Search

Abstract Background Although the inherited risk factors associated with fatty liver disease are well understood, little is known about the genetic background of metabolic dysfunction-associated steatotic liver disease (MASLD) and its related health impacts. Compared to non-alcoholic fatty liver disease (NAFLD), MASLD presents significantly distinct diagnostic criteria, and epidemiological and clinical features, but the related genetic variants are yet to be investigated. Therefore, we conducted this study to assess the genetic background of MASLD and interactions between MASLD-related genetic variants and metabolism-related outcomes. Methods Participants from the UK Biobank were grouped into discovery and replication cohorts for an MASLD genome-wide association study (GWAS), and base and target cohorts for polygenic risk score (PRS) analysis. Autosomal genetic variants associated with NAFLD were compared with the MASLD GWAS results. Kaplan–Meier and Cox regression analyses were used to assess associations between MASLD and metabolism-related outcomes. Results Sixteen single-nucleotide polymorphisms (SNPs) were identified at genome-wide significance levels for MASLD and duplicated in the replication cohort. Differences were found after comparing these SNPs with the results of NAFLD-related genetic variants. MASLD cases with high PRS had a multivariate-adjusted hazard ratio of 3.15 (95% confidence interval, 2.54–3.90) for severe liver disease (SLD), and 2.81 (2.60–3.03) for type 2 diabetes mellitus. The high PRS amplified the impact of MASLD on SLD and extrahepatic outcomes. Conclusions High PRS of MASLD GWAS amplified the impact of MASLD on SLD and metabolism-related outcomes, thereby refining the process of identification of individuals at high risk of MASLD. Supplementation of this process with relevant genetic backgrounds may lead to more effective MASLD prevention and management.

Abstract Hyperuricemia (HUA) has emerged as the second most prevalent metabolic disorder characterized by prolonged and asymptomatic period, triggering gout and metabolism‐related outcomes. Early detection and prognosis prediction for HUA and gout are crucial for pre‐emptive interventions. Integrating genetic and clinical data from 421287 UK Biobank and 8900 Nanfang Hospital participants, a stacked multimodal machine learning model is developed and validated to synthesize its probabilities as an in‐silico quantitative marker for hyperuricemia (ISHUA). The model demonstrates satisfactory performance in detecting HUA, exhibiting area under the curves (AUCs) of 0.859, 0.836, and 0.779 within the train, internal, and external test sets, respectively. ISHUA is significantly associated with gout and metabolism‐related outcomes, effectively classifying individuals into low‐ and high‐risk groups for gout in the train (AUC, 0.815) and internal test (AUC, 0.814) sets. The high‐risk group shows increased susceptibility to metabolism‐related outcomes, and participants with intermediate or favorable lifestyle profiles have hazard ratios of 0.75 and 0.53 for gout compared with those with unfavorable lifestyles. Similar trends are observed for other metabolism‐related outcomes. The multimodal machine learning‐based ISHUA marker enables personalized risk stratification for gout and metabolism‐related outcomes, and it is unveiled that lifestyle changes can ameliorate these outcomes within high‐risk group, providing guidance for preventive interventions.

Background and Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) poses a considerable health risk. Nevertheless, its risk factors are not thoroughly comprehended, and the association between the reticulocyte count and MASLD remains uncertain. This study aimed to explore the relationship between reticulocyte count and MASLD.Methods: A total of 310,091 individuals from the UK Biobank were included in this cross-sectional study, and 7,316 individuals were included in this prospective study. The cross-sectional analysis categorized reticulocyte count into quartiles, considering the sample distribution. Logistic regression models examined the connection between reticulocyte count and MASLD. In the prospective analysis, Cox analysis was utilized to investigate the association.Results: Our study findings indicate a significant association between higher reticulocyte count and an elevated risk of MASLD in both the cross-sectional and prospective analyses. In the cross-sectional analysis, the adjusted odds ratios (ORs) of MASLD increased stepwise over reticulocyte count quartiles (quartile 2: OR 1.22, 95% CI 1.17–1.28, p < 0.001; quartile 3: OR 1.44; 95% CI 1.38–1.51, p < 0.001; quartile 4: OR 1.66, 95% CI 1.59–1.74, p < 0.001). The results of prospective analyses were similar.Conclusion: Increased reticulocyte count was independently associated with a higher risk of MASLD. This discovery offers new insights into the potential of reticulocytes as biomarkers for MASLD.

The pre-stressed flexible cable-supported photovoltaic (PV) systems (FCSPSs) are gradually becoming the preferred PV structure for large-span and mountain photovoltaic power plants. The wind-induced response of FCSPSs under negative wind conditions is more pronounced than under positive wind conditions. In this study, a series of two-way fluid-structure interaction (FSI) coupling numerical simulations are conducted to investigate the effect of ground anchors on the wind-induced vibration response of FCSPSs. Firstly, an analysis approach for wind-induced vibration coefficients of FCSPSs is established, involving model equivalency, coefficient definitions, model creation, and grid and solution settings. Secondly, modal analysis is performed on FCSPSs by varying the stiffness ratio (SR) of the ground anchor. Subsequently, changes in support reaction, ground anchor tension, translational displacement, and rotational displacement, as well as the wind field variation in the fluid domain under wind load, are evaluated for SR values ranging from 0 to 5. Finally, a quantitative evaluation of the wind-induced vibration coefficient in the FCSPS is conducted for different SR values. The results indicate that the configuration of ground anchor cables significantly mitigates the support reaction and displacement response of the FCSPS under negative wind conditions. Moreover, the stiffness ratio of the ground anchor has a relatively minor impact on wind-induced vibration coefficients (reaction force, displacement).

