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Gnaphalium affine is a plant with various active properties and has been approved for use as a traditional medicine and food ingredient. In this study, liquid chromatography with electrochemical detection was utilized to separate the antioxidant compounds of G. affine, in conjunction with liquid chromatography-triple quadrupole mass spectrometry for identification. The in vitro antioxidant activity of G. affine was evaluated using DPPH and ABTS radical scavenging capacity assays, as well as the ferric reducing antioxidant power assay. The results showed that a total of 25 antioxidant compounds were screened and identified, among which 14 compounds were quantitatively analyzed. G. affine was found to be rich in phenolic substances, with the total phenolic content ranging from 14.62 to 59.30 mg GAE/g DW, which exhibited high antioxidant potential. The antioxidant activities showed a strong positive correlation with the total phenolic content (r > 0.9). The predominant phenolic compounds in G. affine were 5-O-caffeoylquinic acid, 3-O-caffeoylquinic acid, ferulic acid, luteolin-7-O-glucoside, 3,5-O-dicaffeoylquinic acid, 1,5-O-dicaffeoylquinic acid, and luteolin, with 3,5-O-dicaffeoylquinic acid and 1,5-O-dicaffeoylquinic acid exhibiting the highest levels. Statistical analysis indicated that monosubstituted caffeoylquinic acids, disubstituted caffeoylquinic acids, and luteolin derivatives strongly correlated with the antioxidant potential. This study identified and quantified the major chemical constituents responsible for the antioxidant properties of G. affine, demonstrating its potential as a natural source of antioxidants for the use in foods, pharmaceuticals, and health products.

BackgroundInterferon-alpha1b (IFN-α1b) has shown remarkable therapeutic potential as adjuvant therapy for melanoma. This study aimed to develop five machine learning models to evaluate the efficacy of postoperative IFN-α1b in patients with advanced melanoma.MethodsWe retrospectively analyzed 113 patients with the American Joint Committee on Cancer (AJCC) stage III-IV melanoma who received postoperative IFN-α1b therapy between July 2009 and February 2024. Recurrence-free survival (RFS) and overall survival (OS) were assessed using Kaplan-Meier analysis. Five machine learning models (Decision Tree, Cox Proportional Hazards, Random Forest, Support Vector Machine, and LASSO regression) were developed and compared for their capacity to predict the outcomes of patients. Model performance was evaluated using concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves, and decision curve analysis.ResultsThe 1-year, 2-year, and 3-year RFS rates were 71.10%, 43.10%, and 31.10%, respectively. For OS, the 1-year, 2-year, and 3-year OS rates were 99.10%, 82.30%, and 75.00%, respectively. The Decision Tree (DT) model demonstrated superior predictive performance with the highest C-index of 0.792. Time-dependent ROC analysis for predicting 1-, 2-, and 3-year RFS based on the DT model is 0.77, 0.79 and 0.76, respectively. Serum albumin emerged as the important predictor of RFS.ConclusionsOur study demonstrates the considerable efficacy DT model for predicting the efficacy of adjuvant IFN-α1b in patients with advanced melanoma. Serum albumin was identified as a key predictive factor of the treatment efficacy.

Expansive soils, known for their significant volume change with variations in moisture content, are widely distributed around the globe. Due to their swelling properties, expansive soils pose significant engineering challenges, especially in rapidly developing countries like China. This study aims to investigate the swelling mechanisms of expansive soils, focusing on the influence of crack characteristics on swelling behavior. The research methodology includes field investigations, laboratory experiments, and theoretical modeling. By comprehensively considering crack rate, dry density, initial moisture content, and overburden load, a nonlinear regression swelling model is proposed in this research. The degree of crack development in expansive soils is quantitatively characterized by the content of filling materials, leading to the establishment of a crack rate model for expansive soils. Swelling tests on expansive soils with different crack contents were conducted. The results show that the swelling rate is negatively correlated with the initial moisture content and positively correlated with dry density and crack rate. Additionally, the larger the crack rate, the more significant the change in the swelling rate. Furthermore, model validation confirms that this nonlinear regression model accurately describes the relationship between swelling rate and influencing factors. It offers a more precise prediction tool for infrastructure design and maintenance in expansive soil areas, advancing geotechnical engineering practices.

Abstract To systematically analyze the damage caused by bedrock and overburden layer slope under seismic action, a set of large-scale shaking table test was designed and completed. Interpolation of the acceleration amplification coefficient, Hilbert–Huang transform and transfer function was adopted. The damage mechanisms of the bedrock and overburden layer slopes under seismic action are systematically summarized in terms of slope displacement, acceleration field, vibration amplitude, energy, vibration frequency, and damage level. The results show a significant acceleration amplification effect within the slope under seismic action and a localized amplification effect at the top and trailing edges of the slope. With an increase in the input seismic intensity, the difference in the vibration amplitude between the overburden layer and bedrock increased, low-frequency energy of the overburden layer was higher than that of the bedrock, and the vibration frequency of the overburden layer was smaller than that of the bedrock. These differences cause the interface to experience cyclic loading continuously, resulting in the damage degree of the overburden layer at the interface being larger than that of the bedrock, reduction of the shear strength, and eventual formation of landslides. The displacement in the middle of the overburden is always greater than that at the top. Therefore, under the action of an earthquake and gravity, the damage mode of the bedrock and overburden layer slope is such that the leading edge of the critical part pulls and slides at the trailing edge, and multiple tensile cracks are formed on the slope surface.

This study aims to analyze the correlation between Systemic Inflammatory Response Index (SIRI) and the severity of coronary artery stenosis in patients with coronary heart disease (CHD). It also aims to assess the predictive value of SIRI for the severity of coronary artery stenosis. A total of 2990 patients who underwent coronary angiography were included in this study. The Gensini score was used to estimate the severity of coronary vascular lesions. The predictive ability of SIRI for CHD was evaluated using receiver operating characteristic (ROC) curves. Binary multivariate logistic regression analysis was used to predict the likelihood of CHD based on the SIRI index. The results showed that people with higher SIRI index were more likely to have CHD (P < 0.001). After controlling for other risk factors, the highest quartile had a significantly higher incidence of coronary artery disease compared to the lowest quartile (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.73-3.92, P < 0.001). Furthermore, the Gensini score was significantly higher in the fourth quartile group (T4) compared to the first (T1) and second (T2) quartile groups (P < 0.001). Additionally, the SIRI index was significantly higher in the group with severe coronary artery lesions compared to the mild and moderate groups (P < 0.001). The SIRI index also showed a higher predictive ability for the extent of coronary lesions under the ROC curve compared to other commonly used markers, including platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) (P < 0.001). Therefore, SIRI index positively correlates with coronary artery stenosis in CHD patients, serving as an effective early screening marker for assessing stenosis severity.

