithm is proposed and tested. The new algorithm consists of 4 steps: reading T2-weighted magnetic resonance images, calculating local binary pattern (LBP) feature map of prostate magnetic resonance images by using an 8x5 LBP feature template, segmenting the feature map with the improved distance regularization level set evolution (DRLSE) algorithm, and extracting coarse contour of the prostate. A new energy function is constructed to extract local gray scale information and gradient information, and the coarse contour is iteratively developed into the final fine prostate contour on the basis of this new energy function. The algorithm was tested with the SPIE-AAPM-NCI Prostate MR Classification Challenge Database. The segmentation results of the proposed algorithm were compared with that of manual segmentation by doctors. The results showed that the Dice coefficient obtained by using the proposed algorithm was 0.94±0.01, with a relative volume difference (RVD) of -1.21%±2.44% and a 95% Hausdorff distance (HD) of 6.15±0.66 mm. Compared with the existing segmentation algorithms, the segmentation results obtained with the algorithm proposed in this paper are closer to the manual segmentation results.

BACKGROUND AND AIMS Chronic alcohol drinking is a major risk factor for alcohol-associated liver disease (ALD). FK506-binding protein 51 (FKBP5), a cochaperone protein, is involved in many key regulatory pathways. It is known to be involved in stress-related disorders, but there are no reports regarding its role in ALD. This present study aimed to examine the molecular mechanism of FKBP5 in ALD. APPROACH AND RESULTS We found a significant increase in hepatic FKBP5 transcripts and protein expression in patients with ALD and mice fed with chronic-plus-single binge ethanol. Loss of Fkbp5 in mice protected against alcohol-induced hepatic steatosis and inflammation. Transcriptomic analysis revealed a significant reduction of Transcriptional enhancer factor TEF-1 (TEA) domain transcription factor 1 (Tead1) and chemokine (C-X-C motif) ligand 1 (Cxcl1) mRNA in ethanol-fed Fkbp5-/- mice. Ethanol-induced Fkbp5 expression was secondary to down-regulation of methylation level at its 5' untranslated promoter region. The increase in Fkbp5 expression led to induction in transcription factor TEAD1 through Hippo signaling pathway. Fkbp5 can interact with yes-associated protein (YAP) upstream kinase, mammalian Ste20-like kinase 1 (MST1), affecting its ability to phosphorylate YAP and the inhibitory effect of hepatic YAP phosphorylation by ethanol leading to YAP nuclear translocation and TEAD1 activation. Activation of TEAD1 led to increased expression of its target, CXCL1, a chemokine-mediated neutrophil recruitment, causing hepatic inflammation and neutrophil infiltration in our mouse model. CONCLUSIONS We identified an FKBP5-YAP-TEAD1-CXCL1 axis in the pathogenesis of ALD. Loss of FKBP5 ameliorates alcohol-induced liver injury through the Hippo pathway and CXCL1 signaling, suggesting its potential role as a target for the treatment of ALD.

This study evaluated the effects of the types (MFL and acetate anti-icing filler) and the replacement rate of anti-icing additives on the performance of asphalt mixtures. Additionally, the road performance as well as ice inhibition capacity between environmental (acetate anti-icing filler) and conventional (MFL) anti-icing materials were compared. The equivalent volume displacement method was applied to determine the amount of anti-icing filler in asphalt mixture. In this paper, the high-temperature stability, low-temperature bending properties, water stability, ice inhibition properties and anti-icing persistence of the mixture were investigated in the laboratory. The results show that the ice inhibitor has negative effects on the rutting resistance, crack resistance and moisture sensitivity of the asphalt mixture. Additionally, the adverse effects become more obvious as the replacement rate increases. There was a similar trend in the mixtures with three kinds of ice inhibition filler in general. The tests also proved that the anti-icing fillers can effectively delay and inhibit the occurrence of road icing, weaken the bonding force between pavement surface and the ice layer and make the ice layer easy to be removed. It is found that the comprehensive performance of traditional ice inhibitors is better. Moreover, the high-temperature stability, anti-icing capacity and ice inhibition persistence of environmentally friendly anti-icing additives need to be improved.