Abstract Background Artificial intelligence (AI)-assisted clinical trial screening is a promising prospect, although previous matching systems were developed in English, and relevant studies have only been conducted in Western countries. Therefore, we evaluated an AI-based clinical trial matching system (CTMS) that extracts medical data from the electronic health record system and matches them to clinical trials automatically. Methods This study included 1,053 consecutive inpatients primarily diagnosed with hepatocellular carcinoma who were referred to the liver tumor center of an academic medical center in China between January and December 2019. The eligibility criteria extracted from two clinical trials, patient attributes, and gold standard were decided manually. We evaluated the performance of the CTMS against the established gold standard by measuring the accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and run time required. Results The manual reviewers demonstrated acceptable interrater reliability (Cohen’s kappa 0.65–0.88). The performance results for the CTMS were as follows: accuracy, 92.9–98.0%; sensitivity, 51.9–83.5%; specificity, 99.0–99.1%; PPV, 75.7–85.1%; and NPV, 97.4–98.9%. The time required for eligibility determination by the CTMS and manual reviewers was 2 and 150 h, respectively. Conclusions We found that the CTMS is particularly reliable in excluding ineligible patients in a significantly reduced amount of time. The CTMS excluded ineligible patients for clinical trials with good performance, reducing 98.7% of the work time. Thus, such AI-based systems with natural language processing and machine learning have potential utility in Chinese clinical trials.

Objective To establish a model that can predict the occurrence of acute kidney disease (AKD) in liver cirrhotic patients and evaluate its performance. Methods Liver cirrhotic patients who hospitalized in the department of gastroenterology of the First Hospital of Lanzhou University from January 2017 to January 2022 were retrospectively included. They were divided into AKD and non-AKD groups according to whether they were combined with AKD during hospitalization, and were randomized into training and validation sets in a 7∶3 ratio. The clinical data of patients in the two groups were collected, and LASSO regression and multifactorial Logistic regression were used to screen the influencing factors for the occurrence of AKD in patients with liver cirrhosis and to establish a prediction model. The model was then evaluated by using the receiver operating characteristic curve, the calibration curve and the clinical decision curve. Results A total of 796 cases of liver cirrhotic patients who met the inclusion and exclusion criteria were enrolled. Among them, 103 cases were in the AKD group and 693 cases were in the non-AKD group; 561 cases were in the training set and 235 cases were in the validation set. The results of LASSO regression and multifactorial Logistic regression showed that a history of diabetes (OR=2.922, 95% CI: 1.290-6.564, P=0.009), hepatic encephalopathy (OR=6.210, 95% CI: 2.278-17.479, P < 0.001), gastrointestinal bleeding (OR=2.501, 95% CI: 1.236-5.073, P=0.011), ascites (OR=3.219, 95% CI: 1.664-6.539, P < 0.001), male (OR=0.477, 95% CI: 0.254-0.879, P=0.019), hemoglobin (OR=0.987, 95% CI: 0.975-0.999, P=0.044), albumin (OR=0.952, 95% CI: 0.911-0.991, P=0.023), and prothrombin time (OR=0.865, 95% CI: 0.779-0.920, P < 0.001) were the independent influences on the occurrence of AKD in liver cirrhotic patients, and were used to construct a prediction model. The area under the curve of the model in the training set and validation set for predicting the occurrence of AKD in liver cirrhotic patients was 0.895 (95% CI: 0.865-0.925) and 0.869 (95% CI: 0.807-0.930), respectively. The calibration curves showed that the model had good fit and consistency and the clinical decision curves showed that the use of the model for predicting the risk of AKD could benefit liver cirrhotic patients overall. Conclusions A prediction model for the occurrence of AKD in liver cirrhotic patients was established based on eight influencing factors, including gender, history of diabetes, and hepatic encephalopathy. It was validated to have good discrimination, calibration, and clinical utility, and is expected to assist in the clinical early screening and identification of liver cirrhosis-associated AKD.

Abstract Immune checkpoint inhibitors (ICIs) are safe and efficacious treatments for advanced primary liver cancer (PLC). The efficacy of different ICIs in the treatment of liver cancer remains unclear. The purpose of this study was to explore whether there is a difference in the efficacy and safety of various programmed cell death protein 1 (PD-1) inhibitors in combination with lenvatinib in the treatment of unresectable PLC. Patients with PLC treated with lenvatinib in combination with PD-1 inhibitors (camrelizumab, tislelizumab, sintilimab, or pembrolizumab) between January 2018 and December 2021 were retrospectively enrolled. Tumor response, adverse events, and grades were evaluated. Kaplan–Meier analysis and log-rank test were used to compare the overall survival and progression-free survival of patients treated with different PD-1 inhibitors. Cox regression analysis was used for univariate and multivariate analyses to identify clinical variables related to treatment efficacy. This study included a total of 176 patients who received a combination of lenvatinib and PD-1 inhibitors. Of these, 103 patients received camrelizumab, 44 received tislelizumab, 20 received sintilimab, and 9 received pembrolizumab. There was no significant difference in the pairwise comparison of camrelizumab, tislelizumab, sintilimab, and pembrolizumab using Kaplan–Meier survival analysis. Adverse events occurred in 40 (22.7%) patients (grade ≥ 3, 2.3%). The incidence of grade 3 adverse events among the four PD-1 inhibitor groups was below 5%. Camrelizumab, tislelizumab, sintilimab, and pembrolizumab are viable options for patients with unresectable PLC. These PD-1 inhibitors in combination with lenvatinib showed good safety profiles. The results guide selecting treatment for patients with unresectable PLC.