This comprehensive review delves into the complex interplay between mitochondrial gene defects and pancreatic cancer pathogenesis through a multiomics approach. By amalgamating data from genomic, transcriptomic, proteomic, and metabolomic studies, we dissected the mechanisms by which mitochondrial genetic variations dictate cancer progression. Emphasis has been placed on the roles of these genes in altering cellular metabolic processes, signal transduction pathways, and immune system interactions. We further explored how these findings could refine therapeutic interventions, with a particular focus on precision medicine applications. This analysis not only fills pivotal knowledge gaps about mitochondrial anomalies in pancreatic cancer but also paves the way for future investigations into personalized therapy options. This finding underscores the crucial nexus between mitochondrial genetics and oncological immunology, opening new avenues for targeted cancer treatment strategies.

Abstract Purpose The pathological diagnosis and prognosis prediction of hepatocellular carcinoma (HCC) is challenging due to the lack of specific biomarkers. This study aimed to validate the diagnostic and prognostic efficiency of Kidney-type glutaminase (GLS1) for HCC in prospective cohorts with a large sample size. Methods A total of 1140 HCC patients were enrolled in our prospective clinical trials. Control cases included 114 nontumour tissues. The registered clinical trial (ChiCTR-DDT-14,005,102, chictr.org.cn) was referred to for the exact protocol. GLS1 immunohistochemistry was performed on the whole tumour section. The diagnostic and prognostic performances of GLS1 was evaluated by the receiver operating characteristic curve and Cox regression model. Results The sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and area under the curve of GLS1 for the diagnosis of HCC were 0.746, 0.842, 0.979, 0.249, 0.588, and 0.814, respectively, which could be increased to 0.846, 0.886, 0.987,0.366, 0.732, and 0.921 when combined with glypican 3 (GPC3) and alpha-fetoprotein (AFP), indicating better diagnostic performance. Further, we developed a nomogram with GPC3 and GLS1 for identifying HCC which showed good discrimination and calibration. GLS1 expression was also related with age, T stage, TNM stage, Edmondson–Steiner grade, microvascular invasion, Ki67, VEGFR2, GPC3, and AFP expression in HCC. GLS1 expression was negatively correlated with disease-free survival (P

Abstract Background Chronic stress promotes most hallmarks of cancer through impacting the malignant tissues, their microenvironment, immunity, lymphatic flow, etc. Existing studies mainly focused on the roles of stress-induced activation of systemic sympathetic nervous system and other stress-induced hormones, the organ specificity of chronic stress in shaping the pre-metastatic niche remains largely unknown. This study investigated the role of chronic stress in remodeling lung pre-metastatic niche of breast cancer. Methods Breast cancer mouse models with chronic stress were constructed by restraint or unpredictable stress. Expressions of tyrosine hydroxylase, vesicular acetylcholine transporter (VAChT), EpCAM and NETosis were examined by immunofluorescence and confocal microscopy. mRNA and protein levels of choline acetyltransferase (ChAT), VAChT, and peptidylarginine deiminase 4 were detected by qRT-PCR and Western blotting, respectively. Immune cell subsets were analyzed by flow cytometry. Acetylcholine (ACh) and chemokines were detected by ELISA and multi chemokine array, respectively. ChAT in lung tissues from patients was examined by immunohistochemistry. Results Breast cancer-bearing mice suffered chronic stress metastasized earlier and showed more severe lung metastasis than did mice in control group. VAChT, ChAT and ChAT+ epithelial cells were increased significantly in lung of model mice undergone chronic stress. ACh and chemokines especially CXCL2 in lung culture supernatants from model mice with chronic stress were profoundly increased. Chronic stress remodeled lung immune cell subsets with striking increase of neutrophils, enhanced NETosis in lung and promoted NETotic neutrophils to capture cancer cells. ACh treatment resulted in enhanced NETosis of neutrophils. The expression of ChAT in lung tissues from breast cancer patients with lung metastasis was significantly higher than that in patients with non-tumor pulmonary diseases. Conclusions Chronic stress promotes production of CXCL2 that recruits neutrophils into lung, and induces pulmonary epithelial cells to produce ACh that enhances NETosis of neutrophils. Our findings demonstrate for the first time that chronic stress induced epithelial cell derived ACh plays a key role in remodeling lung pre-metastatic niche of breast cancer.

Abstract Background The prognosis of patients undergoing hepatectomy combined with transarterial chemoembolization (TACE) and TACE alone was examined in order to better understand the role of hepatectomy in the treatment of hepatocellular carcinoma (HCC). In this work, we also created a model and investigated the variables influencing overall survival (OS) in HCC patients. Methods Retrospective analysis of 1083 patients who received TACE alone as the control group and 188 patients who received TACE after surgery in a total of 1271 HCC patients treated with LR + TACE or TACE at three third-class hospitals in China. It was done using the Propensity Score Matching (PSM) technique. The differences in OS between the two groups were compared, and OS-influencing factors were looked at. The main endpoint is overall survival. In this study, the COX regression model was used to establish the nomogram. Results The median OS of the LR + TACE group was not attained after PSM. The median OS for the TACE group was 28.8 months (95% CI: 18.9–38.7). The median OS of the LR + TACE group was higher than that of the TACE group alone, indicating a significant difference between the two groups (χ2 = 16.75, P 0.05); Regarding the median OS for patients with distant metastases, which was not achieved and 8.5 months, respectively, there was a significant difference between the two groups (χ2 = 5.759, P = 0.016). We created a new nomogram to predict 1-, 2-, and 3-year survival rates based on multiple independent predictors in COX multivariate analysis. The cohort's C-index is 0.705. The area under the curve (AUC value) for predicting 1-, 2-, and 3-year survival rates were shown by the subject operating characteristic (ROC) curve linked to the nomogram to be 0.730, 0.728, and 0.691, respectively. Conclusions LR + TACE can increase OS, delay tumor recurrence, and improve prognosis in HCC patients when compared to TACE alone. Additionally, the nomogram we created does a good job of forecasting the 1-year survival rate of hepatocellular carcinoma.

Abstract A common practice adopted for the pseudorange bias estimation and calibration assumes that Global Navigation Satellite System satellite-dependent pseudorange biases vary gently over time. Whereupon satellite pseudorange biases are routinely estimated and provided as the products with low temporal resolution, e.g., hourly or daily, by the agencies. The story sounds unquestionably perfect under the acquainted assumption. To validate the inadequacy of the above hypothesis we herein present an approach to the estimate the BeiDou Navigation Satellite System (BDS) pseudorange biases with high temporal resolution. Its feasibility, affecting factors, and necessity are discussed. Concretely, the Geometry-Free function models are first constructed to retrieve the linear combination of the pseudorange biases; then the pseudorange Observable-specific Signal Bias (OSB) values with respect to baseline frequencies (e.g., BDS C2I/C6I) are estimated along with the ionosphere modeling; subsequently, all multi-frequency pseudorange OSBs are determined by using the ionospheric information with constraint conditions; finally, the possible Differential Code Bias sets are attainable with the estimated pseudorange OSBs. Using the observation data of four months when the estimated BDS pseudorange biases are stable, their reliability is demonstrated with the stability at the level of sub-nanosecond and the BeiDou-3 Navigation Satellite System (BDS-3) values more stable than that of BeiDou-2 Navigation Satellite System (BDS-2). The comparison between the estimated pseudorange biases and the Chinese Academy of Sciences products reveals that the accuracy of the estimated pseudorange biases is 0.2–0.4 ns. Moreover, the large magnitude of the short-term pseudorange bias variation in the tens of nanoseconds for the BDS-2 and BDS-3 are found in years 2021 and 2022, which are affected by two types of the satellite flex power for the BDS-2 and BDS-3, respectively. We stress that it’s necessary to estimate the BDS pseudorange biases with high temporal resolution in the case of the satellite flex power and the products currently provided by the agencies cannot reflect the true quantity under the circumstance.

