Search

Abstract Nonalcoholic fatty liver disease (NAFLD) is a serious threat to public health, but its underlying mechanism remains poorly understood. In screening important genes using Gene Importance Calculator (GIC) we developed previously, ribosomal modification protein rimK-like family member A (RIMKLA) was predicted as one essential gene but its functions remained largely unknown. The current study determined the roles of RIMKLA in regulating glucose and lipid metabolism. RIMKLA expression was reduced in livers of human and mouse with NAFLD. Hepatic RIMKLA overexpression ameliorated steatosis and hyperglycemia in obese mice. Hepatocyte-specific RIMKLA knockout aggravated high-fat diet (HFD)-induced dysregulated glucose/lipid metabolism in mice. Mechanistically, RIMKLA is a new protein kinase that phosphorylates betaine-homocysteine S-methyltransferase 1 (BHMT1) at threonine 45 (Thr45) site. Upon phosphorylation at Thr45 and activation, BHMT1 eliminated homocysteine (Hcy) to inhibit the activity of transcription factor activator protein 1 (AP1) and its induction on fatty acid synthase (FASn) and cluster of differentiation 36 (CD36) gene transcriptions, concurrently repressing lipid synthesis and uptake in hepatocytes. Thr45 to alanine (T45A) mutation inactivated BHMT1 to abolish RIMKLA’s repression on Hcy level, AP1 activity, FASn/CD36 expressions, and lipid deposition. BHMT1 overexpression rescued the dysregulated lipid metabolism in RIMKLA-deficient hepatocytes. In summary, RIMKLA is a novel protein kinase that phosphorylates BHMT1 at Thr45 to repress lipid synthesis and uptake. Under obese condition, inhibition of RIMKLA impairs BHMT1 activity to promote hepatic lipid deposition.

Abstract With childhood hypertension emerging as a global public health concern, understanding its associated factors is crucial. This study investigated the prevalence and associated factors of hypertension among Chinese children. This cross-sectional investigation was conducted in Pinghu, Zhejiang province, involving 2,373 children aged 8–14 years from 12 schools. Anthropometric measurements were taken by trained staff. Blood pressure (BP) was measured in three separate occasions, with an interval of at least two weeks. Childhood hypertension was defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) ≥ age-, sex-, and height-specific 95th percentile, across all three visits. A self-administered questionnaire was utilized to collect demographic, socioeconomic, health behavioral, and parental information at the first visit of BP measurement. Random forest (RF) and multivariable logistic regression model were used collectively to identify associated factors. Additionally, population attributable fractions (PAFs) were calculated. The prevalence of childhood hypertension was 5.0% (95% confidence interval [CI]: 4.1–5.9%). Children with body mass index (BMI) ≥ 85th percentile were grouped into abnormal weight, and those with waist circumference (WC) > 90th percentile were sorted into central obesity. Normal weight with central obesity (NWCO, adjusted odds ratio [aOR] = 5.04, 95% CI: 1.96–12.98), abnormal weight with no central obesity (AWNCO, aOR = 4.60, 95% CI: 2.57–8.21), and abnormal weight with central obesity (AWCO, aOR = 9.94, 95% CI: 6.06–16.32) were associated with an increased risk of childhood hypertension. Childhood hypertension was attributable to AWCO mostly (PAF: 0.64, 95% CI: 0.50–0.75), followed by AWNCO (PAF: 0.34, 95% CI: 0.19–0.51), and NWCO (PAF: 0.13, 95% CI: 0.03–0.30). Our results indicated that obesity phenotype is associated with childhood hypertension, and the role of weight management could serve as potential target for intervention.

The objective of the study was to investigate the effect of radio frequency parameters on the thawing time and the uniformity. During the radio frequency thawing of frozen chicken breast at 27.12 MHz and 6 kW, the effects of operating parameters such as electrode gap (8, 9, 10, and 11 cm), voltage (70%, 75%, and 80%) and sample thickness (4, 5, and 6 cm) on the pattern of temperature rise and the uniformity were examined. The results showed that with decreasing electrode gap and increasing voltage and sample thickness, the temperature rise accelerated and the uniformity index decreased. The optimum parameters were determined as 9 cm and 75% for electrode gap and voltage, respectively based on the thawing time and temperature distribution. Compared with thawing at ambient temperature (20 ℃, 6 h), the thawing time with radio frequency was shortened to 54.67 min, and the total viable count, the drip loss and total volatile basic nitrogen (T-VBN) content were significantly reduced (P < 0.05). The results of this study provide a theoretical basis and technical support for the practical application of radio frequency technology in the field of meat thawing.

Background: Medical progress has often been hindered by the inherent limitations of human ability to process large volumes of data. The application of Artificial Intelligence (AI) can help overcome this constraint, particularly in the field of trauma. Purpose and Objectives: This study aims to analyze the application of artificial intelligence in the field of trauma through visualization tools, predict future research hotspots, and explore the potential applications of related technologies in the field of trauma, especially traumatic brain injury (TBI). Materials and Methods: Based on the Web of Science database, this study utilized visualization tools such as CiteSpace, VOSviewer, and SciMAT to create a knowledge map of AI applications in trauma from 1979 to 2022. Results: The analysis indicates that traumatic brain injury (TBI) will be a focal point for future research on the use of AI in trauma. Additionally, terms related to machine learning, including Artificial Neural Network and Convolutional Neural Network, are expected to be extensively employed in trauma detection and prediction. These targeted algorithms hold significant potential for groundbreaking applications in TBI. Conclusion: Artificial intelligence, especially machine learning techniques, will play a crucial role in the research and application of trauma, particularly TBI. In the future, these technologies are expected to provide new methods and perspectives for TBI detection, prediction, and treatment.

Purpose: Capillary Refill Time (CRT) measurement has gained increasing attention in the field of sepsis and septic shock. Recognizing pressure as a fundamental determinant in CRT measurement is crucial for establishing a standardized CRT measurement procedure. In this preliminary study, we elucidated the optimal pressing strength for CRT measurement by analyzing the CRTs measured under varying pressures. Method: Seventeen healthy individuals were enlisted to undergo CRT tests on their fingertips at various pressure levels. The applied force was initiated at 0.5N and incrementally increased by 0.5N until it reached 10.5N. An integrated Photoplethysmography (PPG) device was employed to capture fluctuations in light intensity. The CRT was automatically derived from the PPG signals via a specialized algorithm. The study included correlation assessment and reliability evaluation. Box plot and Bland-Altman plot were used to visualize the impact of pressure levels on CRTs. Results: A dataset of 1414 CRTs across 21 pressures showed significant differences (Kruskal-Wallis test, p

Existing deep learning-based hyperspectral anomaly detection methods typically perform anomaly detection by reconstructing a clean background. However, for the deep networks, there are many parameters that need to be adjusted. To reduce parameters of network and improve the performance of anomaly detection, a light CNN based on residual learning and background estimation was proposed. Different from traditional methods, the proposed method could directly learn anomaly features rather than background features. First, during the training stage, a background estimation method based on non-central convolution kernels was used to obtain the pseudo-background. Second, to purify the pseudo-background, a pair down-sampling method and a joint loss that combines cross-approximation background loss and consistency loss were proposed. Third, the anomaly matrix was obtained by the difference between the hyperspectral image (HSI) and the pseudo-background. Fourth, a light CNN with three layers was proposed to extract features of the anomaly matrix. Finally, during the prediction stage, anomaly detection results were calculated from the predicted anomaly matrix obtained by light CNN through the Mahalanobis distance. Experiments were conducted with multiple metrics on five real-world datasets. Compared with eight state-of-the-art methods, the proposed method achieved the superior performance in both qualitative and quantitative evaluations.