To successfully analyze complex samples and detect trace targets, sample pretreatment is essential. Efficient sample pretreatment techniques can remove or reduce interference from the sample matrix. It can also enrich analytes, thereby improving analytical accuracy and sensitivity. In recent years, various sample preparation techniques, including SPE, magnetic dispersion SPE, pipette tip SPE, stir bar extraction, fiber SPME, and in-tube SPME, have received increasing attention in environmental analysis and monitoring. The extraction efficiency mainly depends on the type of adsorbent material. Therefore, the development of efficient adsorbents is a crucial step toward sample preparation. This review summarizes and discusses the research advances in extraction materials over recent years. These extraction materials contain inorganic adsorbents, organic adsorbents, and inorganic-organic hybrid materials such as graphene, graphene oxide, carbon nanotubes, inorganic aerogels, organic aerogels, triazinyl-functionalized materials, triazine-based polymers, molecularly imprinted polymers, covalent organic frameworks, metal-organic frameworks, and their derivatives. These materials have been applied to extract different types of pollutants, including metal ions, polycyclic aromatic hydrocarbons, plasticizers, alkanes, phenols, chlorophenols, chlorobenzenes, polybrominated diphenyl ethers, perfluorosulfonic acids, perfluorocarboxylic acids, estrogens, drug residues, and pesticide residues, from environmental samples (such as water and soil samples). These sample preparation materials possess high surface areas, numerous adsorption sites, and allow extraction via various mechanisms, such as π-π, electrostatic, hydrophobic, and hydrophilic interactions, as well as hydrogen and halogen bond formation. Various sample pretreatment techniques based on these extraction materials have been combined with various detection methods, including chromatography, mass spectrometry, atomic absorption spectroscopy, fluorescence spectroscopy, and ion mobility spectroscopy, and have been extensively used for the determination of environmental pollutants. The existing challenges associated with the development of sample preparation techniques are proposed, and prospects for such extraction materials in environmental analysis and monitoring are discussed. Major trends in the field, including the development of efficient extraction materials with high enrichment ability, good selectivity, excellent thermal stability, and chemical stability, are discussed. Green sample pretreatment materials, environmentally friendly synthesis methods, and green sample pretreatment methods are also explored. Rapid sample pretreatment methods that can be conducted within minutes or seconds are of significant interest. Further, online sample pretreatment and automatic analysis methods have attracted increasing attention. Besides, real-time analysis and in situ detection have been important development directions, and are expected to be widely applicable in environmental analysis, biological detection, and other fields. Modern synthesis technology should be introduced to synthesize specific extraction materials. Controllable preparation methods for extraction materials, such as the in situ growth or in situ preparation of extraction coatings, will acquire importance in coming years. It will also be important to adopt high-performance materials from other fields for sample pretreatment. Organic-inorganic hybrid extraction materials can combine the advantages both organic materials and inorganic materials, and mutually compensate for any disadvantages. Extraction materials doped with nanomaterials are also promising. Although existing sample pretreatment techniques are relatively efficient, it is still imperative to develop novel sample preparation methods.

Objective: Hepatocellular carcinoma (HCC), the main type of liver cancer, has a high morbidity and mortality, and a poor prognosis. RNA helicase DDX5, which acts as a transcriptional co-regulator, is overexpressed in most malignant tumors and promotes cancer cell growth. Heat shock protein 90 (HSP90) is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or survival. Methods: DDX5 mRNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot, respectively. The interaction of DDX5-HSP90 was determined by molecular docking, immunoprecipitation, and laser scanning confocal microscopy. The autophagy signal was detected by Western blot. The cell functions and signaling pathways of DDX5 were determined in 2 HCC cell lines. Two different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 inhibitor. Results: HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy pathway. The subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating the β-catenin signaling pathway. The silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft model. High levels of HSP90 and DDX5 protein were associated with poor prognoses. Conclusions: HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic degradation. DDX5 and HSP90 are therefore potential therapeutic targets for HCC.