The digital economy is developing rapidly worldwide, which is of great strategic significance in leading and driving the process of high-quality and high-efficiency development of the economy. It has gradually become a new engine to promote China’s economic growth. Therefore, it is vital to establish a digital economy indicator system. In this context, according to the connotation of digital economy, comprehensively consider the four dimensions of digital foundation, digital application, digital innovation and digital benefit, and build a full-scale digital economy indicator system. However, some previous literature proposed operating the K-means clustering algorithm in optimizing the index system. The algorithm, susceptible to the initial selection of cluster center, generates completely different clustering results with other random seed points and is thus unsuitable for optimizing the index system. Based on this, the advantages of GRA, SA, and K-means algorithms are combined to propose a K-means-SA algorithm that can obtain the global optimal solution. Then, by combining the K-means SA algorithm and the rough set algorithm, the constructed index system is further optimized. Ultimately, it establishes a set of all-round, multi-system and multi-dimensional digital economy index systems, which is of great reference significance for formulating relevant policies, provides scientific index support for the subsequent extension of digital economy theory, and promotes the benign growth of the worldwide economy.

Abstract With the advancements in radiotherapy (RT) in recent years, several studies have shown that RT can significantly prolong the survival of patients with hepatocellular carcinoma (HCC). As a noninvasive treatment option, the application of RT for the treatment of HCC is garnering increasing attention. In this retrospective study, we included data from 13,878 patients with HCC from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019 and 325 patients with HCC treated in three tertiary hospitals in China between 2015 and 2021. Patient data were divided into RT and non-RT groups based on whether the patients underwent RT. Propensity score matching analysis was performed to minimize the deviation between the RT and non-RT groups, and the Kaplan–Meier method, Cox proportional hazard model, and nomogram were used to assess the efficacy of undergoing RT. The median overall survival (mOS) of the RT group was significantly longer compared with that of the non-RT group for the SEER data (16 months versus 9 months, p

Introduction and Objectives: We initiated this study to explore the efficacy of camrelizumab combined with transcatheter arterial chemoembolization (TACE) plus sorafenib or lenvatinib versus TACE plus sorafenib or Lenvatinib for unresectable hepatocellular carcinoma (HCC). Materials and Methods: From June 2019 to November 2022, 127 advanced HCC patients were retrospectively analyzed in this study. This consisted of 44 patients that received camrelizumab plus TACE plus sorafenib or lenvatinib (triple therapy group) and 83 patients that received TACE plus sorafenib or lenvatinib (double treatment group). The overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR) were compared between the two patient groups. Results: Our findings demonstrated that patients received the triple therapy exhibited superior median OS (15.8 vs. 10.3 months, P=0.0011) and median PFS (7.2 vs. 5.2 months, P=0.019) compared to the double treatment group. In addition, the triple therapy group exhibited better 6-month (93.5% vs. 66.3%), 12-month (67.2% vs. 36.3%), and 24-month (17.2% vs. 7.6%) survival rates than the double treatment group. However, the ORR (43.2% vs. 28.9%, P = 0.106) and DCR (93.2% vs. 81.9%, P = 0.084) of the two groups were similar. Subgroup analysis showed that compared with the double treatment group, the triple therapy group had a better mOS for HCC with HBV (15.8 vs. 9.6 months, P = 0.0015) and tumor diameter ≥ 5cm (15.3 vs. 9.6 months, P = 0.00055). Conclusions: Camrelizumab plus TACE and sorafenib or lenvatinib may be a promising treatment approach for the clinical management of unresectable HCC patients.

BackgroundThe optimal local treatment for HCC with tumor diameter ≥ 5 cm is not well established. This research evaluated the effectiveness of external beam radiation therapy (EBRT) versus transcatheter arterial chemoembolization (TACE) for HCC with tumor diameter ≥ 5 cm.MethodsA total of 1210 HCC patients were enrolled in this study, including 302 and 908 patients that received EBRT and TACE, respectively. Propensity score matching (PSM) was used to identify patient pairs with similar baseline characteristics. Overall survival (OS) was the primary study endpoint.ResultsWe identified 428 patients using 1:1 PSM for survival comparison. Compared with the TACE group, the EBRT group had a significantly longer median OS (mOS) before (14.9 vs. 12.3 months, p = 0.0085) and after (16.8 vs. 11.4 months, p = 0.0026) matching. In the subgroup analysis, compared with the TACE group, the EBRT group had a significantly longer mOS for HCC with tumor diameters of 5-7 cm (34.1 vs. 14.3 months, p = 0.04) and 7-10 cm (34.4 vs. 10 months, p = 0.00065), whereas for HCC with tumor diameters ≥ 10 cm, no significant difference in mOS was observed (11.2 vs. 11.2 months, p = 0.83). In addition, the multivariable Cox analysis showed that Child-A, alkaline phosphatase < 125 U/L, and EBRT were independent prognostic indicators for longer survival.ConclusionEBRT is more effective than TACE as the primary local treatment for HCC with tumor diameter ≥ 5 cm, especially for HCC with tumor diameter of 5-10 cm.