Wound age estimation is the core content in the practice of forensic medicine. Accurate estimation of wound age is a scientific question that needs to be urgently solved by forensic scientists at home and abroad. Metabolomics techniques can effectively detect endogenous metabolites produced by internal or external stimulating factors and describe the dynamic changes of metabolites in vivo. It has the advantages of strong operability, high detection efficiency and accurate quantitative results. Machine learning algorithm has special advantages in processing high-dimensional data sets, which can effectively mine biological information and truly reflect the physiological, disease or injury state of the body. It is a new technical means for efficiently processing high-throughput big data. This paper reviews the status and advantages of metabolomic techniques combined with machine learning algorithm in the research of wound age estimation, and provides new ideas for this research.

Conclusion: Impaired central sensitivity to thyroid hormones was significantly associated with the reduction of VFA and SFA, while impaired peripheral sensitivity was associated with an increase of SFA in euthyroid individuals with T2DM.

Background. Diabetes mellitus is often accompanied by dyslipidemia. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, as a novel therapeutic agent for the treatment of type 2 diabetes mellitus (T2DM), have been reported to exert effects on lipid, while the results remain controversial. This study is aimed at exploring the effect of SGLT2 inhibitor canagliflozin on lipid profile. Methods. This study was a single-center, open-label, nonrandomized, prospective study. Metformin (500 mg three times per day) or canagliflozin (100 mg, once daily) was administered for 12 weeks. Fasting blood samples were collected before and 12 weeks after treatment. Serum lipid profile levels and angiopoietin-like protein 3 (ANGPTL3) were determined. In animal experiment, C57BL/6 J mice were divided into three groups including control, STZ + HFD, and STZ + HFD + canagliflozin. Lipid profile and plasma ANGPTL3 level were measured after 12 week’s treatment. Moreover, the expression of ANGPTL3 was detected in the liver tissues. Results. There was a decreased trend in low-density lipoprotein cholesterol (LDL-c) and triglycerides (TG) after canagliflozin treatment, while canagliflozin significantly increased high-density lipoprotein cholesterol (HDL-c) level and decreased plasma ANGPTL3 level. In addition, the expression of ANGPTL3 in liver tissues decreased obviously in diabetic mice with canagliflozin treatment. Conclusions. Canagliflozin increases HDL-c level and suppresses ANGPTL3 expression in patients with T2DM and diabetic mice. The reduction of ANGPTL3 may contribute to the increase of HDL-c. However, the specific mechanism needs further research. This trial is registered with ChiCTR1900021231.

Abstract Background To estimate the incidence, risk factors, and impact on mortality and functional outcomes for early coagulopathy after the return of spontaneous circulation (ROSC) in pediatric out-of-hospital cardiac arrest (OHCA) patients. Methods A post hoc analysis of the Therapeutic Hypothermia after Pediatric Cardiac Arrest Out-of-Hospital (THAPCA-OH) trial was conducted. Early coagulopathy was defined as presence of at least one of the following coagulation abnormalities upon admission: international standard ratio (INR), platelets, and age-adjusted activated partial thromboplastin time (APTT) within 6 h after OHCA and before therapeutic hypothermia initiation. The outcomes included 28-day mortality and functional prognosis. Multivariable logistic regression models were used to explore risk factors and association between early coagulopathy and outcomes. Results Of the 227 patients included, 152 (67%) were male and the median age was 2.3 years [interquartile range (IQR), 0.7–8.6 years]. The overall 28-day mortality was 63%. The incidence of early coagulopathy was 46%. Lower age, longer duration of chest compression, lower temperature, and higher white blood cell (WBC) upon admission increased the risk of early coagulopathy. Early coagulopathy [OR, 2.20 (95% CI, 1.12–4.39), P = 0.023] was independently associated with 28-day mortality after adjusting for confounders. Conclusions Early coagulopathy occurred in almost half of pediatric patients with OHCA. Lower age, longer duration of chest compression, lower temperature, and higher WBC increased the risk. The development of early coagulopathy was independently associated with increased mortality.

Thermoelectric material is capable of realizing direct conversion between heat and electricity. Here, the authors obtain high thermoelectric performance in PbSe at low-medium temperatures by importing dense dislocations.

The wide-bandgap cubic-structure semiconductor In4SnSe4 can be regarded as a product of compositing two typical layered thermoelectric materials SnSe and In4Se3. Remarkably, In4SnSe4 inherited low thermal conductivity from its parent materials. To advance the potential thermoelectric property of In4SnSe4, we systematically investigated its crystal structure and the origin of the intrinsic low thermal conductivity. In4SnSe4 crystallized in a cubic phase (space group Pa3¯), with the lattice parameters of a = b = c = 12.66 Å. The anisotropy of InSe bonds in the lattice determined the complex structure of In4SnSe4 with 72 atoms in the primitive cell. More importantly, sound velocity and elastic properties unclosed the strong anharmonicity in In4SnSe4, which contributed greatly to the low thermal conductivity. With first-principles calculations, it was found that the lone-pair electrons from In+ mainly caused the anharmonicity in the lattice. Additionally, Br was proved to be an effective dopant for In4SnSe4 to improve the electrical transport properties. This work indicated that the complex wide-bandgap semiconductor In4SnSe4 with cubic phase and intrinsic low thermal conductivity was a new promising thermoelectric material with appropriate doping.

Abstract Background Obesity is an important risk factor for hyperuricemia. We aimed to explore the relationship between perirenal fat thickness (PrFT) and paranephric fat thickness (PnFT) and serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). Methods This was a cross-sectional study involving 257 patients with T2DM recruited from Beijing Luhe Hospital from September 2019 to May 2020. The basic and clinical information such as age, gender, duration of diabetes was collected through the medical records. All patients underwent a physical examination including height, weight, waist circumference, hip circumference, systolic blood pressures and diastolic blood pressure. The venous blood and urine samples were collected to measure SUA, fasting blood glucose, total cholesterol, triglyceride, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, serum creatinine, blood urea nitrogen and glycosylated hemoglobin. PrFT and PnFT were measured via ultrasonography. Pearson correlation test and linear regression analysis were used to analyze the association between PrFT and PnFT and SUA. Results We found that PrFT and PnFT increased according to the tertiles of SUA level (P = 0.001 and P = 0.009, respectively). In addition, the PrFT and PnFT were positively associated with SUA level (r = 0.25, P