In recent years, Shale gas has been the fastest-growing energy source in the world. In USA, shale gas now contributes to more than 60 % of natural gas supply. In China, annual shale gas production climbed to 800 Bcf (billion cubic feet) in 2021. However, drilling in shale has been a major challenge since the dawn of petroleum industry due to the reactive clay minerals.This paper surveys the field cases of drilling fluids in major shale plays. OBM (oil based mud), formulated with diesel and low fraction of water phase, provides effective shale stability, excellent lubricity, and high rate of penetration (ROP). As a result, more than 70 % of shale gas wells have been drilled with OBM with very few reported cases of wellbore instability. WBM (water-based mud) is made of water and necessary chemical additives. WBM is less costly and more environment-friendly than OBM, however some shale wells drilled with WBM reported severe instability issues. Nevertheless, recent innovations in WBM lead to successes in drilling major shale plays. WBM has great potential in shale drilling and deserves more research and improvements.

The ability of humans to discern facial expressions in a timely manner typically relies on distributed face-selective regions for rapid neural computations. To study the time course in regions of interest for this process, we used magnetoencephalography (MEG) to measure neural responses participants viewed facial expressions depicting seven types of emotions (happiness, sadness, anger, disgust, fear, surprise, and neutral). Analysis of the time-resolved decoding of neural responses in face-selective sources within the inferior parietal cortex (IP-faces), lateral occipital cortex (LO-faces), fusiform gyrus (FG-faces), and posterior superior temporal sulcus (pSTS-faces) revealed that facial expressions were successfully classified starting from ∼100 to 150 ms after stimulus onset. Interestingly, the LO-faces and IP-faces showed greater accuracy than FG-faces and pSTS-faces. To examine the nature of the information processed in these face-selective regions, we entered with facial expression stimuli into a convolutional neural network (CNN) to perform similarity analyses against human neural responses. The results showed that neural responses in the LO-faces and IP-faces, starting ∼100 ms after the stimuli, were more strongly correlated with deep representations of emotional categories than with image level information from the input images. Additionally, we observed a relationship between the behavioral performance and the neural responses in the LO-faces and IP-faces, but not in the FG-faces and lpSTS-faces. Together, these results provided a comprehensive picture of the time course and nature of information involved in facial expression discrimination across multiple face-selective regions, which advances our understanding of how the human brain processes facial expressions.

We combined multivariate pattern analysis (MVPA) and electroencephalogram (EEG) to investigate the role of edge, color, and other surface information in the neural representation of visual objects. Participants completed a one-back task in which they were presented with color photographs, grayscale images, and line drawings of animals, tools, and fruits. Our results provide the first neural evidence that line drawings elicit similar neural activities as color photographs and grayscale images during the 175–305 ms window after the stimulus onset. Furthermore, we found that other surface information, rather than color information, facilitates decoding accuracy in the early stages of object representations and affects the speed of this. These results provide new insights into the role of edge-based and surface-based information in the dynamic process of neural representations of visual objects.

Microecology has been shown to be closely related to digestive diseases, and most of the research on gastric microecology has focused on Helicobacter pylori. With the development of microarray and gene detection technology, in addition to Helicobacter pylori, more and more bacteria genera have been discovered, such as Actinomyces, Firmicute and Clostridium. These bacteria genera and their abundance changes have also been proved to be closely related to the occurrence and development of gastric cancer. In this paper, the role and possible mechanism of gastric microecology in the occurrence and development of gastric cancer are reviewed, with the hope of providing reference for clinical diagnosis and treatment.

Objective To investigate the characteristics of changes in serum degraded monosaccharide levels in children with systemic lupus erythematosus (SLE) and its relationship with the severity of the disease and immune dysfunction. Methods Children firstly diagnosed as SLE and hospitalized in the Affiliated Hospital of Qingdao University from January 2019 to March 2022 were enrolled in the SLE group, healthy childrenwho underwent physical examination at the same period were chosen as the control and matched in a ration of 1∶1 in age and sex with the SLE group. The clinical data of both groups were collected. The serum levels of five kinds of degraded monosaccharides, which were mannose, glucosamine, aminogalactose, N-acetyl glucosamine and galactose, were analyzed in both groups. The correlations between serum levels of degraded monosaccharides and SLE disease activity and immunologic markers were analyzed with Pearson correlation coefficient. Results Totally 45 children with SLE (13 with mild disease activity, 15 with moderate disease activity, and 17 with severe disease activity) and 50 healthy children were enrolled in the experiment. Compared with the control group, the SLE group showed elevated levels of serum mannose, glucosamine, aminogalactose, N-acetyl glucosamine, and galactose (all P < 0.05); and serum levels of mannose, N-acetyl glucosamine, and galactose gradually increased with increasing disease activity (all P < 0.05). There was no significant difference in glucosamine and aminogalactose levels in children with SLE of different disease activity (all P > 0.05). Pearson correlation coefficient showed that serum degraded monosaccharide levels were positively correlated with disease activity indexes and various immunologic markers. Conclusions Serum levels of degraded monosaccharides in children with SLE are elevated and some of which are correlated with disease activity and immune dysfunction.