Abstract Objectives Pulmonary lesion is frequently seen in ANCA-associated vasculitis (AAV) patients primarily due to AAV lung involvement or infection, which are hard to differentiate due to their high similarity in clinical manifestations. We aimed to analyze the clinical features of pulmonary lesions consequent to AAV involvement or infection in AAV patients and further identify the markers for differential diagnosis. Methods 140 AAV patients who admitted to the Renmin Hospital of Wuhan University from January 2016 to July 2021 were included in this study. According to the nature of lung conditions, these patients were divided into the non-pulmonary lesion group, the lung infection group and the non-pulmonary infection group, and their demographics, clinical symptoms, imaging features, as well as laboratory findings were compared. A receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of single biomarker and composite biomarkers on pulmonary infection was then evaluated. Results The patients in the lung infection group were significantly older than those in the no lesion group (63.19 ± 14.55 vs 54.82 ± 15.08, p = 0.022). Patients in the lung infection group presented more frequent symptoms and more obvious pulmonary image findings. Compared with patients in the non-pulmonary infection group, patients in the lung infection group showed a higher symptom incidence of fever, chest tightness, cough and expectoration, and hemoptysis (52.94% vs 16.00%, 61.76% vs 40.00%, 72.06% vs 46.00%, 27.94% vs 8.00%, p

Abstract Background The gene encoding the E3 ubiquitin ligase substrate-binding adapter Speckle-type BTB/POZ protein (SPOP) is frequently mutated in prostate cancer (PCa) and endometrial cancer (EC); however, the molecular mechanisms underlying the contribution of SPOP mutations to tumorigenesis remain poorly understood. Methods BRAF harbors a potential SPOP-binding consensus motif (SBC) motif. Co-immunoprecipitation assays demonstrated that BRAF interacts with SPOP. A series of functional analyses in cell lines were performed to investigate the biological significance of MAPK/ERK activation caused by SPOP mutations. Results Cytoplasmic SPOP binds to and induces non-degradative ubiquitination of BRAF, thereby reducing the interaction between BRAF and other core components of the MAPK/ERK pathway. SPOP ablation increased MAPK/ERK activation. EC- or PCa-associated SPOP mutants showed a reduced capacity to bind and ubiquitinate BRAF. Moreover, cancer-associated BRAF mutations disrupted the BRAF-SPOP interaction and allowed BRAF to evade SPOP-mediated ubiquitination, thereby upregulating MAPK/ERK signaling and enhancing the neoplastic phenotypes of cancer cells. Conclusions Our findings provide new insights into the molecular link between SPOP mutation-driven tumorigenesis and aberrant BRAF-dependent activation of the MAPK/ERK pathway.

In this paper, we define a new area-type filter algorithm based on the trust-region method. A relaxed trust-region quadratic correction subproblem is proposed to compute the trial direction at the current point. Consider the objective function and the constraint violation function at the current point as a point pair. We divide the point pairs into different partitions by the dominant region of the filter and calculate the contributions of the point pairs to the area of the filter separately. Different from the conventional filter, we define the contribution as the filter acceptance criterion for the trial point. The nonmonotone area-average form is also adopted in the filter mechanism. In this paper, monotone and nonmonotone methods are proposed and compared with the numerical values. Furthermore, the algorithm is proved to be convergent under some reasonable assumptions. The numerical experiment shows the effectiveness of the algorithm.

Introduction and Objectives: We initiated this multicenter study to integrate important risk factors to create a nomogram for hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) for clinician decision-making. Patients and Methods: Between April 2011 and March 2022, 2281 HCC patients with an HBV-related diagnosis were included. All patients were randomly divided into two groups in a ratio of 7:3 (training cohort, n = 1597; validation cohort, n = 684). The nomogram was built in the training cohort via Cox regression model and validated in the validation cohort. Results: Multivariate Cox analyses revealed that the portal vein tumor thrombus, Child–Pugh class, tumor diameter, alanine aminotransferase level, tumor number, extrahepatic metastases, and therapy were independent predictive variables impacting overall survival. We constructed a new nomogram to predict 1-, 2-, and 3-year survival rates based on these factors. The nomogram-related receiver operating characteristics (ROC) curves indicated that the area under the curve (AUC) values were 0.809, 0.806, and 0.764 in predicting 1-, 2-, and 3-year survival rates, respectively. Furthermore, the calibration curves revealed good agreement between real measurements and nomogram predictions. The decision curve analyses (DCA) curves demonstrated excellent therapeutic application potential. In addition, stratified by risk scores, low-risk groups had longer median OS than medium–high-risk groups (p < 0.001). Conclusions: The nomogram we constructed showed good performance in predicting the 1-year survival rate for HBV- related HCC.

ObjectiveTo examine trends in patient and visitor violence (PVV) among large public hospitals from 2016 to 2020 in China, and investigate the effects of infection prevention and control (IPC) measures on PVV during the COVID-19 pandemic.MethodsThe hospital-level data of PVV used in this study from 2016 to 2020 in three cities in northern China were extracted from the database of the Medical Quality and Safety Notification System from 41 public hospitals. The difference-in-difference (DID) method was used to estimate the effects of IPC measures on PVV. The empirical strategy was to compare changes in the incidence rate of PVV in public hospitals where IPC measures were stricter to relatively weaker hospitals.ResultsFrom 2019 to 2020, the incidence rate of PVV decreases from 4.59 to 2.15% for high-IPC measure level hospitals and increases from 4.42 to 4.56% for medium-IPC measure level hospitals. The results from the DID models showed that as the IPC measure level increased, the incidence rate of PVV (β = −3.12, 95% CI = −5.74 ~ −0.50) decreased more significantly based on controlling for hospital fixed effects and time trends.ConclusionThe multi-dimensional and comprehensive IPC measures throughout the pandemic in China have not only controlled the pandemic, but also directly or indirectly reduced the incidence rate of PVV by alleviating the stress of health workers and the crowded working environment, creating a good order of admission, and reducing patient waiting time.

In this study, nitrogen-doped carbon dots (N-CDs) with excellent peroxidase-like activity were prepared using locust powder as the carbon source by a self-exothermic reaction. The obtained N-CDs could catalyze the oxidation of the chromogenic substrate 3,3′,5,5′-tetramethylbenzidine (TMB) in the presence of H2O2 to generate a blue oxidized product (TMBox) with a maximum absorption peak at 654 nm. The catalytic reaction conditions were optimized; furthermore, steady-state kinetic analysis indicated that N-CDs exhibited high affinity toward both TMB and H2O2, and the Michaelis-Menten constant (km) values were 0.115 mM (TMB) and 0.764 mM (H2O2). A smartphone-based colorimetric method was developed for quantitative detection. The 1/L values (L stands for lightness in HSL color space) of the TMBox solution were recorded via an iPhone application Color Analyzer. Since H2O2 is the by-product of glucose (Glu) oxidation in the presence of glucose oxidase (GOx), a simple, sensitive, and selective smartphone-based colorimetric method was developed for the determination of Glu, and the detection limit was 1.09 μM. The smartphone-based method was successfully applied to determine Glu in different food samples with recoveries in the range of 88.5–109.0 %.