In order to improve the accuracy of hydrological models for runoff prediction and to solve the problem of disappearing time series data break or data fluctuation due to the extension of time series, monthly runoff data from 1996 to 2015 at the Cuntan hydrological station in the upper reaches of the Yangtze River are used as the basis to develop the annual runoff prediction. Prediction of the five Intrinsic Mode Function (IMF) components and one residual from the Ensemble Empirical Mode Decomposition (EEMD) decomposition used different models of Auto-Regressive Integrated Moving Average Model (ARIMA). Except for the small errors in the first two components, the rest of the ARIMA models are highly fitted. For prediction of runoff in 2014 and 2015 based on EEMD-ARIMA model, the relative errors are 6.26% and −1.17%. Compared with the single ARIMA model and Back Propagation (BP) model, the prediction effect is better, and the prediction method is simple and clear. It is shown that the combined EEMD-ARIMA model is an efficient and useful method for the prediction of annual runoff volume. HIGHLIGHTS The study used 240 months of runoff data from Cuntan hydrological station in the upper reaches of the Yangtze River.; An annual runoff prediction model based on EEMD-ARIMA hybrid method is proposed.; The EEMD-ARIMA model outperforms the EMD-ARIMA, BP, and LSTM models.;

Objectives The optimal treatment strategy remains debatable in patients with atrial fibrillation (AF) and heart failure. Our objectives were to summarise in-hospital therapies and determine factors associated with treatment strategy selections.Design A retrospective study analysing the Improving Care for Cardiovascular Disease in China-Atrial Fibrillation (CCC-AF) project from 2015 to 2019.Setting The CCC-AF project included patients from 151 tertiary and 85 secondary hospitals across 30 provinces in China.Participants Patients with AF and left ventricular systolic dysfunction (LVSD, defined as left ventricular ejection fraction

Abstract Background Negative fluid balance (NFB) is associated with reduced extubation failure. However, whether achieving more NFB can further improve extubation outcome has not been investigated. This study aimed to investigate whether more NFB and restricted fluid intake were associated with extubation success. Methods We performed a retrospective study of adult patients with mechanical ventilation (MV) admitted to Medical Information Mart for Intensive Care (MIMIC-III) from 2001 to 2012. Patients with duration of MV over 24 hours and NFB within 24 hours before extubation were included for analysis. The primary outcome was extubation failure, defined as reintubation within 72 hours after extubation. Association between fluid balance or fluid intake and extubation outcome were investigated with multivariable logistic models. Results A total of 3433 extubation events were recorded. 1803 with NFB were included for the final analysis, of which 201(11.1%) were extubation failure. Compared with slight NFB (− 20 to 0 ml/kg), more NFB were not associated improved extubation outcome. Compared with moderate fluid intake (30 to 60 ml/kg), lower ( 60 ml/kg, OR 1.63, 95% CI [0.73, 3.35], p = 0.206) fluid intake was not associated with extubation outcome. Duration of MV, chronic obstructive pulmonary disease (COPD), hypercapnia, use of diuretics, and SAPSIIscore were associated with extubation failure. Conclusions More NFB or restricted fluid intake were not associated with reduced extubation failure in patients with NFB. However, for COPD patients, restricted fluid intake was associated with extubation success.

Abstract Background Repairing radiation-induced bone injuries remains a significant challenge in the clinic, and few effective medicines are currently available. Psoralen is a principal bioactive component of Cullen corylifolium (L.) Medik and has been reported to have antitumor, anti-inflammatory, and pro-osteogenesis activities. However, less information is available regarding the role of psoralen in the treatment of radiation-induced bone injury. In this study, we explored the modulatory effects of psoralen on skeletal stem cells and their protective effects on radiation-induced bone injuries. Methods The protective effects of psoralen on radiation-induced osteoporosis and irradiated bone defects were evaluated by microCT and pathological analysis. In addition, the cell proliferation, osteogenesis, and self-renewal of SSCs were explored. Further, the underlying mechanisms of the protective of psoralen were investigated by using RNA sequencing and functional gain and loss experiments in vitro and in vivo. Statistical significance was analyzed using Student's t test. The one-way ANOVA was used in multiple group data analysis. Results Here, we demonstrated that psoralen, a natural herbal extract, mitigated radiation-induced bone injury (irradiation-induced osteoporosis and irradiated bone defects) in mice partially by rescuing the stemness of irradiated skeletal stem cells. Mechanistically, psoralen restored the stemness of skeletal stem cells by alleviating the radiation-induced suppression of AKT/GSK-3β and elevating NRF2 expression in skeletal stem cells. Furthermore, the expression of KEAP1 in skeletal stem cells did not significantly change in the presence of psoralen. Moreover, blockade of NRF2 in vivo partially abolished the promising effects of psoralen in a murine model of irradiation-induced osteoporosis and irradiated bone regeneration. Conclusions In summary, our findings identified psoralen as a potential medicine to mitigate bone radiation injury. In addition, skeletal stem cells and AKT-GSK-3β and NRF2 may thus represent therapeutic targets for treating radiation-induced bone injury. Graphical Abstract

Abstract Background The purpose of this study was to investigate the surgical efficacy of crossing the cervicothoracic junction during posterior cervical laminectomy and fusion for the treatment of multilevel cervical ossification of the posterior longitudinal ligament (OPLL). Methods From October 2009 to October 2017, 46 consecutive patients with multilevel cervical OPLL underwent posterior cervical laminectomy and crossing the cervicothoracic junction fusion were obtained in the study. Their medical records were retrospectively collected. Cervical lordosis and cervical sagittal balance were used to assess radiographic outcomes. Japanese Orthopedic Association (JOA), axial symptom, C5 root palsy, blood loss, and operation time were used to assess clinical outcomes. The mean follow-up period was 20.7 ± 8.3 months. Results The operation time was 205.2 ± 39.8 min and the intraoperative blood loss was 352.2 ± 143.7 ml. Analysis of the final follow-up data showed significant differences in JOA score (P

The simulation of precipitation changes can provide references for the prediction and prevention of flood disasters, and has guiding significance for the comprehensive utilization of regional water resources. Precipitation forecasting is difficult due to the randomness and uncertainty of precipitation events. CEEMD can effectively overcome modal aliasing and white noise interference. The WTD process has obvious denoising effects on the original signal. GRU can effectively solve long-term memory and reflection. Based on the advantages of problems such as gradients in propagation, a CEEMD-WTD-GRU precipitation prediction coupling model is constructed. The second decomposition of CEEMD-WTD-GRU can more effectively extract complex time series information. The time series forecasting provided a new method, which effectively improved the accuracy of the forecast and applied it to the forecast of monthly precipitation in Shanghai. The research results show that the average absolute error of the CEEMD-WTD-GRU model is 3.86, the average relative error is 3.30%, and the Nash efficiency coefficient is 0.99. The prediction accuracy is better than the CEEMD-WTD-GRU model without noise reduction, the CEEMD-LSTM model and GRU model, which shows that it has strong nonlinear and complex process learning ability in hydrological factor simulation, and can be used for regional precipitation prediction. HIGHLIGHTS Complementary ensemble empirical modal decomposition (CEEMD) is a relatively novel data preprocessing method that can effectively reduce the non-smoothness of time series.; Wavelet threshold noise (WTD) reduction is an excellent noise reduction technology that can effectively reduce the noise in the signal.; Gated Recurrent Unit (GRU) as a prediction model is more adept at handling long time series.;