Background Endostatin and bevacizumab have been approved for the first-line treatment of advanced non-small-cell lung cancer (NSCLC) patients in China; however, the clinical outcomes for each drug combined with platinum-based doublet chemotherapy (PT-DC) have not yet been directly compared. This study sought to assess the clinical outcomes of the 2 drugs combined with PT-DC in the first-line treatment of patients with advanced lung adenocarcinoma. Methods This retrospective cohort study examined the clinical data of patients with metastatic or recurrent lung adenocarcinoma (LUAD) treated with endostatin or bevacizumab combined with PT-DC as the first-line treatment from October 2010 to November 2019. Propensity score matching (PSM) was performed using a 1:1 ratio nearest neighbor algorithm. The effectiveness and safety outcomes for the 2 groups were evaluated. Results A total of 202 patients were enrolled in the study. Of these, the endostatin group comprised 124 patients and the bevacizumab group comprised 78 patients; 67 pairs of patients were identified after PSM. The progression-free survival (PFS) and overall survival (OS) of patients treated with PT-DC + endostatin and PT-DC + bevacizumab were compared [(PFS: before PSM 4.8 vs. 6.5 months, P=0.741; after PSM 6.5 vs. 6.1 months, P=0.402), (OS: before PSM 21.1 vs. 39.3 months, P=0.912; after PSM 23.6 vs. 39.3 months, P=0.579)]. The objective response rates (ORRs) and disease control rates (DCRs) of the 2 groups were comparable (37.7% vs. 50.7%, P=0.094; 89.6% vs. 92.5%, P=0.545). Adverse events (AEs) ≥ grade 3 were not observed in the PT-DC + endostatin group. Three (3.8%) cases of AEs ≥ grade 3 were observed the PT-DC + bevacizumab group, comprising hypertension (n=1), proteinuria (n=1), hemoptysis (n=1). Conclusions This retrospective analysis showed that in first-line treatments, PT-DC + endostatin and PT-DC + bevacizumab appear to produce similar anti-tumor activities in patients with metastatic or recurrent lung adenocarcinoma. PT-DC + bevacizumab tended to result in worse adverse reactions than PT-DC + endostatin.

Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

In order to evaluate the homogeneity of asphalt mixture quantitatively, the distribution characteristic of internal phases of asphalt mixture were identified based on digital image processing technique and stereology theory, and the homogeneity coefficient (i.e., K) was proposed. At the same time, the trend of variation and reliability of homogeneity of asphalt mixture were analyzed by changing the nominal maximum aggregate size, aggregate gradation and asphalt content. The results suggest that the homogeneity of asphalt mixture could be comprehensively described using DIP technique combined with stereology theory. The smaller the K, the better the distribution homogeneity of the asphalt mixture. An improvement in the homogeneity of an asphalt mixture is achieved with the decrease of the nominal maximum aggregate size and a finer aggregate gradation. The asphalt content corresponding to the optimal homogeneity of the internal structure of asphalt mixture specimen is the optimum asphalt content. According to the experimental study, the suggested values of the homogeneity coefficient were given, which provides theoretical support to control the construction quality of the hot mixture asphalt.

Background Small cell lung cancer (SCLC) is characterized by aggressive spread and poor prognosis, but has limited treatment options. Results of prognostic factors from randomized trials on treatment arrangement are conflicting and large‐scale real‐world analysis is lacking. Methods Patients diagnosed SCLC between 2008 and 2018 in Peking University Cancer Hospital were included in this study. Kaplan–Meier methods were adopted, and univariate analysis and multivariate Cox regression models were constructed to analyze prognostic factors. Results Among 1045 patients who presented to our center, 988 eligible patients were identified. Median overall survival (OS) was 16.0 months for the whole group, 24.0 months and 11.0 months for limited stage small cell lung cancer (LS‐SCLC) and extensive stage small cell lung cancer (ES‐SCLC), separately. Limited‐stage, good performance status (PS) (ECOG 0–1), response to primary systemic treatment, and patients who received initiative irradiation and three or more lines of chemotherapy were predicted to have better OS in the whole group. Only response to first‐line systemic therapy and prophylactic cranial irradiation (PCI) were independent prognostic factors of survival in LS‐SCLC; while good PS (ECOG 0–1), without liver, bone, or subcutaneous metastases, response to first‐line therapy, initial local irradiation, and three or more lines of systemic therapy predicted a favorable prognosis in ES‐SCLC. Conclusions The present study retrieved from large real–world data suggested that response to primary systemic therapy and aggressive radiotherapy are independent prognostic factors for SCLC. PCI and initiative irradiation for original or metastatic sites improved the OS in LS‐SCLC and ES‐SCLC, respectively., The present study of real‐world data from 988 patients suggested that elevating primary systemic therapy response rate and aggressive radiotherapy are independent prognostic factors for SCLC. PCI and initiative irradiation for original or metastatic sites improved the OS in LS‐SCLC and ES‐SCLC, respectively.