The role(s) of nuclear factor erythroid 2-related factor 2 (NRF2) in diabetic kidney disease (DKD) is/are controversial. We hypothesized that Nrf2 deficiency in type 2 diabetes (T2D) db/db mice (db/dbNrf2 knockout (KO)) attenuates DKD progression through the down-regulation of angiotensinogen (AGT), sodium-glucose cotransporter-2 (SGLT2), scavenger receptor CD36, and fatty -acid-binding protein 4 (FABP4), and lipid accumulation in renal proximal tubular cells (RPTCs). Db/dbNrf2 KO mice were studied at 16 weeks of age. Human RPTCs (HK2) with NRF2 KO via CRISPR-Cas9 genome editing and kidneys from patients with or without T2D were examined. Compared with db/db mice, db/dbNrf2 KO mice had lower systolic blood pressure, fasting blood glucose, kidney hypertrophy, glomerular filtration rate, urinary albumin/creatinine ratio, tubular lipid droplet accumulation, and decreased expression of AGT, SGLT2, CD36, and FABP4 in RPTCs. Male and female mice had similar results. NRF2 KO attenuated the stimulatory effect of the Nrf2 activator, oltipraz, on AGT, SGLT2, and CD36 expression and high-glucose/free fatty acid (FFA)-stimulated lipid accumulation in HK2. Kidneys from T2D patients exhibited markedly higher levels of CD36 and FABP4 in RPTCs than kidneys from non-diabetic patients. These data suggest that NRF2 exacerbates DKD through the stimulation of AGT, SGLT2, CD36, and FABP4 expression and lipid accumulation in RPTCs of T2D.

BackgroundGlioblastoma multiforme (GBM) is the most common cancer of the central nervous system, while Parkinson’s disease (PD) is a degenerative neurological condition frequently affecting the elderly. Neurotrophic factors are key factors associated with the progression of degenerative neuropathies and gliomas.MethodsThe 2601 neurotrophic factor-related genes (NFRGs) available in the Genecards portal were analyzed and 12 NFRGs with potential roles in the pathogenesis of Parkinson’s disease and the prognosis of GBM were identified. LASSO regression and random forest algorithms were then used to screen the key NFRGs. The correlation of the key NFRGs with immune pathways was verified using GSEA (Gene Set Enrichment Analysis). A prognostic risk scoring system was constructed using LASSO (Least absolute shrinkage and selection operator) and multivariate Cox risk regression based on the expression of the 12 NFRGs in the GBM cohort from The Cancer Genome Atlas (TCGA) database. We also investigated differences in clinical characteristics, mutational landscape, immune cell infiltration, and predicted efficacy of immunotherapy between risk groups. Finally, the accuracy of the model genes was validated using multi-omics mutation analysis, single-cell sequencing, QT-PCR, and HPA.ResultsWe found that 4 NFRGs were more reliable for the diagnosis of Parkinson’s disease through the use of machine learning techniques. These results were validated using two external cohorts. We also identified 7 NFRGs that were highly associated with the prognosis and diagnosis of GBM. Patients in the low-risk group had a greater overall survival (OS) than those in the high-risk group. The nomogram generated based on clinical characteristics and risk scores showed strong prognostic prediction ability. The NFRG signature was an independent prognostic predictor for GBM. The low-risk group was more likely to benefit from immunotherapy based on the degree of immune cell infiltration, expression of immune checkpoints (ICs), and predicted response to immunotherapy. In the end, 2 NFRGs (EN1 and LOXL1) were identified as crucial for the development of Parkinson’s disease and the outcome of GBM.ConclusionsOur study revealed that 4 NFRGs are involved in the progression of PD. The 7-NFRGs risk score model can predict the prognosis of GBM patients and help clinicians to classify the GBM patients into high and low risk groups. EN1, and LOXL1 can be used as therapeutic targets for personalized immunotherapy for patients with PD and GBM.

Background: Head and neck squamous cell carcinoma (HNSCC) is the seventh most common type of cancer worldwide. Its highly aggressive and heterogeneous nature and complex tumor microenvironment result in variable prognosis and immunotherapeutic outcomes for patients with HNSCC. Neurotrophic factor-related genes (NFRGs) play an essential role in the development of malignancies but have rarely been studied in HNSCC. The aim of this study was to develop a reliable prognostic model based on NFRGs for assessing the prognosis and immunotherapy of HNSCC patients and to provide guidance for clinical diagnosis and treatment.Methods: Based on the TCGA-HNSC cohort in the Cancer Genome Atlas (TCGA) database, expression profiles of NFRGs were obtained from 502 HNSCC samples and 44 normal samples, and the expression and prognosis of 2601 NFRGs were analyzed. TGCA-HNSC samples were randomly divided into training and test sets (7:3). GEO database of 97 tumor samples was used as the external validation set. One-way Cox regression analysis and Lasso Cox regression analysis were used to screen for differentially expressed genes significantly associated with prognosis. Based on 18 NFRGs, lasso and multivariate Cox proportional risk regression were used to construct a prognostic risk scoring system. ssGSEA was applied to analyze the immune status of patients in high- and low-risk groups.Results: The 18 NFRGs were considered to be closely associated with HNSCC prognosis and were good predictors of HNSCC. The multifactorial analysis found that the NFRGs signature was an independent prognostic factor for HNSCC, and patients in the low-risk group had higher overall survival (OS) than those in the high-risk group. The nomogram prediction map constructed from clinical characteristics and risk scores had good prognostic power. Patients in the low-risk group had higher levels of immune infiltration and expression of immune checkpoints and were more likely to benefit from immunotherapy.Conclusion: The NFRGs risk score model can well predict the prognosis of HNSCC patients. A nomogram based on this model can help clinicians classify HNSCC patients prognostically and identify specific subgroups of patients who may have better outcomes with immunotherapy and chemotherapy, and carry out personalized treatment for HNSCC patients.

BackgroundWhether intensity-modulated radiotherapy (IMRT) can enhance the efficacy of the programmed death (PD)-1 inhibitors combined with anti-angiogenic therapy for hepatocellular carcinoma (HCC) is unclear. Therefore, we conducted this multicenter retrospective study to investigate the efficacy of the combination of PD-1 inhibitors with anti-angiogenic therapy and IMRT.MethodsFrom April 2019 to March 2022, a total of 197 patients with HCC [combination of PD-1 inhibitors with anti-angiogenic therapy and IMRT (triple therapy group), 54; PD-1 inhibitors plus anti-angiogenic therapy (control group), 143] were included in our study. Propensity score matching (PSM) was applied to identify two groups with similar baselines. The objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) of the two groups were compared before and after matching.ResultsPrior to PSM, the triple therapy group had higher ORR (42.6% vs 24.5%, P = 0.013) and more superior median OS (mOS) (20.1 vs 13.3 months, P = 0.009) and median PFS (mPFS) (8.7 vs 5.4 months, P = 0.001) than the control group. Following PSM, the triple therapy group still exhibited better mPFS (8.7 vs 5.4 months, P = 0.013) and mOS (18.5 vs 12.6 months, P = 0.043) than the control group. However, the ORR of the two groups was similar (40% vs 25%, P = 0.152). No significant difference was observed in the treatment-related adverse events between the two groups (P < 0.05 for all). ConclusionsThe combination of PD-1 inhibitors with anti-angiogenic therapy and IMRT for HCC is a promising regimen.