Rainfall prediction is a very important guideline for water resources management as well as ecological protection, and its changes are the result of multiple factors with obvious uncertainties and nonlinearities. Based on the advantages of Complete Ensemble Empirical Mode Decomposition with Adaptive Noise (CEEMDAN) non-smooth signal decomposition, the Particle Swarm Optimization (PSO) can be used to optimize the input weights and thresholds of the Extreme Learning Machine (ELM), which can effectively improve the prediction effect and accuracy of ELM, and a rainfall prediction model based on CEEMDAN-PSO-ELM is constructed. The model is applied to the monthly rainfall prediction of Zhongwei City, and the results show that the CEEMDAN-PSO-ELM coupled model has a high prediction accuracy, the mean absolute error (MAE) is 1.29, relative percentage error (RPE) is 0.45, root mean square error (RMSE) is 1.43 and the Nash efficiency coefficient (NSE) is 0.93. It has obvious advantages in hydrological simulation prediction when compared and analyzed with the deep Long-Short Term Memory (LSTM), PSO-ELM coupled model and ELM model. HIGHLIGHTS CEEMDAN is a novel data preprocessing method, which can effectively reduce the nonsmoothness of time series.; ELM has advantages in learning rate and generalization ability. PSO can optimize the input weight and threshold of ELM and effectively improve the prediction accuracy of elm.; CEEMDAN-PSO-ELM coupling model has good nonlinear and complex process learning ability in hydrological simulation.;

Abstract Background The aim of this study was to examine the possible association between serum micronutrients (vitamin D, retinol, zinc), C-reactive protein (CRP), and obesity among children and adolescents. Methods Weight and height were measured and serum 25-hydroxy vitamin D, serum retinol, serum zinc, and CRP were measured in 2818 children and adolescents (6–17 years of age), and the data of 10 investigation sites in Zhejiang Province were used. The difference of micronutrients (vitamin D, retinol, zinc) and CRP among different nutritional status were explored by ANOVA and Chi-square test. The associated factors of micronutrients and CRP of overweight and obesity were explored by multifactor analysis. Results There were significant differences between male students and female students on BMI, 25(OH)D3, and CRP, and there were significant differences between children and adolescents and between students living in urban area and rural area on BMI, 25(OH)D3, retinol, and zinc(t > 1.96, p

Abstract Background Periodontitis is a complex infectious disease with various causes and contributing factors. The aim of this study was to identify key genes, microRNAs (miRNAs) and transcription factors (TFs) and construct a miRNA–mRNA–TF regulatory networks to investigate the underlying molecular mechanism in periodontitis. Methods The GSE54710 miRNA microarray dataset and the gene expression microarray dataset GSE16134 were downloaded from the Gene Expression Omnibus database. The differentially expressed miRNAs (DEMis) and mRNAs (DEMs) were screened using the “limma” package in R. The intersection of the target genes of candidate DEMis and DEMs were considered significant DEMs in the regulatory network. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. Subsequently, DEMs were uploaded to the STRING database, a protein–protein interaction (PPI) network was established, and the cytoHubba and MCODE plugins were used to screen out key hub mRNAs and significant modules. Ultimately, to investigate the regulatory network underlying periodontitis, a global triple network including miRNAs, mRNAs, and TFs was constructed using Cytoscape software. Results 8 DEMis and 121 DEMs were found between the periodontal and control groups. GO analysis showed that mRNAs were most significantly enriched in positive regulation of the cell cycle, and KEGG pathway analysis showed that mRNAs in the regulatory network were mainly involved in the IL-17 signalling pathway. A PPI network was constructed including 81 nodes and 414 edges. Furthermore, 12 hub genes ranked by the top 10% genes with high degree connectivity and five TFs, including SRF, CNOT4, SIX6, SRRM3, NELFA, and ONECUT3, were identified and might play crucial roles in the molecular pathogenesis of periodontitis. Additionally, a miRNA–mRNA–TF coregulatory network was established. Conclusion In this study, we performed an integrated analysis based on public databases to identify specific TFs, miRNAs, and mRNAs that may play a pivotal role in periodontitis. On this basis, a TF–miRNA–mRNA network was established to provide a comprehensive perspective of the regulatory mechanism networks of periodontitis.

Objective. In this study, we aimed to estimate the impact of sleep duration on left ventricular hypertrophy (LVH) in type 2 diabetes mellitus (T2DM). Methods. Consecutive patients with T2DM undergoing transthoracic echocardiography (TTE) in our center from October 2017 to February 2021 were analyzed. The association of the risk of LVH in T2DM patients was evaluated using univariable and multivariable logistic regression analyses. Results. This study finally included 2689 adult patients (mean age 51.8 ± 12.5 years, 56.2% men, mean sleep duration 7.6 ± 1.4 hours per day). Of all patients, 655 (24.4%) patients were diagnosed with LVH and 2034 did not have LVH. All patients were adults and were diagnosed with T2DM. In the univariate and multivariate regression analyses, gender, sleep duration, body mass index (BMI), waist, hemoglobin (Hb), blood creatinine (Cr), and high-density lipoprotein cholesterol (HDL-c) were associated with LVH. In the restricted cubic spline (RCS) model, the cut-off points of sleep duration given refer to the group of patients with T2DM and LVH were 8 hours per day. With the cut-off points, the multivariable analysis demonstrated that, for diabetic patients, LVH was significantly correlated with a sleep duration of 8 hours per day, hemoglobin, blood urea nitrogen (BUN), and HDL-c. Conclusion. For patients with T2DM, long sleep duration (>8 hours per day), hemoglobin, BUN, and HDL-c were independently associated with LVH. This trial is registered with NCT03811470.

Background. Accumulating evidence has suggested a link between adipokines and diabetic retinopathy (DR). This study is aimed at investigating the risk factors for sight-threatening DR (STDR) and establishing a prognostic model for predicting STDR among a high-risk population of patients with type 2 diabetes mellitus (T2DM). Methods. Plasma concentrations of adipokines were determined by enzyme-linked immunosorbent assay. In the case-control set, principal component analysis (PCA) was performed to select optimal predictive cytokines for STDR, involving severe nonproliferative DR (NPDR) and proliferative DR. Support vector machine (SVM) was used to examine the possible combination of baseline plasma adipokines to discriminate the patients with mild NPDR who will later develop STDR. An individual prospective cohort with a follow-up period of 3 years was used for the external validation. Results. In both training and testing sets, involving 306 patients with T2DM, median levels of plasma adiponectin (APN), leptin, and fatty acid-binding protein 4 (FABP4) were significantly higher in the STDR group than those in mild NPDR. Except for adipsin, the other three adipokines, FABP4, APN, and leptin, were selected by PCA and integrated into SVM. The accuracy of the multivariate SVM classification model was acceptable in both the training set (AUC=0.81, sensitivity=71%, and specificity=91%) and the testing set (AUC=0.77, sensitivity=61%, and specificity=92%). 110 T2DM patients with mild NPDR, the high-risk population of STDR, were enrolled for external validation. Based on the SVM, the risk of each patient was calculated. More STDR occurred in the high-risk group than in the low-risk group, which were grouped by the median value of APN, FABP4, and leptin, respectively. The model was validated in an individual cohort using SVM with the AUC, sensitivity, and specificity reaching 0.77, 64%, and 91%, respectively. Conclusions. Adiponectin, leptin, and FABP4 were demonstrated to be associated with the severity of DR and maybe good predictors for STDR, suggesting that adipokines may play an important role in the pathophysiology of DR development.