This study examined whether three subtypes of anxiety (trait anxiety, state anxiety, and social anxiety) have different effects on recognition of facial expressions. One hundred and thirty-eight participants matched facial expressions of three intensity levels (20 %, 40 %, 100 %) with one of the six emotion labels (“happy”, “sad”, “fear”, “angry”, “disgust”, and “surprise”). While using a conventional method of analysis we were able to replicate some significant correlations between each anxiety type and recognition performance found in the literature. However, when we used partial correlation to isolate the effect of each anxiety type, most of these correlations were no longer significant, apart from the negative correlations between Beck Anxiety Inventory and reaction time to fearful faces displayed at 40 % intensity level, and the correlations between anxiety and categorisation errors. Specifically, social anxiety was positively correlated with misidentifying a happy face as a disgust face at 40 % intensity level, and state anxiety negatively correlated with misidentifying a happy face as a sad face at 20 % intensity level. However, these partial correlation analyses became non-significant after p value adjustment for multiple comparisons. Our eye tracking data also showed that state anxiety may be associated with reduced fixations on the eye regions of low-intensity sad or fearful faces. These analyses cast doubts on some effects reported in the previous studies because they are likely to reflect a mixture of influences from highly correlated anxiety subtypes.

ObjectiveTo evaluate the accuracy of using the vergence formula to screen myopia in children and adolescents.MethodsThis was a cross-sectional study conducted between December 2022 and May 2023 at the ophthalmology clinic of Beijing Tongren Hospital. A total of 336 children aged 6 to 12 years with refractive errors were selected according to the inclusion criteria. Biometric measurements, including axial length, corneal thickness, anterior chamber depth, corneal curvature, and lens thickness, were obtained using a biometer. The Calculated spherical equivalent (SE) was then calculated using the vergence formula. Cycloplegic refraction was performed after paralysis of the ciliary muscle, and the subjective SE was recorded. A diagnosis of myopia was made if the subjective SE was ≤ −0.50 diopters.ResultsThe AL/CR, subjective SE, and calculated SE were not normally distributed (p

In order to meet the needs of target detection in shallow water with concealed and low energy consumption platform, the Bayesian estimation theory was applied to underwater acoustic location. The underwater acoustic location model was established based on probability density function as the description of sound source state, so as to overcome the problems of unstable shallow water environment and mismatching of sound field model. Histogram filtering method is used to solve the integral solution in the process of posterior probability estimation of sound source state. The hierarchical grid histogram filtering method is proposed for the first time, which effectively improves the efficiency of histogram filtering iterative algorithm. The measured data and simulation results of SWelleX-96 show that the depth positioning accuracy can reach 35 m and the distance positioning accuracy can reach 0.69 km within the range of 200 m deep and 10 km long in shallow water environment, and the efficiency of the algorithm can be improved by N1/2 times.

Abstract Background & aims Immune checkpoint inhibitors (ICIs) play an increasingly important role in the treatment of primary liver cancer (PLC). Some patients with PLC experience symptoms of splenomegaly. Splenomegaly may affect the efficacy of ICIs due to an imbalance of the immune microenvironment. Currently, there is a lack of evidence on the relationship between splenomegaly and prognosis in patients with PLC treated with ICIs. This study analyzed the relationship between splenomegaly and prognosis in patients with PLC treated with ICIs. Methods In this retrospective cohort study of 161 patients with PLC treated with ICIs, splenomegaly was diagnosed using computed tomography or magnetic resonance imaging and the impact of splenomegaly on patient survival was analyzed. Results Through univariate and multivariate Cox regression analyses, we determined that splenomegaly was associated with shortened overall survival (p = 0.002) and progression‐free survival (p = 0.013) in patients with PLC treated with ICIs. Kaplan–Meier analysis further validated our results. The overall survival and progression‐free survival of patients with splenomegaly were significantly shorter than those of patients without splenomegaly (p

Abstract Myosin 1b (Myo1b) is an important single-headed membrane-associated motor of class I myosins that participate in many critical physiological and pathological processes. Mounting evidence suggests that the dysregulation of Myo1b expression has been extensively investigated in the development and progression of several tumors. However, the functional mechanism of Myo1b in CRC angiogenesis and autophagy progression remains unclear. Herein, we found that the expression of Myo1b was upregulated in CRC tissues and its high expression was correlated with worse survival. The overexpression of Myo1b promoted the proliferation, migration and invasion of CRC cells. Conversely, silencing of Myo1b suppressed tumor progression both in vitro and in vivo. Further studies indicated that Myo1b inhibited the autophagosome-lysosome fusion and potentiated the VEGF secretion of CRC cells to promote angiogenesis. Mechanistically, Myo1b blocked the autophagic degradation of HIF-1α and then led to the accumulation of HIF-1α, thus enhancing VEGF secretion and then promoting tumor angiogenesis in CRC. Together, our study provided novel insights into the role of Myo1b in CRC progression and revealed that it might be a feasible predictive biomarker and promising therapeutic target for CRC patients.

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common and malignant tumors in the digestive tract. Tumor Suppressor Candidate 3 (TUSC3) is one subunit of the endoplasmic reticulum Oligosaccharyl transferase (OST) complex, which plays an important role in N-glycosylation during the protein folding process. However, the role of TUSC3 in the initiation and progression of HCC has not been mentioned yet. In the present study, we aim to investigate the effects of TUSC3 on the initiation and progression of HCC. Methods Immunohistochemical assay and qRT-PCR were used to detect the expression of TUSC3 and lipase C hepatic type (LIPC) in HCC tissue and cells. Loss-of-function and gain-of-function were applied to detect the function of TUSC3 and LIPC in vivo and in vitro. Immunofluorescence assay and co-immunoprecipitation were used to detect the relationship between TUSC3 and LPC. Western blot was applied to detect the expression of epithelial–mesenchymal transition (EMT) markers and the Akt signaling pathway. Results TUSC3 was aberrantly decreased in hepatocellular carcinoma tissues compared to the matched adjacent normal tissues, which resulted in bigger size of tumor (P = 0.001, Table 2), worse differentiation (P = 0.006, Table 2) and an advanced BCLC stage. Down-regulation of TUSC3 led to the enhanced proliferation and migration of hepatocellular carcinoma cells in vivo and vitro, whereas the opposite effect could be observed in the TUSC3-overexpression group. The analysis of TUSC3 microarray showed that LIPC, a glycoprotein primarily synthesized and secreted by hepatocytes, was a downstream target of TUSC3, and it negatively modulated the development of HCC. The morphological changes in HCC cells indicated that TUSC3 regulated the epithelial-mesenchymal transition (EMT). Mechanistically, TUSC3 inhibited EMT progression through the LIPC/AKT axis. Conclusion Down-regulation of TUSC3 promotes EMT progression by activating AKT signaling via targeting LIPC in HCC, which is probably the possible mechanism driving TUSC3-deficient hepatocellular carcinoma cells toward a malignant phenotype.