AimA programmed death 1 (PD-1) inhibitor coupled with radiotherapy and antiangiogenic therapy is a potential therapeutic strategy for advanced hepatocellular carcinoma (HCC). We aimed to determine if circulating tumor cells (CTCs) positive for programmed death-ligand 1 (PD-L1) could be employed as a predictive biomarker in HCC patients receiving triple therapy.MethodsIn this study, HCC patients received a PD-1 inhibitor in combination with intensity-modulated radiotherapy (IMRT) and antiangiogenic therapy. Following IMRT, the PD-1 inhibitor was administrated once every 3 weeks, while the antiangiogenic drug was given once a day. Treatment was continued until the disease progressed. Two mL of peripheral blood was collected at baseline, 1 month, and 3 months after treatment for CTC enrichment using the CytoSorter® system with a CytoSorter™ CTC PD-L1 Kit (Watson Biotech., China).ResultA total of 47 HCC patients receiving the triple therapy were enrolled in this study. Patients with < 2 PD-L1+ CTCs at baseline had a higher objective response rate (ORR) and longer overall survival (OS) than those with ≥ 2 PD-L1+ CTCs (56.5% vs. 16.7%, p = 0.007; not reach vs. 10.8 months, p = 0.001, respectively). The count of PD-L1+ CTCs was found to be an independent predictive biomarker of OS. Furthermore, the objective response was more likely to be achieved in patients with a dynamic decrease in PD-L1+ CTC counts at 1 month after treatment.ConclusionsOur study demonstrated that PD-L1+ CTCs could be a predictive biomarker for HCC patients receiving PD-1 inhibitors in combination with IMRT and antiangiogenic therapy.

Introduction and Objectives: Both external radiotherapy and sorafenib are promising treatments for hepatocellular carcinoma (HCC). Nevertheless, the combined treatment of external radiotherapy and sorafenib has not been widely applied clinically due to potentially adverse effects. This meta-analysis aimed to evaluate the clinical efficacy and safety of external radiotherapy combined with sorafenib in the treatment of HCC. Methods: Pubmed, MEDLINE, EMBASE, Cochrane Library, and Web of Science databases were searched. The primary and secondary observation endpoints were the end of survival and incidence of adverse events, respectively. 11 studies involving 664 patients were included in this meta-analysis. Results: The results demonstrated that median overall survival (mOS) and median progression-free survival (mPFS) of the external radiotherapy combined with sorafenib (RS) group were 19.45 months and 8.20 months. The one- and two-year survival rates were 0.65 (95%CI: 0.55–0.76) and 0.40 (95%CI: 0.24–0.56). The incidence of adverse events was 0.34 (95%CI: 0.25–0.44). Conclusions: The findings demonstrated that the survival of the RS group was significantly improved and few severe adverse events were observed. Hence, it can be concluded that external radiotherapy combined with sorafenib is a safe, effective, and promising therapeutic option for HCC.

Phosphors with apatite structure have shown potential applications in solid-state lighting and display industry due to their flexible crystal structure, controllable chemical composition and different crystallographic positions of single doped or co-doped RE ions. The study of natural luminescent apatites play an important role in the development of new apatite phosphors. In this paper, we reviewed the recent progress in the study of apatite phosphors, including our study of some natural apatites and enlightenment gained, research progress in single-doped apatite structure luminescent materials, color tunable single doped apatite luminescent materials, color tuning through energy transfer and density functional theory calculation in apatite-type phosphor study. Our purpose is to demonstrate the way of developing phosphors of natural luminescent minerals. Based on the current progress, we put forward the research prospects of apatite phosphors.

Bilateral investment agreements are bilateral treaties between capital exporting countries and host countries, which is specially used to protect international investment, and the contract execution is directly related to the daily operation of multinational enterprises. Based on the panel data of 73 developing countries from 2005 to 2019, this paper examines the improvement effect of BITs on the contract execution of host countries. The study found that both the overall bilateral investment agreements and the bilateral investment agreements in force can significantly improve the contract execution of the host country. Due to the differences between the civil law system and the common law system in many aspects, such as the source of evidence and trial mode, the effect of BITs on the improvement of contract execution in host countries of the common law system is more prominent. In terms of specific impact, the improvement effect of BITs on time is significantly better than cost. The core conclusion is still valid after changing the estimation method and eliminating abnormal samples.

Abstract Nowadays, China BeiDou Navigation Satellite System (BDS) has been developed well and provided global services with highly precise positioning, navigation and timing (PNT) as well as unique short-message communication, particularly global system (BDS-3) with higher precision multi-frequency signals. The precise point positioning (PPP) can provide the precise position, receiver clock, and zenith tropospheric delay (ZTD) with a stand-alone receiver compared to the traditional double differenced relative positioning mode, which has been widely used in PNT, geodesy, meteorology and so on. However, it has a lot of challenges for multi-frequency BDS PPP with different strategies and more unknown parameters. In this paper, the detailed PPP models using the single-, dual-, triple-, and quad-frequency BDS observations are presented and evaluated. Firstly, BDS system and PPP method are introduced. Secondly, the stochastic models of time delay bias in BDS-2/BDS-3 PPP including the neglection, random constant, random walk and white noise are presented. Then, three single-frequency, four dual-frequency, four triple-frequency and four quad-frequency BDS PPP models are provided. Finally, the BDS PPP models progress and performances including theoretical comparison of the models, positioning performances, precise time and frequency transfer, ZTD, inter-frequency bias (IFB) and differential code bias (DCB) are presented and evaluated as well as future challenges. The results show that the multi-frequency BDS observations will greatly improve the PPP performances.

Global Navigation Satellite System (GNSS) is recognized as an effective tool to retrieve high-precision seismic displacements, which has been widely used in earthquake early warning systems such as magnitude estimation and fault slip inversion. In this study, we present two multi-GNSS positioning models for rapidly capturing real-time coseismic displacements using the raw pseudorange, carrier phase and Doppler measurements, called constant velocity (CV) and constant acceleration (CA) dynamic precise point positioning (PPP) models, respectively. The proposed methods are validated with the datasets collected during the 2019 July 4 Mw 6.4 and July 6 Mw 7.1 earthquakes in real-time scenarios. Results show that the two models can provide accurate displacement waveforms with the accuracy of few centimeters. Besides, the multi-GNSS integration can significantly improve the model performances compared with GPS-only solutions in both time- and frequency- domains. The dynamic PPP models can also reliably recover the moment magnitudes and permanent seismic displacements, indicating that the methods have the potential to benefit for earthquake early warning and rapid geohazard assessment.

The maturity and commercialization of emerging digital technologies represented by artificial intelligence, cloud computing, block chain and virtual reality are giving birth to a new and higher economic form, that is, digital economy. Digital economy is different from the traditional industrial economy. It is clean, efficient, green and recyclable. It represents and promotes the future direction of global economic development, especially in the context of the sudden COVID-19 pandemic as a continuing disaster. Therefore, it is essential to establish the comprehensive evaluation model of digital economy development scientifically and reasonably. In this paper, first on the basis of literature analysis, the relevant indicators of digital economy development are collected manually and then screened by the grey dynamic clustering and rough set reduction theory. The evaluation index system of digital economy development is constructed from four dimensions: digital innovation impetus support, digital infrastructure construction support, national economic environment and digital policy guarantee, digital integration and application. Next the subjective weight and objective weight are calculated by the group FAHP method, entropy method and improved CRITIC method, and the combined weight is integrated with the thought of maximum variance. The grey correlation analysis and improved VIKOR model are combined to systematically evaluate the digital economy development level of 31 provinces and cities in China from 2013 to 2019. The results of empirical analysis show that the overall development of China’s digital economy shows a trend of superposition and rise, and the development of digital economy in the four major economic zones is unbalanced. Finally, we put forward targeted opinions on the construction of China’s provincial digital economy.