Background. Acute kidney injury (AKI) is a common complication of percutaneous coronary intervention (PCI) that has been associated with high morbidity and mortality in patients with STEMI. Acute tubular damage may be reflected by serum creatinine (Scr) values that do not meet the criteria for AKI. Methods. This analysis included 19,424 patients from the Improving Care for Cardiovascular Disease in China, Acute Coronary Syndrome Project (n = 5,221 (36.8%), patients with a small increase in Scr within 48 h of hospitalization; n = 14,203 patients with no increase in Scr). The primary outcome was the incidence of major adverse cardiovascular events (MACE). Secondary outcomes included the incidence of massive hemorrhage, in-hospital death, atrial fibrillation, heart failure, cardiogenic shock, cardiac arrest, and stroke. Logistic regression analysis was used to evaluate associations between a small increase in Scr within 48 h of hospitalization (>0.1 to

An ultra-compact metasurface-based imager with modified point spread function is demonstrated to realize arbitrary all-optical parallel picture convolution that is highly compatible to convolutional neural network.

Abstract Large eyelid defect after excision of malignancies or trauma is difficult to reconstruct due to special structure and function of the eyelid. In this study, we aimed to present the outcomes of subcutaneous pedicled propeller flap for reconstructing the large eyelid defect after excision of malignancies or trauma. A retrospective review of patients diagnosed with eyelid defect due to excision of malignancies or trauma, and undergoing subcutaneous pedicled propeller flap for reconstructing the large eyelid defect, was conducted at our hospital. The clinical data were collected and analyzed. A total of 15 patients were included in the cases series. Nine patients were diagnosed with basal cell carcinoma, 3 patients with epidermoid carcinoma, and 3 patients with trauma. All the defects were successfully covered with this designed flap. There was no flap necrosis in all the cases. No functional problems were observed in all of the cases. At long-term postoperative follow-up, the average score of patients’ satisfaction was good. This subcutaneous pedicled propeller flap is a feasible alternative technique for reconstructing the large eyelid defect after excision of malignancies or trauma. This flap option could avoid the use of free flaps for large defect.

Renewable energy generation, as part of the global effort to mitigate climate change, will play a central role in reducing greenhouse gas emissions and achieving China's goal of carbon emissions peak before 2030 and carbon neutral before 2060. However, the impact of carbon quota auctions on renewable energy generation has not been sufficiently discussed. The main purpose of this study is to investigate whether China can rely on quota auctions to increase renewable energy generation in the short term, and to demonstrate which is more effective in promoting renewable energy development, policy enforcement or auction constraints? The improved neo-trans-log production model, the multi-objective linear programming model and the dispatch heuristic were used to predict additional emission reduction cost, optimized power mix with different auctioning rates, with economic development, technological progress and the unique characteristics of China's power generation industry being taken into consideration. The results show that the auctioning rate will have little influence on the optimized energy production structure, especially on the share of renewable energy resources; when the total on-grid electricity generation ranges from 7625 to 7926 billion kW h and the auctioning rate ranges from 0% to 5%, policy enforcement will influence the generation of renewable energy to a greater extent than auctioning in the near future.

Coordinated taxiing planning for multiple aircraft on flight deck is of vital importance which can dramatically improve the dispatching efficiency. In this paper, first, the coordinated taxiing path planning problem is transformed into a centralized optimal control problem where collision-free conditions and mechanical limits are considered. Since the formulated optimal control problem is of large state space and highly nonlinear, an efficient hierarchical initialization technique based on the Dubins-curve method is proposed. Then, a model predictive controller is designed to track the obtained reference trajectory in the presence of initial state error and external disturbances. Numerical experiments demonstrate that the proposed “offline planning + online tracking” framework can achieve efficient and robust coordinated taxiing planning and tracking even in the presence of initial state error and continuous external disturbances.

Abstract Background The surgical management of Mayo III/IV tumor thrombi is difficult and risky, and robotic surgery is even more difficult. The purpose of this study was to introduce the step-by-step and orderly lowering of the height of inferior vena cava tumor thrombus, which was the core technique of robot operation for Mayo III/IV tumor thrombus. Method A total of 18 patients were included in this study. The average tumor thrombus height was 2.4 cm above the level of the second porta hepatis (SPH), and 9 patients were prepared for cardiopulmonary bypass (CPB) before surgery. During the operation, the height of the tumor thrombus was lowered orderly for 2-3 times, and the blood flow blocking method was changed sequentially. The CPB was required when tumor thrombus in the atrium; After the height of the thrombus was lowered to the atrium entrance, CPB was stopped and the blood flow was blocked in the upper- and retro-hepatic inferior vena cava (IVC); After the tumor thrombus continued to descend to the lower part of the SPH, liver blood flow could be restored, and then, the blood flow was simply blocked in the retro-hepatic IVC to complete the removal of the thrombus and the repair or resection of the IVC. Finally, the diseased kidney and renal vein were removed. Results All operations were successfully completed, and 2 cases were transferred to laparotomy. Seven cases received CPB, while the other 11 did not. 15 patients underwent two times of the lowering of the tumor thrombus, 2 patients underwent one time and 1 patient underwent three times. The mean liver/IVC dissociation and vascular suspension time was 22.0 min. All patients had less than Clavien-Dindo grade III complications, no serious complications occurred during operation, and no patient died within 90 days. Conclusions The step-by-step and orderly decline of tumor thrombus height is the key to the success of robot Mayo III / IV tumor thrombus surgery. This method can shorten FPH and CPB time and improve the success rate of surgery.

Abstract Background Although the prognosis for most patients with papillary thyroid cancer (PTC) is good, the present treatment is ineffective for 5–10% patients. Several studies found sodium–glucose cotransporter 2 (SGLT2) inhibitors may inhibit the growth of tumors. However, whether SGLT2 inhibitors have therapeutic effect on thyroid cancer remains unclear. Materials and methods The levels of SGLT2 in PTC and normal thyroid tissue were assessed by immunohistochemistry and clinical dataset analysis. Cell growth was detected by the CCK-8 and colony formation. Glucose uptake into thyroid cancer cell was evaluated by 2-DG uptake assay. Glycolysis were analyzed by Seahorse XF Extracellular Flux Analysis. RNA-seq were used to screen differentially expressed genes of cells treated with/without canagliflozin (a SGLT2 inhibitor). Furthermore, flow cytometry, western blot, and gene set enrichment analysis were employed to elucidate cell cycle, apoptosis and the underlying mechanism of the anticancer effect of canagliflozin. The effect of canagliflozin on thyroid cancer growth was further confirmed in vivo through xenograft formation assay. Results SGLT2 inhibition attenuated the growth of thyroid cancer cells in vitro and in vivo. Canagliflozin inhibited glucose uptake, glycolysis and AKT/mTOR signaling activation, and increased AMPK activation in thyroid cancer cell. Furthermore, canagliflozin inhibited G1/S phase transition and cyclin D1, cyclin D3, cyclin E1, cyclin E2, and E2F1 expression levels in thyroid cancer cell. In addition, canagliflozin increased apoptosis of thyroid cancer cell. Further investigation revealed that canagliflozin could increase γ-H2AX expression levels and DNA damage response signaling ATM/CHK2 activation. In thyroid cancer patients, SGLT2 was increased in thyroid cancer and positively related to cyclin D3. Conclusions SGLT2 inhibition may limit glucose uptake resulting in energetic crisis, following oxidative stress mediated DNA damage and cell cycle arrest, which resulted to the increased cell apoptosis and decreased proliferation of thyroid cancer cells, suggesting a potential use for SGLT2 inhibitors as thyroid cancer therapeutics.