The liver is a vital organ that controls glucose and lipid metabolism, hormone regulation, and bile secretion. Liver injury can occur from various insults such as viruses, metabolic diseases, and alcohol, which lead to acute and chronic liver diseases. Recent studies have demonstrated the implications of long non-coding RNAs (lncRNAs) in the pathogenesis of liver diseases. These newly discovered lncRNAs have various functions attributing to many cellular biological processes via distinct and diverse mechanisms. LncRNA H19, one of the first lncRNAs being identified, is highly expressed in fetal liver but not in adult normal liver. Its expression, however, is increased in liver diseases with various etiologies. In this review, we focused on the roles of H19 in the pathogenesis of liver diseases. This comprehensive review is aimed to provide useful perspectives and translational applications of H19 as a potential therapeutic target of liver diseases.

Broadband transmitted wavefront measurement is a detection method that uses transmitted wavefronts at a few specific wavelengths though a function of Zernike coefficients and wavelength to predict other transmitted wavefronts at any wavelength within a certain range. This method is used when the designed wavelength of the interferometer and the detection wavelength are different. The function of the Zernike coefficients and wavelength can be expressed by the Conrady formula which can be used to describe a monotonic function curve or a function curve with an inflection point. Two methods, i.e., solving and fitting, can be used to determine the coefficients of the Conrady formula. Owing to the inevitable errors in the actual measurements, the fitting method is preferred to determine the coefficients of the Conrady formula. However, by analyzing the Conrady formula, it was found that the curve obtained by fitting the Conrady formula is a monotonic curve. This method cannot be used to obtain a curve with an inflection point or a slow-changing curve in the long waveband. In this paper, we propose an improved data fitting approach that transforms the Conrady formula into a polynomial formula to fit a given set of data for determining the Conrady formula coefficients. The correctness of the method was verified via simulations. Finally, the feasibility of the proposed method was verified by changing the light source and using the Fizeau interferometer to measure the transmitted wavefront of the doublet lens. To ascertain the feasibility of using visible light to predict the invisible light band, a near-infrared 1064 nm light source was added to the experimental set-up to broaden the range of the transmitted wavefront prediction waveband. Experimental results showed that the conversion polynomial fitting method can be used to obtain monotonic curves and the curve with an inflection point and a slow-changing curve in the long waveband, thereby mitigating the limitation of directly fitting the Conrady formula using a set of data points. Furthermore, using this method, we verified that the visible light can be used to predict the transmitted wavefront at any wavelength in the invisible light band. This observation is highly significant for the practical applications of the broadband transmitted wavefront measurement technique.

Aims Alcohol-associated liver disease represents a spectrum of histopathological changes from steatosis to advanced fibrosis and cirrhosis. The major goals of this retrospective study were to characterize the histologic features in patients with excessive alcohol use who presented with an abnormal hepatic panel and/or abnormal radiographic imaging and did not meet the clinical diagnosis of alcoholic hepatitis or cirrhosis. Methods We performed a retrospective study to describe hepatic histology of 62 and 83 excessive drinkers with normal and abnormal serum aspartate transaminase, respectively. The types of inflammatory cells in the liver were characterized by immunohistochemistry for CD4, CD8, CD20, CD68 and myeloperoxidase. Results Among 62 patients with aspartate aminotransferase (AST) ≤ 50 U/L, 37% had histological evidence of steatosis. Of these, we found evidence of hepatocyte ballooning (21%), lobular inflammation (50%), portal inflammation (52%) and fibrosis (14%). For those with AST > 50 U/L, the presence of hepatic steatosis, lobular inflammation and portal inflammation was observed in 29, 60 and 69% of patients, respectively. Fibrosis was found in 33%, four with bridging fibrosis, and one with cirrhosis. We observed the aggregation of CD68+ macrophages, rather than normally distributed with minimal neutrophilic infiltration. Lobular and portal lymphocytic infiltrations are primarily CD8+ T cells. Conclusion Abnormal hepatic histopathology occurs in excessive drinkers with normal transaminase activity. Future studies to determine the diagnostic modalities to detect such abnormalities and to better understand its clinical implications and long-term outcome are needed.