Breast cancer lung metastasis has a high mortality rate and lacks effective treatments, for the factors that determine breast cancer lung metastasis are not yet well understood. In this study, data from 1067 primary tumors in four public datasets revealed the distinct microenvironments and immune composition among patients with or without lung metastasis. We used multi-omics data of the TCGA cohort to emphasize the following characteristics that may lead to lung metastasis: more aggressive tumor malignant behaviors, severer genomic instability, higher immunogenicity but showed generalized inhibition of effector functions of immune cells. Furthermore, we found that mast cell fraction can be used as an index for individual lung metastasis status prediction and verified in the 20 human breast cancer samples. The lower mast cell infiltrations correlated with tumors that were more malignant and prone to have lung metastasis. This study is the first comprehensive analysis of the molecular and cellular characteristics and mutation profiles of breast cancer lung metastasis, which may be applicable for prognostic prediction and aid in choosing appropriate medical examinations and therapeutic regimens.

BackgroundLynch syndrome is an autosomal dominant disorder associated with a high incidence of various cancer types. Multiple variants of mismatch repair genes have been reported for Lynch syndrome. However, the diagnosis in patients with atypical cancer types remains challenging. Specifically, little is known about the genetic background of Lynch syndrome-related renal carcinoma. We present a case wherein a renal carcinoma patient with multiple primary skin tumors harbored a variant that has not been previously shown to be associated with Lynch syndrome.Case PresentationThe proband was a 60-year-old Chinese man with a history of Lynch syndrome-related renal carcinoma and recurrent primary skin tumors. Immunohistochemistry revealed loss of MSH2 and MSH6. Sequencing of mismatch repair genes revealed a previously unknown germline MSH2 mutation (c.1024_1026), which results in an amino acid deletion (p.V342). This variant was co-segregated among the carcinoma-affected family members. After six cycles of immunotherapy, a marked regression of the skin tumors was observed.ConclusionsWe clarify the pathogenic significance of this newly described mutation and suggest immunotherapy for patients with this subtype of Lynch syndrome.

Angiogenesis is an essential physiological process and hallmark of cancer. Currently, antiangiogenic therapy, mostly targeting the vascular endothelial growth factor (VEGF)/VEGFR2 signaling axis, is commonly used in the clinic for solid tumors. However, antiangiogenic therapies for breast cancer patients have produced limited survival benefits since cancer cells rapidly resistant to anti-VEGFR2 therapy. We applied the low-dose and high-dose VEGFR2 mAb or VEGFR2-tyrosine kinase inhibitor (TKI) agents in multiple breast cancer mouse models and found that low-dose VEGFR2 mAb or VEGFR2-TKI achieved good effects in controlling cancer progression, while high-dose treatment was not effective. To further investigate the mechanism involved in regulating the drug resistance, we found that high-dose anti-VEGFR2 treatment elicited IL17A expression in γδ T cells via VEGFR1-PI3K-AKT pathway activation and then promoted N2-like neutrophil polarization, thus inducing CD8+ T cell exhaustion to shape an immunosuppressive microenvironment. Combining anti-VEGFR2 therapy with immunotherapy such as IL17A, PD-1 or Ly-6G mAb therapy, which targeting the immunomodulatory axis of “γδT17 cells-N2 neutrophils” in vivo, showed promising therapeutic effects in breast cancer treatment. This study illustrates the potential mechanism of antiangiogenic therapy resistance in breast cancer and provides synergy treatment for cancer.

From genre to interdisciplinary and trans-medial artistic practice, “autotheory” has attracted great attention for formally distilling a troublesome contradiction of dualistic opposition between theory and practice in arts and attempting to solve it. In this paper, autotheory is understood as the joining of reflective thinking through the “collective self” and the reflective thinking of “theory”. Based on Lauren Fournier’s research, this paper investigates two kinds of art practices in contemporary Chinese art. The first developed from the art movements of the late 1970s to the late 1980s, when there was a rethinking of collective selfhood in Chinese art circles. This “collective self” in Chinese culture expands the parameters of autotheory’s individualized, autobiographical “self”, as described by Fournier. The second example of autotheory discussed in this paper explores contemporary Chinese feminist art. Due to its cultural background and historical trajectory, different dimensions of individualized autotheoretical practices have developed in feminist contemporary art in China in the new era. The case studies presented in this paper show the flexibility of autotheory as a methodology, the complex conditions it applies to, and the potential to generate theory from expanded notions of “self” in art practice.

Abstract Background This study aims to carry out the vitrification freezing of a large ovarian tissue in the human body, and evaluate its feasibility. Results A total of 18 ovarian tissues in the human body were selected, and each tissue was cut into three large ovarian cortex slices. These tissues were randomly divided into three groups: vitrification freezing group (group A), programmed freezing group (group B), and fresh control group (group C). Then, the morphological analysis and apoptosis detection of each ovarian tissue was carried out, followed by the recycling of ovarian tissues at three weeks after the heterotransplantation of nude mice, in order to detect the follicle preservation conditions. The immunohistochemistory method was applied to detect the follicle activity. In comparing the proportion of primordial follicle with normal morphology after unfreezing between group A and group B, the difference was not statistically significant (P > 0.05). Furthermore, the incidence of follicle apoptosis in group A and group B was higher than that in the group C (P 0.05). The interstitial cell apoptosis rate in group A was lower than that of the group B, showing that the difference was statistically significant (P

Abstract Background Interleukin-17 (IL-17), a pleiotropic cytokine, plays a significant role in the inflammatory diseases. By a pilot study with small population, IL-17 polymorphisms (IL-17A rs2275913 and IL-17F rs763780) showed a more potential risk factor in knee osteoarthritis (OA) in our recruited subjects. In the current study, the association between IL-17A rs2275913 and IL-17F rs763780and the risk of OA in a Chinese population is studied. Methods The IL-17A rs2275913 and IL-17F rs763780 polymorphisms were determined in 594 knee OA cases and 576 healthy controls, using polymerase chain reaction-restriction fragment length polymorphism assay. The relationship between genotype distribution and disease risk, as well as OA severity was analyzed by Chi-square test and multivariate logistic regression. Results The experimental results indicated that the polymorphism in IL-17 gene rs2275913 site were related to knee OA risk after the adjustment of BMI, sex, age, smoking and drinking status (AA vs. GG: odds ratio (OR), 1.411; 95% confidence interval (CI), 1.021–1.950; P = 0.040; A allele vs. G allele: OR, 1.192; P = 0.037; 95% CI, 1.012–1.404;). Similarly, subjects who are bearing the rs763780 variant genotypes (TC and CC) and C allele also had a higher susceptibility to knee OA compared with those who are bearing the TT genotype (TC vs. TT, OR: 1.312; P = 0.039; 95% CI: 1.017–1.692; CC vs. TT, OR: 2.812, P = 0.006, 95% CI: 1.338–5.909; C allele Vs. T allele, OR:1.413, P = 0.002, 95% CI:1.141–1.751). In the meantime, one high-risk haplotypes, AC (OR was 7.22, P