Abstract The complex interaction between cancer cells and the immune microenvironment is a central regulator of tumor growth and the treatment response. Chemotherapy-induced senescence is accompanied by the senescence-associated secretion phenotype (SASP). However, the mechanisms underlying the regulation of the SASP remain the most poorly understood element of senescence. Here, we show that nuclear erythroid factor 2-like factor 2 (Nrf2), a master antioxidative transcription factor, accumulates upon doxorubicin-induced senescence. This is due to the increased cytoplasmic Inhibitor of Apoptosis Stimulating Protein of P53, iASPP, which binds with Keap1, interrupting Keap1/Nrf2 interaction and promoting Nrf2 stabilization and activation. Activated Nrf2 transactivates a novel target gene of SASP factor, macrophage colony-stimulating factor (M-CSF), which subsequently acts on macrophages and induces polarization from M1 to M2 via a paracrine mechanism. Genetic inhibition of iASPP-Nrf2 suppresses the growth of apoptosis-resistant xenografts, with further analysis revealing that M-CSF/M-CSFR-regulated macrophage polarization is critical for the functional outcomes delineated above. Overall, our data uncover a novel function of iASPP-Nrf2 in skewing the immune microenvironment under treatment-induced senescence. Targeting the iASPP-Nrf2 axis could be a powerful strategy for the implementation of new chemotherapy-based therapeutic opportunities.

Migraine is a common and often disabling neurologic disease, its high prevalence and disability significantly impact on patients and relatives, contributing to heavy social and economic burden. However, currently available migraine treatment options are limited and are often associated with many intolerable side­effects. Therefore, it is necessary to explore new therapeutic options for migraine. This review discusses the most recent and evidence­based advances in pharmacological and non­pharmacological treatment approaches for migraine.

To investigate the genetic polymorphisms of 19 X-STR loci in the Han population in Northern China, samples from 628 unrelated individuals (314 males and 314 females) were collected and 19 X-STR loci were amplified by AGCU X19 STR System. A total of 270 different alleles were detected in 19 X-STR loci. All loci were in Hardy − Weinberg equilibrium and there was only one pair of linkage loci (DXS10103-DXS10101). There was no significant difference in allele frequency between male and female populations. The combined power of discrimination in males was 1–1.8667 × 10−13, while the combined power of discrimination in females was 1–3.6532 × 10−22. The combined mean paternity exclusion chance (CMEC) for X-chromosomal markers in father/daughter or mother/son duos Mean paternity exclusion chance (MECDesmarais Duo) was 1–5.1109 × 10−9. Moreover, the CMEC for X-chromosomal markers in trios involving daughters (MECDesmarais) was 1–2.0292 × 10−12. The compound amplification system composed of 19 X-STR in this study showed high polymorphism in the Han population of Northern China, which had a high application value in difficult genetic relationship identification.

Abstract Background AK098656 may be an adverse factor for coronary heart disease (CHD), especially in patients with hypertension. This study aimed to analyze the effect of AK098656 on CHD and CHD with various complications. Methods A total of 117 CHD patients and 27 healthy control subjects were enrolled in the study. Plasma AK098656 expression was determined using the quantitative real-time polymerase chain reaction. Student’s t-test was used to compare AK098656 expression levels in different groups. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to quantify the discrimination ability between CHD patients and health controls and between CHD and CHD + complications patients. The relationship between AK098656 and coronary stenosis was analyzed using Spearman’s correlation. Results AK098656 expression was remarkably higher in CHD patients than in healthy controls (P = 0.03). The ROC curve revealed an effective predictive AK098656 expression value for CHD risk, with an AUC of 0.656 (95% CI 0.501–0.809). Moreover, AK098656 expression was increased in CHD + complications patients compared to CHD patients alone (P = 0.005), especially in patients with hypertension (CHD + hHTN, P = 0.030). The ROC curve revealed a predictive AK098656 prognostic value for discriminating between CHD and CHD + hHTN patients, with an AUC of 0.666 (95% CI 0.528–0.805). There was no significant difference in AK098656 expression in CHD patients with diabetes mellitus compared to CHD patients alone. In addition, AK098656 expression in CHD patients was positively correlated with stenosis severity (R = 0.261, P = 0.006). Conclusion AK098656 expression was significantly increased in patients with CHD, especially those with hypertension, and its expression level was positively correlated with the degree of coronary stenosis. This implied that AK098656 may be a risk factor for CHD and can potentially be applied in clinical diagnosis or provide a novel target for treatment.

Abstract Background Renal insufficiency (RI) is a frequent comorbidity among patients with acute coronary syndrome (ACS). We aimed to evaluate the attributable risk associated with mild RI for the in-hospital outcomes in patients with ACS. Methods The Improving Care for Cardiovascular Disease in China-ACS (CCC-ACS) Project was a collaborative study of the American Heart Association and the Chinese Society of Cardiology. A total of 92,509 inpatients with a discharge diagnosis of ACS were included. The attributable risk was calculated to investigate the effect of mild RI (eGFR 60-89 ml / min · 1.73 m2) on major adverse cardiovascular events (MACEs) during hospitalization. Results The average age of these ACS patients was 63 years, and 73.9% were men. The proportion of patients with mild RI was 36.17%. After adjusting for other possible risk factors, mild RI was still an independent risk factor for MACEs in ACS patients. In the ACS patients, the attributable risk of eGFR 60-89ml/min·1.73m2 to MACEs was 7.78%, 4.69% of eGFR 45-59 ml/min·1.73m2, 4.46% of eGFR 30-44 ml/min·1.73m2, and 3.36% of eGFR

Abstract Background Recaticimab (SHR-1209, a humanized monoclonal antibody against PCSK9) showed robust LDL-C reduction in healthy volunteers. This study aimed to further assess the efficacy and safety of recaticimab in patients with hypercholesterolemia. Methods In this randomized, double-blind, placebo-controlled phase 1b/2 trial, patients receiving stable dose of atorvastatin with an LDL-C level of 2.6 mmol/L or higher were randomized in a ratio of 5:1 to subcutaneous injections of recaticimab or placebo at different doses and schedules. Patients were recruited in the order of 75 mg every 4 weeks (75Q4W), 150Q8W, 300Q12W, 150Q4W, 300Q8W, and 450Q12W. The primary endpoint was percentage change in LDL-C from the baseline to end of treatment (i.e., at week 16 for Q4W and Q8W schedule and at week 24 for Q12W schedule). Results A total of 91 patients were enrolled and received recaticimab and 19 received placebo. The dose of background atorvastatin in all 110 patients was 10 or 20 mg/day. The main baseline LDL-C ranged from 3.360 to 3.759 mmol/L. The least-squares mean percentage reductions in LDL-C from baseline to end of treatment relative to placebo for recaticimab groups at different doses and schedules ranged from −48.37 to −59.51%. No serious treatment-emergent adverse events (TEAEs) occurred. The most common TEAEs included upper respiratory tract infection, increased alanine aminotransferase, increased blood glucose, and increased gamma-glutamyltransferase. Conclusion Recaticimab as add-on to moderate-intensity statin therapy significantly and substantially reduced the LDL-C level with an infrequent administration schedule (even given once every 12 weeks), compared with placebo. Trial registration ClinicalTrials.gov , number NCT03944109