Background and aim: Immune checkpoint inhibitors (ICIs) are widely used in the treatment of liver cancer. However, the interaction with other drugs may change the efficacy of ICIs. Few studies investigated the effects of antibiotics (ATBs) on the efficacy of immunotherapy and the survival of patients with primary liver cancer receiving immunotherapy. This study aimed to explore the impact of ATBs on the efficacy of immunotherapy in patients with primary liver cancer. Methods: In total, 215 patients with primary liver cancer who received ICIs from June 2018 to October 2020 were included for retrospective analysis. The progression-free survival (PFS), disease control rate (DCR), and overall survival (OS) were compared between patients treated with and without ATBs within 30 days before and after immunotherapy. Results: No significant differences in PFS (P = 0.376) and OS (P = 0.121) were found between patients treated with and without ATBs. Univariate and multivariate analyses showed that using ATBs was not associated with PFS, DCR, and OS. Conclusion: The use of ATBs within 30 days before and after immunotherapy in patients with primary liver cancer had no adverse effects on PFS, DCR, and OS.

To reveal the mechanism of anti-renal fibrosis effects of an n-butanol extract from Amygdalus mongolica, renal fibrosis was induced with unilateral ureteral obstruction (UUO) and then treated with an n-butanol extract (BUT) from Amygdalus mongolica (Rosaceae). Sixty male Sprague-Dawley rats were randomly divided into the sham-operated, renal fibrosis (RF) model, benazepril hydrochloride-treated model (1.5 mg kg−1) and BUT-treated (1.75, 1.5 and 1.25 g kg−1) groups and the respective drugs were administered intragastrically for 21 days. Related biochemical indices in rat serum were determined and histopathological morphology observed. Serum metabolomics was assessed with HPLC-Q-TOF-MS. The BUT reduced levels of blood urea nitrogen, serum creatinine and albumin and lowered the content of malondialdehyde and hydroxyproline in tissues. The activity of superoxide dismutase in tissues was increased and an improvement in the severity of RF was observed. Sixteen possible biomarkers were identified by metabolomic analysis and six key metabolic pathways, including the TCA cycle and tyrosine metabolism, were analyzed. After treatment with the extract, 8, 12 and 9 possible biomarkers could be detected in the high-, medium- and low-dose groups, respectively. Key biomarkers of RF, identified using metabolomics, were most affected by the medium dose. A. mongolica BUT extract displays a protective effect on RF in rats and should be investigated as a candidate drug for the treatment of the disease.

ObjectiveSingle-pill amlodipine besylate (AML) plus losartan (LOS) has been used to treat inadequately controlled hypertension after antihypertensive monotherapy; however, relevant data in China are limited. This study aimed to compare the efficacy and safety of single-pill AML/LOS and LOS alone in Chinese patients with inadequately controlled hypertension after LOS treatment.MethodsIn this multicenter, double-blind, randomized, controlled phase III clinical trial, patients with inadequately controlled hypertension after 4 weeks of LOS treatment were randomized to receive daily single-pill AML/LOS (5/100 mg, AML/LOS group, N = 154) or LOS (100 mg, LOS group, N = 153) tablets for 8 weeks. At weeks 4 and 8 of treatment, sitting diastolic and systolic blood pressure (sitDBP and sitSBP, respectively) and the BP target achievement rate were assessed.ResultsAt week 8, the sitDBP change from baseline was greater in the AML/LOS group than in the LOS group (−8.84 ± 6.86 vs. −2.65 ± 7.62 mmHg, P

Significant water loss caused by pipeline leaks emphasizes the importance of effective pipeline leak detection and localization techniques to minimize water wastage. All of the state-of-the-art approaches use deep learning (DL) for leak detection and cross-correlation for leak localization. The existing methods’ complexity is very high, as they detect and localize the leak using two different architectures. This paper aims to present an independent architecture with a single sensor for detecting and localizing leaks with enhanced performance. The proposed approach combines a novel EMD with an optimal mode selector, an MFCC, and a two-dimensional convolutional neural network (2DCNN). The suggested technique uses acousto-optic sensor data from a real-time water pipeline setup in UTAR, Malaysia. The collected data are noisy, redundant, and a one-dimensional time series. So, the data must be denoised and prepared before being fed to the 2DCNN for detection and localization. The proposed novel EMD with an optimal mode selector denoises the one-dimensional time series data and identifies the desired IMF. The desired IMF is passed to the MFCC and then to 2DCNN to detect and localize the leak. The assessment criteria employed in this study are prediction accuracy, precision, recall, F-score, and R-squared. The existing MFCC helps validate the proposed method’s leak detection-only credibility. This paper also implements EMD variants to show the novel EMD’s importance with the optimal mode selector algorithm. The reliability of the proposed novel EMD with an optimal mode selector, an MFCC, and a 2DCNN is cross-verified with cross-correlation. The findings demonstrate that the novel EMD with an optimal mode selector, an MFCC, and a 2DCNN surpasses the alternative leak detection-only methods and leak detection and localization methods. The proposed leak detection method gives 99.99% accuracy across all the metrics. The proposed leak detection and localization method’s prediction accuracy is 99.54%, precision is 98.92%, recall is 98.86%, F-score is 98.89%, and R-square is 99.09%.