The sound absorption coefficient was evaluated for the acoustic performance of the pavement in many studies, which is an evaluation index generated by the non-contact interaction between the tyre a...

Lung cancer is one of the malignant tumors with high incidence rate and high mortality worldwide. Telomere and telomerase are closely related to the occurrence and development of lung cancer. Although telomerase may not be the direct cause of carcinogenesis, it plays a key role in maintaining telomere length and tumor growth. The length of most tumors, including lung cancer, is shortened. The change of telomere length is related to the risk of lung cancer, and may become the therapeutic target and predictive index. Target drugs for telomere and telomerase signaling pathway are constantly being explored, and drugs represented by telomerase inhibitors are expected to be used in clinical treatment of lung cancer in the future. However, the research on telomere and telomerase is far from enough. The bypass mechanism of telomere length maintenance may be the direction of further research.

Oxidative stress is considered a possible mechanism of irritable bowel syndrome (IBS) and depression. This study determined the possible association of serum peroxiredoxin 1 (PRDX1; a key antioxidant enzyme) and brain-derived neurotrophic factor (BDNF) with anxiety and depression symptoms in IBS patients.According to the Rome IV diagnostic criteria, 177 IBS patients from February 2019 to July 2019 were included. Serum levels of PRDX1, BDNF, and TNFα were detected by enzyme-linked immunosorbent assay. Levels of anxiety and depression were assessed with the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS).Compared with normal IBS patients, patients with anxiety and depression symptoms had significantly higher serum PRDX1 (p0.001; p=0.002) and TNFα (p0.001; p = 0.002) and significantly lower BDNF (p 0.001; p = 0.002). Serum PRDX1 (r = 0.659, p 0.001; r = 0.466, p 0.001) and TNFα (r = 0.531, p 0.001; r = 0.449, p 0.001) were positively correlated with SAS and SDS, respectively, whereas BDNF was negatively correlated with SAS (r = 0.594, p 0.001) and SDS (r = 0.534, p 0.001). Multivariable regression analysis revealed that IBS severity, BDNF, and PRDX1 were significant predictors of anxiety. BDNF was also a significant predictor of depression.Elevated PRDX1 and decreased BDNF in serum may be closely related to psychological symptoms in IBS. Results of this study suggested that PRDX1 may be an important target for IBS treatment in fighting against intestinal and psychological symptoms.

Broadband transmitted wavefront measurement is a detection method that uses transmitted wavefronts at a few specific wavelengths though a function of Zernike coefficients and wavelength to predict other transmitted wavefronts at any wavelength within a certain range. This method is used when the designed wavelength of the interferometer and the detection wavelength are different. The function of the Zernike coefficients and wavelength can be expressed by the Conrady formula which can be used to describe a monotonic function curve or a function curve with an inflection point. Two methods, i.e., solving and fitting, can be used to determine the coefficients of the Conrady formula. Owing to the inevitable errors in the actual measurements, the fitting method is preferred to determine the coefficients of the Conrady formula. However, by analyzing the Conrady formula, it was found that the curve obtained by fitting the Conrady formula is a monotonic curve. This method cannot be used to obtain a curve with an inflection point or a slow-changing curve in the long waveband. In this paper, we propose an improved data fitting approach that transforms the Conrady formula into a polynomial formula to fit a given set of data for determining the Conrady formula coefficients. The correctness of the method was verified via simulations. Finally, the feasibility of the proposed method was verified by changing the light source and using the Fizeau interferometer to measure the transmitted wavefront of the doublet lens. To ascertain the feasibility of using visible light to predict the invisible light band, a near-infrared 1064 nm light source was added to the experimental set-up to broaden the range of the transmitted wavefront prediction waveband. Experimental results showed that the conversion polynomial fitting method can be used to obtain monotonic curves and the curve with an inflection point and a slow-changing curve in the long waveband, thereby mitigating the limitation of directly fitting the Conrady formula using a set of data points. Furthermore, using this method, we verified that the visible light can be used to predict the transmitted wavefront at any wavelength in the invisible light band. This observation is highly significant for the practical applications of the broadband transmitted wavefront measurement technique.