Abstract Background Colorectal cancer is the most common malignancy and the third leading cause of cancer-related death worldwide. This study aimed to identify potential diagnostic biomarkers for colorectal cancer by genome-wide plasma cell-free DNA (cfDNA) methylation analysis. Methods Peripheral blood from colorectal cancer patients and healthy controls was collected for cfDNA extraction. Genome-wide cfDNA methylation profiling, especially differential methylation profiling between colorectal cancer patients and healthy controls, was performed by methylated DNA immunoprecipitation coupled with high-throughput sequencing (MeDIP-seq). Logistic regression models were established, and the accuracy of this diagnostic model for colorectal cancer was verified using tissue-sourced data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) due to the lack of cfDNA methylation data in public datasets. Results Compared with the control group, 939 differentially methylated regions (DMRs) located in promoter regions were found in colorectal cancer patients; 16 of these DMRs were hypermethylated, and the remaining 923 were hypomethylated. In addition, these hypermethylated genes, mainly PRDM14, RALYL, ELMOD1, and TMEM132E, were validated and confirmed in colorectal cancer by using publicly available DNA methylation data. Conclusions MeDIP-seq can be used as an optimal approach for analyzing cfDNA methylomes, and 12 probes of four differentially methylated genes identified by MeDIP-seq (PRDM14, RALYL, ELMOD1, and TMEM132E) could serve as potential biomarkers for clinical application in patients with colorectal cancer.

There is a potential therapeutic application targeting brown adipose tissue (BAT). Either voluntary running or liraglutide increases the thermogenesis of BAT in type 2 diabetes mellitus, but their combined effect is not yet clarified. Male leptin receptor-deficient db/db diabetic mice (n = 24) were randomly divided into voluntary running, liraglutide, voluntary running + liraglutide, and control groups (n = 6/group). Normal male C57 mice were the negative control (n = 6). Fasting blood glucose was monitored every week, plasma insulin and lipid profiles were analyzed, and thermogenic protein expression in BAT and white adipose tissue (WAT) were analyzed by the western blot. A total of 128 metabolites associated with phosphatidylcholines, phosphatidylethanolamines, sphingomyelins, and ceramides were targeted in BAT. Compared to the control group, voluntary running or liraglutide treatment significantly lowered the blood glucose and increased the insulin level; the combined group showed a better effect than liraglutide alone. Hence, the combined treatment showed an enhanced hypoglycemic effect. Uncoupling protein 1 (UCP1) and OXPHOS protein expression in BAT and UCP1 in WAT were significantly increased after exercise training and liraglutide treatment. However, BAT metabolomics showed that compared to the control mice, nine fatty acids increased in the exercise group, six increased in the liraglutide group, and only three increased in the combined group. These results may suggest a higher hypoglycemic effect and the activation of BAT and WAT browning in the combined group.

Abstract Background The healing of bone defects can be challenging for clinicians to manage, especially after exposure to ionizing radiation. In this regard, radiation therapy and accidental exposure to gamma (γ)-ray radiation have been shown to inhibit bone formation and increase the risk of fractures. Cortical bone-derived stem cells (CBSCs) are reportedly essential for osteogenic lineages, bone maintenance and repair. This study aimed to investigate the effects of melatonin on postradiation CBSCs and bone defect healing. Methods CBSCs were extracted from C57BL/6 mice and were identified by flow cytometry. Then CBSCs were subjected to 6 Gy γ-ray radiation followed by treatment with various concentrations of melatonin. The effects of exogenous melatonin on the self-renewal and osteogenic capacity of postradiation CBSCs in vitro were analyzed. The underlying mechanisms involved in genomic stability, apoptosis and oxidative stress-related signaling were further analyzed by Western blotting, flow cytometry and immunofluorescence assays. Moreover, postradiation femoral defect models were established and treated with Matrigel and melatonin. The effects of melatonin on postradiation bone healing in vivo were evaluated by micro-CT and pathological analysis. Results The decrease in radiation-induced self-renewal and osteogenic capacity were partially reversed in postradiation CBSCs treated with melatonin (P

Background: Polypoid lesion of gallbladder (PLG) size larger than 10 mm is considered to be one of the surgical indications, but the final pathological results are mostly non-neoplastic polyps. The aim of the study was to define the risk factors to discriminate neoplastic PLG and create more precise criteria for surgical indications. Methods: A large scale, case-series study based on 2704 patients who underwent cholecystectomy for PLG was designed. Logistic regression analysis and receiver operating characteristic curve (ROC) was adopted to identify risk factors and the optimal size criteria for predicting neoplastic PLG. Results: Patients in the neoplastic group were significantly older than those in the non-neoplastic group and the average PLG size is much larger in the neoplastic group (18.5 ± 4.7 mm vs 12.6 ± 3.6 mm). Neoplastic PLGs are prone to be single and non-neoplastic polyps are usually multiple. On Multivariate logistic regression analysis, PLG size larger than 15 mm and age older than 43 years were found to be the independent risk factors to discriminate neoplastic PLG （Odds ratio 3.546 and 2.77 respectively）. The ROC curve showed that 12 mm might be the more reasonable PLG size threshold for the surgical suggestion. Conclusions: Considering its moderate diagnostic accuracy, the size of gallbladder polyp larger than 10 mm is insufficient to indicate surgical therapy for PLG and 12 mm should be the more optimal polyp's size threshold. Patients older than 43 years have a higher risk of having neoplastic polyps.

Precipitation forecasting is an important guide to the prevention and control of regional droughts and floods, the rational use of water resources and the ecological protection. The precipitation process is extremely complex and is influenced by the intersection of many variables, with significant randomness, uncertainty and non-linearity. Based on the advantages that complementary ensemble empirical modal decomposition (CEEMD) can effectively overcome modal aliasing, white noise interference, and the ability of long short-term memory (LSTM) networks to handle problems such as gradient disappearance. A CEEMD–LSTM coupled long-term and short-term memory network model was developed and adopted for monthly precipitation prediction of Zhengzhou City. The performance shows that the CEEMD–LSTM model has a mean absolute error of 0.056, a root mean square error of 0.153, a mean relative error of 2.73% and a Nash efficiency coefficient of 0.95, which is better than the CEEMD–Back Propagation (BP) neural network model, the LSTM model and the BP model in terms of prediction accuracies. This demonstrates its powerful nonlinear and complex process learning capability in hydrological factor simulation for regional precipitation prediction. HIGHLIGHTS Complementary ensemble empirical modal decomposition (CEEMD) is a relatively novel data preprocessing method that can effectively reduce the non-smoothness of time series.; Long short-term memory network (LSTM) as a prediction model is more adept at handling long time series.; The CEEMD–LSTM coupled has better nonlinear and complex process learning ability in hydrological factor simulation.;

Hunting behavior typically contains a sequential motor program, including search, chase, attack, and consumption. Here, the authors show that periaqueductal gray neuronal ensembles encode the sequential hunting motor program, which might provide a framework for decoding complex instinctive behaviors.