Abstract Background Immune checkpoint inhibitors (ICIs) have been used to successfully treat primary liver cancer (PLC); however, identifying modifiable patient factors associated with therapeutic benefits is challenging. Obesity is known to be associated with increased survival after ICI treatment; however, the relationship between body composition (muscle, fat) and outcomes is unclear. This study aimed to evaluate the association between sarcopenia and CT-derived fat content and the prognosis of ICIs for the treatment of PLC. Methods In this retrospective cohort study of 172 patients with PLC, we measured the skeletal muscle index (SMI), skeletal muscle density, visceral adipose tissue index, subcutaneous adipose tissue index, total adipose tissue index (TATI), and visceral-to-subcutaneous adipose tissue area ratio using CT. In addition, we analyzed the impact of body composition on the prognosis of the patients. Multivariate Cox regression analysis was used to screen for influencing factors. Results Among the seven body composition components, low SMI (sarcopenia) and low TATI were significantly associated with poor clinical outcomes. Multivariate analysis revealed that sarcopenia (hazard ratio [HR], 5.39; 95% confidence interval [CI], 1.74–16.74; p = 0.004) was a significant predictor of overall survival (OS). Kaplan–Meier curves showed that sarcopenia and TATI were significant predictors of OS. Body mass index was not associated with survival outcomes. Conclusions Sarcopenia and fat tissue content appear to be independently associated with reduced survival rates in patients with PLC treated with ICIs.

Abstract Background Serine/arginine-rich splicing factor 9 (SRSF9) is a classical RNA-binding protein that is essential for regulating gene expression programs through its interaction with target RNA. Whether SRSF9 plays an essential role in colorectal cancer (CRC) progression and can serve as a therapeutic target is largely unknown. Here, we highlight new findings on the role of SRSF9 in CRC progression and elucidate the underlying mechanism. Methods CRC cell lines and clinical tissue samples were used. qRT-PCR, Western blotting, immunohistochemistry (IHC), gain- and loss-of-function assays, animal xenograft model studies, bioinformatic analysis, methylated single-stranded RNA affinity assays, gene-specific m6A quantitative qRT-PCR, dual-luciferase reporter assays and RNA stability assays were performed in this study. Results The expression level of SRSF9 was higher in CRC cell lines than that in an immortal human intestinal epithelial cell line. Overexpression of SRSF9 was positively associated with lymph node metastasis and Dukes stage. Functionally, SRSF9 promoted cell proliferation, migration and invasion in vitro and xenograft growth. The results of bioinformatic analysis indicated that DSN1 was the downstream target of SRSF9. In CRC cells and clinical tissue samples, the expression of SRSF9 was positively associated with the expression of DSN1. Knockdown of DSN1 partially inhibited the SRSF9-induced phenotype in CRC cells. Mechanistically, we further found that SRSF9 is an m6A-binding protein and that m6A modifications were enriched in DSN1 mRNA in CRC cells. Two m6A modification sites (chr20:36773619–36773620 and chr20:36773645–chr20:36773646) in the SRSF9-binding region (chr20:36773597–36773736) of DSN1 mRNA were identified. SRSF9 binds to DSN1 in an m6A motif- and dose-dependent manner. SRSF9 modulates the expression of DSN1 in CRC cells. Such expression regulation was largely impaired upon methyltransferase METTL3 knockdown. Moreover, knockdown of SRSF9 accelerated DSN1 mRNA turnover, while overexpression of SRSF9 stabilized DSN1 mRNA in CRC cells. Such stabilizing was also weakened upon METTL3 knockdown. Conclusion Overexpression of SRSF9 was associated with lymph node metastasis and Dukes stage in CRC. Knockdown of DSN1 eliminated the effects by SRSF9 overexpression in CRC. Our results indicated that SRSF9 functions as an m6A-binding protein (termed “reader”) by enhancing the stability of DSN1 mRNA in m6A-related manner. Our study is the first to report that SRSF9-mediated m6A recognition has a crucial role in CRC progression, and highlights SRSF9 as a potential therapeutic target for CRC management.

Abstract Background A lack of sleep or disorder in sleep–wake cycles has been associated with metabolic impairments. However, few studies have investigated the association between daytime napping duration and the risk of non-alcoholic fatty liver disease. This study aimed to investigate the association of daytime napping duration with the risk of non-alcoholic fatty liver disease in a Chinese population. Methods This cross-sectional study analyzed data from the Health Management Center of Nanfang Hospital, Guangdong Province. A total of 3363 participants aged 20–79 years were recruited and admitted from January 20, 2018, to October 16, 2020. Non-alcoholic fatty liver disease was diagnosed using abdominal ultrasonography. The outcome was the association between daytime sleep duration and the risk of non-alcoholic fatty liver disease. Results Compared with non-nappers, long daytime nappers (≥ 60 min) were associated with a higher risk of non-alcoholic fatty liver disease in the crude model (odds ratio 2.138; 95% confidence interval 1.88–2.61, P