Aiming at the problem that it is difficult to achieve accurate laying of model and precise excavation of roadways in special surrounding rock structure roadway according to conventional physical similarity simulation, which reduces the reliability of experimental results. An accurate laying of model and precise excavation of roadway method, named “labeling positioning and drawing line, presetting roadway model” (LPDLPRM), was proposed. The physical similarity simulation of deformation and failure characteristics of surrounding rock of coal-rock rise, under the influence of repeated mining in close distance coal seams, was carried out based on the method and infrared detection. The results show that the coal-rock rise in close distance coal seams was affected by repeated mining disturbances, and the surrounding rock of coal-rock rise was characterized by obvious asymmetric deformation, specific for the stress and strain near the coal pillar were higher than that of other parts, and cracks near the coal pillar were denser than other parts; when the coal seam is mined in which the coal-rock rise is located, the stress concentration of the surrounding rock near the rise was weakened by mining pressure relief in the upper coal seam; the stress concentration of the surrounding rock near the rise increases when the coal and the lower coal seam are mined, and the stress on the right side (coal pillar side) near the coal-rock rise was the most concentrated. Therefore, it is important to take measures to strengthen support near the coal pillar and to control asymmetric deformation when the coal-rock rise is influenced by repeated mining.

In order to reveal the influence of the pull-out rate on the load-bearing properties of the coal–rock combined anchor body, the mechanical properties and failure characteristics of a coal–rock combined anchor body under different pull-out rates (10, 20, 30, 40, 50 mm/min) were studied using the pull-out test and theoretical analysis. The results show that the bearing capacity of the bolt on the coal–rock combined anchor body improves under a dynamic load, but the load-bearing properties of the coal–rock combined anchor body are different from those of the full rock (coal) anchor body. With the increase in the pull-out rate, the maximum pull-out load of the bolt on the coal–rock combined anchor body increases first, then decreases, and finally tends to be stable. Under the condition of a low drawing rate, the bearing capacity of the coal–rock combined anchor system can be greatly improved, but when the pull-out rate exceeds 20 mm/min, the bearing capacity of the anchor system is reduced. The debonding process of the anchoring section of the coal–rock combined anchor body gradually expands from the beginning section of the anchor to the bottom of the borehole. The coal–rock combined anchor body undergoes time differential development of cracks, and the failure of the coal and rock mass occurs at different times. Its failure process can be divided into three stages: (1) the coal anchor and rock anchor act together; (2) the rock anchor acts alone; and (3) the coal anchor and rock anchor have residual action.

Aggregate geometrical features directly affect asphalt pavement surface properties, which further affect the resistance to skidding of a road surface. In order to establish a relationship between the aggregate geometrical features and pavement surface properties, this paper employs an aggregate geometric characteristic evaluation system (AGCES) to describe the form property, angularity, and surface texture of aggregate particles. The geometrical feature parameters of 15 different aggregates were examined by AGCES and the corresponding surface properties of asphalt pavement prepared from the mentioned aggregates were evaluated by sand patch method, 2-Dimension Image-based Texture Analysis Method (2D-ITAM) and Walking Friction Tester (WFT), respectively. The relationships between the pavement surface property parameters and the aggregate geometric characteristic parameters studied were developed by the Levenberg-Marquarat and universal global optimization (LM-UGO). The results show that the calculated geometric characteristic parameters are in agreement with traditional manual measurement results. The pavement surface properties are significantly influenced by aggregate angularity and aggregate surface texture. Regression relationships were established to predict pavement surface properties from the aggregate geometrical features.