Abstract The Central Plains has a long history, rich culture, unique geographical advantages, and profound cultural heritage. The occurrence of ancient cities in the Central Plains marks the formation of Chinese state-level societies. The number, size, and distribution of ancient cities have changed greatly from the late Yangshao to the Xia and Shang Dynasties, which reflects the evolution of settlement and social organization. In this study, Geographic Information System (GIS) spatial database technology was used to establish a spatiotemporal database of ancient cities in the late Yangshao, Longshan, as well as Xia and Shang Dynasties in the Central Plains. This paper uses GIS spatial analysis technology to analyze the relationship between the ancient city distribution and the geographical environment, as well as the evolution of ancient city's shapes and sizes. Furthermore, by using the method of the nearest neighbor distance and gravity center analysis, this paper discusses the agglomeration characteristics and gravity center evolution of ancient cities. The results show that: (1) Most of the ancient cities were distributed in areas below 500 m and within 3 km from the river during the time interval from the late Yangshao to Xia and Shang Dynasties; (2) The shape of the ancient cities gradually changed from circles to squares in the Central Plains, which became a unified model for the later ancient city design; (3) The sizes of the 18 ancient cities in the Yangshao period shared high similarity, with an average area of 20 hectares. The sizes of 24 ancient cities in the Longshan period increased significantly, with an average of 39 hectares. During the Xia and Shang Dynasties, there were 22 ancient cities with an average size of 340 hectares, and the grade of sizes became obvious, marking the entrance into Chinese state-level societies; (4) Cities were scattered in the decentralized pattern during the late Yangshao and Longshan periods, whereas they became agglomerative in Xia and Shang Dynasties. This reflects the evolution of the spatial scopes and social organizational forms; and (5) From the late Yangshao to Xia and Shang Dynasties, the gravity center of ancient cities moved around the Songshan Mountain from the northwest to the southeast and again to the northeast.

Abstract Background Evidence suggests gut microbiome is associated with diabetes. However, it’s unclear whether the association remains in non-diabetic participants. A Chinese monozygotic twin study, in which the participants are without diabetes, and are not taking any medications, was conducted to explore the potential association. Methods Nine pairs of adult monozygotic twins were enrolled and divided into two twin-pair groups (a and b). Clinical and laboratory measurements were conducted. Visceral adipose tissue (VAT) was assessed. Fecal samples were collected to analyze the microbiome composition by 16S rDNA gene amplicon sequencing. Liquid chromatography mass spectrometry was performed to detect the metabolites. Results The participants aged 53 years old averagely, with 8 (88.9%) pairs were women. All the participants were obese with VAT higher than 100 cm2 (152.2 ± 31.6). There was no significant difference of VAT between the twin groups (153.6 ± 30.4 cm2 vs. 150.8 ± 29.5 cm2, p = 0.54). Other clinical measurements, including BMI, lipid profiles, fasting insulin and blood glucose, were also not significantly different between groups (p ≥ 0.056), whereas HbA1c level of group a is significantly higher than group b (5.8 ± 0.3% vs. 5.6 ± 0.2%, p = 0.008). The number and richness of OTUs are relatively higher in group a, and 13 metabolites were significantly different between two groups. Furthermore, several of the 13 metabolites could be significantly linked to special taxons. The potential pathway involved drug metabolism-other enzymes, Tryptophan metabolism and Citrate cycle. Conclusions Gut microbiome composition and their metabolites may modulate glucose metabolism in obese adults without diabetes, through Tryptophan metabolism, Citrate cycle and other pathways.

Background: Obesity is known as a common risk factor for osteoporosis and type 2 diabetes mellitus (T2DM). Perirenal fat, surrounding the kidneys, has been reported to be unique in anatomy and biological functions. This study aimed to explore the relationship between perirenal fat and bone metabolism in patients with T2DM. Methods: A total of 234 patients with T2DM were recruited from September 2019 to December 2019 in the cross-sectional study. The biochemical parameters and bone turnover markers (BTMs) were determined in all participants. Perirenal fat thickness (PrFT) was performed by ultrasounds via a duplex Doppler apparatus. Associations between PrFT and bone metabolism index were determined via correlation analysis and regression models. Results: The PrFT was significantly correlated with β-C-terminal telopeptides of type I collagen (β-CTX) (r = −0.14, P < 0.036), parathyroid hormone (iPTH) (r = −0.18, P ≤ 0.006), and 25 hydroxyvitamin D (25-OH-D) (r = −0.14, P = 0.001). Multivariate analysis confirmed that the association of PrFT and β-CTX (β = −0.136, P = 0.042) was independent of other variables. Conclusion: This study showed a negative and independent association between PrFT and β-CTX in subjects with T2DM, suggesting a possible role of PrFT in bone metabolism. Follow-up studies and further research are necessary to validate the associations and to elucidate the underlying mechanisms.

Abstract Emerging evidence indicates that circRNAs are broadly expressed in osteosarcoma (OS) cells and play a crucial role in OS progression. Recently, cancer-specific circRNA circPRKAR1B has been identified by high-throughput sequencing and is recorded in publicly available databases. Nevertheless, the detailed functions and underlying mechanisms of circPRKAR1B in OS remains poorly understood. By functional experiments, we found that circPRKAR1B enhanced OS cell proliferation, migration, and promotes OS epithelial–mesenchymal transition (EMT). Mechanistic investigations suggested that circPRKAR1B promotes OS progression through sponging miR-361-3p to modulate the expression of FZD4. Subsequently, we identified that EIF4A3 promoted cirPRKAR1B formation through binding to the downstream target of circPRKAR1B on PRKAR1B mRNA. Further rescue study revealed that overexpression of the Wnt signalling could impair the onco-suppressor activities of the silencing of circPRKAR1B. Interestingly, further experiments indicated that circPRKAR1B is involved in the sensitivity of chemoresistance in OS. On the whole, our results demonstrated that circPRKAR1B exerted oncogenic roles in OS and suggested the circPRKAR1B/miR-361-3p/FZD4 axis plays an important role in OS progression and might be a potential therapeutic target.

Abstract We test the cosmic anisotropy in the dipole-modulated $$\Lambda $$ Λ CDM model and Finslerian cosmological model with the recently-released quasar sample. Based on the redshift tomographic method, the quasar sample is divided into two subsets $$z \le z_{cut}$$ z ≤ z cut and $$z > z_{cut}$$ z > z cut by different cutting redshifts. The dipole amplitudes of the two cosmological models from the subsets $$z \le z_{cut}$$ z ≤ z cut are very weak. We find that quasars at a higher redshift range may provide more detailed information about the dipole amplitude $$A_D$$ A D . The dipole directions of each cosmological model from the subsets $$z \le 1.1$$ z ≤ 1.1 and $$z > 1.1$$ z > 1.1 are deviated by $$1\sigma $$ 1 σ level. The Pantheon sample is combined with the two subsets. The dipole amplitude from the two combined datasets is also very weak. In the dipole-modulated $$\Lambda $$ Λ CDM model, the dipole direction from the combined dataset quasar at $$z \le 1.1$$ z ≤ 1.1 and Pantheon sample is far away from the one given by the Pantheon sample. In the Finslerian cosmological model, the dipole directions from the two combined datasets are close to the one in the Pantheon sample.