Abstract Background Dyslipidemia is a significant contributor to cardiovascular and cerebrovascular diseases. Research on the relationship between breakfast consumption frequency and dyslipidemia in the working population is lacking. Therefore, we aimed to investigate this relationship based on a retrospective cohort study of a large working population in China. Methods This retrospective cohort study used data from the physical examinations and questionnaire survey of working participants at Nanfang Hospital from January 20, 2015 to October 16, 2020. Univariate and multivariate analyses were conducted to explore the relationship between breakfast consumption frequency and dyslipidemia in this working population (n = 7644). Results The prevalence of dyslipidemia among the participants was 26.4%. The univariate logistic regression test showed that the breakfast consumption frequency was inversely correlated with dyslipidemia. After adjusting for multiple factors, such as sex, age, body mass index, hypertension, hyperuricaemia, diabetes, smoking status, alcohol consumption, education level, marital status, long-term exposure to kitchen oil fumes, attending business dinners, and sleep time, it was found that breakfast consumption remained inversely associated with dyslipidaemia. The odds ratio for daily breakfast consumption was 0.466 (95% confidence interval 0.283–0.770, P = 0.003). After adjusting for confounding factors, we found that the higher the frequency of breakfast consumption, the lower the odds ratios for hypertriglyceridaemia. Conclusions This study demonstrated that breakfast consumption frequency was inversely correlated with dyslipidemia. The higher the frequency of breakfast, the lower the risk of hypertriglyceridaemia. This study provides a basis on which dietary suggestions for the working population and lifestyle guidance for patients with a clinical need to prevent dyslipidemia can be made.

Abstract Here, the feature occlusion, a data augmentation method that simulates real‐life challenges on the main features of the human face for age and gender recognition is proposed. Previous methods achieved promising results on constrained data sets with strict environmental settings, but the results on unconstrained data sets are still far from perfect. The proposed method adopted three simple occlusion techniques, blackout, random brightness, and blur, and each simulates a different kind of challenge that would be encountered in real‐world applications. A modified cross‐entropy loss that gives less penalty to the age predictions that land on the adjacent classes of the ground truth class is also proposed. The effectiveness of our proposed method is verified by implementing the augmentation method and modified cross‐entropy loss on two different convolution neural networks, the slightly modified AdienceNet and the slightly modified VGG16, to perform age and gender classification. The proposed augmentation system improves the age and gender classification accuracy of the slightly modified AdienceNet network by 6.62% and 6.53% on the Adience data set, respectively. The proposed augmentation system also improves the age and gender classification accuracy of the slightly modified VGG16 network by 6.20% and 6.31% on the Adience data set, respectively.

Objective To explore the feasibility of picture naming training in improving naming ability of patients with semantic dementia (SD). Methods A total of 14 cases of semantic dementia whose the first symptom was semantic memory impairment were given picture naming training 30 min/time, twice a day, for 5 d from October 2018 to December 2020 at Xuanwu Hospital, Capital Medical University. One day before and one day after the end of training, Picture Naming Test and Boston Naming Test (BNT) were used to evaluate the naming ability. Results After training, Picture Naming Test score (65.79 ± 34.54 vs. 49.79 ± 30.85; t = ⁃ 3.297, P = 0.001) and BNT score [6.50 (4.75, 14.00) vs. 5.00 (3.00, 11.50); Z = ⁃ 2.007, P = 0.045] were higher than before training. Conclusions Picture naming training can effectively improve the naming ability of patients with semantic dementia.

All light or heavy water reactors fabricated with carbon steels suffer from flow-accelerated corrosion (FAC). The FAC degradation of SA106B with different flow velocities was investigated in terms of microstructure. As flow velocity increased, the major corrosion type changed from general corrosion to localized corrosion. Severe localized corrosion occurred in the pearlite zone, which can be the prior location for generating pits. After normalizing, the improvement in microstructure homogeneity reduced the oxidation kinetics and lowered cracking sensitivity, causing a decrease in FAC rates of 33.28%, 22.47%, 22.15%, and 17.53% at flow velocity of 0 m/s, 1.63 m/s, 2.99 m/s, and 4.34 m/s, respectively. Additionally, localized corrosion tendency was decreased by reducing the micro-galvanic effect and tensile stresses in oxide film. The maximum localized corrosion rate decreased by 21.7%, 13.5%, 13.8%, and 25.4% at flow velocity of 0 m/s, 1.63 m/s, 2.99 m/s, and 4.34 m/s, respectively.

The present research investigated the role of sex in the effect of vocal attractiveness on fairness judgment in a two-person Ultimatum Game. Each participant in the game decided whether to accept offers from a proposer who was either associated with an attractive or unattractive voice. The results showed that while participants were more likely to accept fair offers, they would also accept some unfair offers that were associated with an attractive voice. This effect of vocal attractiveness was more clearly shown by female participants, although all male and female participants took longer to make a decision when an attractive voice was associated with an offer, regardless of whether the voice was from the same sex or the opposite sex. Overall, the results inform the role of sex in the effect of vocal attractiveness and further confirm the beauty premium effect on economic bargaining, where people with an attractive voice would benefit.