Surrounding rock deformation control of gob-side coal-rock roadway in inclined coal seams (GCRICS) is a major problem in gob-side entry technology application practice. This paper describes a case study of the surrounding rock deformation characteristics and control technology of a typical GCRICS in Guizhou, China. As according to data obtained during a field investigation, the reasons for the deformation and failure of 151509 tailentry and the shortcomings of the original support scheme were analyzed. In combination with existing theory and field experience, the “anchor cable + U-shaped steel + shotcreting + grouting” (CUSG) support method was proposed. The plastic zone distribution, displacement, and stress evolution law of the roadway-surrounding rock under the four support modes were analyzed and compared by numerical simulation. The results show that the supporting effects of several support methods varied from good to poor; CUSG was the best, followed by anchor cable support, U-shaped steel support, and then no support. Based on the previous seepage grouting theory, a slurry diffusion model of hollow grouted anchor cable (HGC) was established and the calculation formulas of slurry diffusion radius and grouting time were deduced, which provided guidance for field construction. Finally, the CUSG surrounding rock control technology was applied to 151509 tailentry subsequent roadway support. Through drill holes, analysis of the surrounding rock of the non-grouting area and the grouting area was conducted. It was found that the surrounding rock of the grouting area was high in integrity and strong in bearing capacity. Throughout the excavation period to the end of roadway mining, the roadway did not have to be repaired. This case study has high practicability, high popularization value, and provides a useful reference for the engineering support design of the GCRICS.

Savolitinib, a selective MET inhibitor, showed efficacy in patients with non-small cell lung cancer (NSCLC), including pulmonary sarcomatoid carcinoma (PSC), harbouringTo analyseA multicentre, single-arm, open-label phase 2 study.All enrolled patients with baseline plasma samples were included. Outcomes were objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) by baselineAmong 66 patients with baseline ctDNA sequencing, 46 (70%) had detectablectDNA biomarkers may allow for longitudinal monitoring of clinical outcomes with savolitinib in patients withThe trial was registered with ClinicalTrials.gov (NCT02897479) on 13 September 2016.

In the actual working condition, the cavitation phenomenon is inevitably accompanied by the collapse of a large number of bubbles, and will affect the performance of hydraulic machinery. Therefore, it is of great significance to study the process of multi-bubble collapse. The double bubble system is the most simplified one in multi-bubble system, and it is also the basis of studying multi-bubble. However, the existing bubble dynamic studies mainly focused on single bubble and its interaction with the wall. This paper studies the interaction between two bubbles with different sizes and the influence of the wall on the process of bubble collapse by the VOF method. We have already investigated the interaction between two bubbles with different sizes without a wall (in free water) in our previous study. In this paper, we find that if there is a wall nearby, these two bubbles move close to each other when collapsing, and both move close to the wall at the same time. Through the study of bubble collapse time in the single bubble and the double bubble system, we find that the existence of the wall will delay the collapse time of bubble. However, the existence of the wall can also increase the intensity of collapse and rebound process of the bubble. Through the study of the center displacement of the bubble, we find that the double bubble system can increase the displacement of both bubbles. The method used in this paper can be easily extended to the study of multi-bubble, which provides a feasible method for the simulation of multi-bubble collapse near the wall.

MicroRNA-7 (miR-7) is a small non-coding RNA, which plays critical roles in regulating gene expression of multiple key cellular processes. MiR-7 exhibits a tissue-specific pattern of expression, with abundant levels found in the brain, spleen, and pancreas. Although it is expressed at lower levels in other tissues, including the liver, miR-7 is involved in both the development of organs and biological functions of cells. In this review, we focus on the mechanisms by which miR-7 controls cell growth, proliferation, invasion, metastasis, metabolism, and inflammation. We also summarize the specific roles of miR-7 in liver diseases. MiR-7 is considered as a tumor suppressor miRNA in hepatocellular carcinoma and is involved in the pathogenesis of hepatic steatosis and hepatitis. Future studies to further define miR-7 functions and its mechanism in association with other types of liver diseases should be explored. An improved understanding from these studies will provide us a useful perspective leading to mechanism-based intervention by targeting miR-7 for the treatment of liver diseases.

Long non-coding RNAs (lncRNAs), a class of transcribed RNA molecules with the lengths exceeding 200 nucleotides, are not translated into protein. They can modulate protein-coding genes by controlling transcriptional and posttranscriptional processes. The dysregulation of lncRNAs has been related to various pathological disorders. In this review, we summarized the current knowledge of lncRNAs and their implications in the pathogenesis of three common liver diseases: nonalcoholic fatty liver disease, alcohol-related liver disease, and cholestatic liver disease. Future studies to further define the role of lncRNAs and their mechanisms in various types of liver diseases should be explored. An improved understanding from these studies will provide us a useful perspective leading to mechanism-based intervention by targeting specific lncRNAs for the treatment of liver diseases.