Abstract Growing demand for oil and gas has driven drilling activities to deep formations and complex well structures. Drilling fluid must be able to maintain wellbore integrity and thermal stability over extended drilling time. Besides, drilling fluid should produce high rate of penetration (ROP) and low damage to formation rock. Glycol mud satisfies these criteria thanks to its unique cloud point phenomenon. When temperature exceeds cloud point temperature, glycol starts precipitate from mud by forming micelles, coats the rock surface, and plugs the small fractures in rocks. As a result, the flow of mud into rocks is restricted and wellbore stability is improved. This paper surveys more than 40 wells that were drilled with glycol mud. Field cases reported good wellbore integrity, thermal stability, high ROP, and low formation damage. Glycol mud is an excellent choice for battling well instability and high temperatures.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancers worldwide. Due to its high morbidity and mortality rates, it is urgent to find a molecular target that contributes to esophageal carcinogenesis and progression. In this research, we aimed to investigate the functions of Latent transforming growth factor β binding protein 1(LTBP1) in ESCC progression and elucidate the underlying mechanisms. Methods The tandem mass tag-based quantitative proteomic approach was applied to screen the differentially expressed proteins (DEPs) between 3 cases of ESCC tumor samples and paired normal tissues. Then the DEPs were validated in human ESCC tissues using western blot assays and GEPIA database respectively. The expression level of LTBP1 was detected in 152 cases of ESCC tissues and paired normal tissues. Loss-of-function assays were performed to detect the function of LTBP1 in vivo and in vitro. Immunofluorescence and Western blot assays were used to detect the expression of apoptosis, epithelial–mesenchymal transition (EMT) and cancer-associated fibroblasts (CAFs) markers. Results A total of 39 proteins were screened to be up-regulated (ratio > 2.0) in all three ESCC tissues. The results of immunohistochemistry assays indicated that the expression level of LTBP1 was higher in ESCC tissues than that in paired normal tissues (p

This study describes the design and implementation of a 256-bit very long instruction word (VLIW) microprocessor based on the new RISC-V instruction set architecture (ISA). Base integer RV32I and extension instruction sets, including RV32M, RV32F, and RV32D, are selected to implement our VLIW hardware. The proposed architecture packs up eight 32-bit instruction flows, each of which performs fixed operational functions to create a 256-bit long instruction format. However, one obstacle of studying new ISAs, similar to RISC-V, to design VLIW microprocessors is the lack of dedicated compilers. Developing an architecture-specific compiler is really challenging. An instruction scheduler is integrated to dynamically schedule independent instructions into the VLIW instruction format. This scheduler is used to overcome the lack of a dedicated RISC-V VLIW compiler and leverage the available RISC-V GNU toolchain. Unlike conventional VLIWs, our proposed architecture is organized into six main stages, namely, fetch, instruction scheduler, decode, execute, data memory, and writeback. The complete design is verified, synthesized, and implemented on a Xilinx Virtex-6 (xc6vlx240t-1-ff1156). Maximum synthesis frequency reaches 83.739 MHz. The proposed RISC-V-based VLIW architecture obtains an average instructions per cycle value that outperforms that of existing open-source RISC-V cores.

Objective The purpose of this study was to determine the effect of fatigue level and sex on the range of motions of the lower extremities and impulses during the jump-landing phase after performing bilateral fatiguing tasks.Methods In total, 41 healthy young adults volunteered for this study. Participants’ jump-landing trajectories were monitored using nine cameras, and ground reaction forces were measured using a force plate. Participants performed five maximal bilateral countermovement jumps as prefatiguing tasks. The fatiguing tasks consisted of maximal effort contractions of the knee extensor at 60°/s on a dynamometer until task failure, defined as the inability to reach 50% of the peak knee extension torque for three consecutive times. The post-task maximal bilateral jumps were immediately captured after the participants failed the fatiguing task. Participants were asked to perform this cycle again, performing the fatiguing contraction task until failure to reach 30% of the peak knee extension torque.Results and conclusion It was found that the knee joint was more extended in the post-30% fatiguing task, which was due to the reduction of the flexion angle of the hip and knee joints in response to fatigue level. The impulses for both sexes were reduced at the severe fatigue level. Fatigability altered jump-landing kinematics, jump heights and impulses in response to fatigue level. The post-30% fatiguing task elicited more fatigue than the post-50% fatiguing task.

Research has shown that attractive human faces enjoy an advantage in both conscious and preconscious processing. Here we examined whether this preference for attractiveness is exclusive to human faces by measuring participants’ sensitivity to the attractiveness of cat and tiger faces. Experiment 1 measured the time taken to break continuous flash suppression (b-CFS), whereas Experiment 2 measured the dominant time in binocular rivalry (BR). The results showed that attractive cat faces were detected more quickly (Experiment 1) and dominated for longer time in visual awareness (Experiment 2). However, no effect of attractiveness was found for tiger faces in Experiment 1, while attractive tiger faces also dominated for longer time in visual awareness in Experiment 2. The results provide first evidence that the preference for attractive animal faces can be shown involuntarily or without apparent conscious control. The findings suggest that human preference for facial attractiveness may contain an aesthetic element rather than being a purely adaptive means for mate choice.

As the oxidation of yak ghee is inevitable and as consumer demand for natural products continues to increase, this study aimed to enrich yak ghee with goji berry carotenoids by means of green solvent extraction and determined changes in the oxidative stability and fatty acid profiles of yak ghees during microwave heating (MW-heating) and accelerated storage. An enriched ghee (GG0) was prepared by high shear dispersion and ultrasound-assisted extraction, while a control ghee (FG0) was prepared by heating and filtration; both ghees were stored at 65 °C for 30 days and were microwave-heated (MW-heating) at 180 °C (15 and 30 min) and 200 °C for 30 min. The results showed that the carotenoid enrichment increased the oxidative stability of yak ghee during MW-heating and storage. The initial CLA and PUFA values of GG0 were not significantly different from those of FG0; SFA increased, and MUFA and TFA decreased. There was a faster rate of UFA loss and an increase in SFA and TFA in FG0 during MW-heating and storage. This indicated a protective effect of carotenoid enrichment on yak ghee. Therefore, the findings in this study support the use of goji berry carotenoids as a natural colorant and antioxidant in yak ghee. This study provides vital information for dairy processors and marketers.