Based on the data of 812 small towns in Chongqing, China, this paper attempts to conduct an empirical analysis on whether tourist towns with excellent natural environment, policy advantage, and market preference are more ecologically livable than ordinary small towns. It is found that as a whole, tourist towns are indeed more ecologically livable than ordinary small towns. Also, from the perspective of grading, both the national and provincial tourist towns have the advantage of ecological livability, but the advantage of national ones is more prominent. Furthermore, the ecological livability of tourist towns is affected by location advantage and policy inclination. The implications of the results are discussed following the outcomes of the coronavirus disease 2019 outbreak. The suggestions beyond the coronavirus disease 2019 are also provided.

Whitlockite has the advantages of a low sintering temperature, high stability, and a low fabrication cost, and it is widely used as the host for luminescent material. In this study, Ca1.8Li0.6La0.6−x(PO4)2:xDy3+ phosphor was prepared by the high-temperature solid-state method, and its structure, composition, and luminescence properties were systematically studied. The results showed that a new whitlockite type matrix was prepared by replacing Ca2+ in whitlockite with monovalent and trivalent cations. The prepared phosphors belonged to a hexagonal crystal system with a particle size in the range of 5–20 μm. Under the excitation of 350 nm UV light, the samples emitted white light, and there were mainly two stronger emission peaks at 481 nm in the blue band and 573 nm in the yellow band, which correspond to the electron transitions at 4F9/2→6H15/2 and 4F9/2→6H13/2 of Dy3+, respectively. The optimal doping concentration of Dy3+ in Ca1.8Li0.6La0.6(PO4)2 matrix was 0.03 (mol%). The main mechanism of concentration quenching in the sample was dipole–dipole energy transfer. When the temperature was 130 °C, the luminescence intensity of the samples was 78.7% of that at 30 °C, and their thermal quenching activation energy was 0.25 eV. The CIE coordinates of the sample at 30 °C were (0.2750, 0.3006), and their luminescent colors do not change with temperature. All the results indicate that Ca1.8Li0.6La0.6−x(PO4)2:xDy3+ phosphor is a luminescent material with good luminescence performance and thermal stability, which shows a promising application in the field of LED display.

Global Navigation Satellite Systems (GNSSs) can provide high-precision positioning services, which can be applied to fields including navigation and positioning, autonomous driving, unmanned aerial vehicles and so on. However, GNSS signals are easily disrupted in complex environments, which results in a positioning performance with a significantly inferior accuracy and lengthier convergence time, particularly for the single GNSS system. In this paper, multi-GNSS precise point positioning (PPP) with tightly integrating ultra-wide band (UWB) technology is presented to implement fast and precise navigation and positioning. The validity of the algorithm is evaluated by a set of GNSS and UWB data. The statistics indicate that multi-GNSS/UWB integration can significantly improve positioning performance in terms of the positioning accuracy and convergence time. The improvement of the positioning performance for the GNSS/UWB tightly coupled integration mainly concerns the north and east directions, and to a lesser extent, the vertical direction. Furthermore, the convergence performance of GNSS/UWB solution is analyzed by simulating GNSS signal interruption. The reliability and robustness of GNSS/UWB solution during GNSS signal interruption is verified. The results show that multi-GNSS/UWB solution can significantly improve the accuracy and convergence speed of PPP.

Lung metastasis is one of the leading causes of death in patients with breast cancer. The mechanism of tumor metastasis remains controversial. Recently, the formation of a pre-metastatic niche has been considered a key factor contributing to breast cancer metastasis, which might also explain the tendency of organ metastasis. Our study initially re-examined the critical time of the niche formation and simultaneously detected a novel subset of neutrophils, CD62Ldim neutrophils, which had not previously been reported in tumor metastasis; the number of these cells progressively increased during breast cancer progression and was closely related to the formation of the pre-metastatic niche. Furthermore, we explored the mechanism of their aggregation in the pre-metastatic niche in the lung and found that they were specifically chemoattracted by the CXCL12-CXCR4 signaling pathway. Compared to the CD62Lhi neutrophils, CD62Ldim neutrophils exhibited stronger adhesion and increased survival. The results provide new insights into the subsequent targeted treatment of breast cancer metastasis.

Visual reasoning is a critical stage in visual question answering (Antol et al., 2015), but most of the state-of-the-art methods categorized the VQA tasks as a classification problem without taking the reasoning process into account. Various approaches are proposed to solve this multi-modal task that requires both abilities of comprehension and reasoning. The recently proposed neural module network (Andreas et al., 2016b), which assembles the model with a few primitive modules, is capable of performing a spatial or arithmetical reasoning over the input image to answer the questions. Nevertheless, its performance is not satisfying especially in the real-world datasets (e.g., VQA 1.0& 2.0) due to its limited primitive modules and suboptimal layout. To address these issues, we propose a novel method of Dual-Path Neural Module Network which can implement complex visual reasoning by forming a more flexible layout regularized by the pairwise loss. Specifically, we first use the region proposal network to generate both visual and spatial information, which helps it perform spatial reasoning. Then, we advocate to process a pair of different images along with the same question simultaneously, named as a “complementary pair,” which encourages the model to learn a more reasonable layout by suppressing the overfitting to the language priors. The model can jointly learn the parameters in the primitive module and the layout generation policy, which is further boosted by introducing a novel pairwise reward. Extensive experiments show that our approach significantly improves the performance of neural module networks especially on the real-world datasets.

Abstract Background Lung ultrasound and echocardiography are mainly applied in critical care and emergency medicine. However, the diagnostic value of cardiopulmonary ultrasound in elderly patients with acute respiratory distress syndrome (ARDS) is still unclear. Methods Consecutive patients admitted to ICU with the diagnosis of suspected ARDS based on clinical grounds were enrolled. Cardiopulmonary ultrasound was performed as part of monitoring on day 1, day 2 and day 3. On each day a bedside ultrasound was performed to examine the lungs and calculate the Left Ventricular Ejection Fraction (LVEF). On day 3, a thoracic CT was performed on each patient as gold standard for ARDS imaging diagnosis. According to the results from CT scan, patients were grouped into ARDS group or Non-ARDS group. The relation between the cardiopulmonary ultrasound results on each day and the results of CT scan was analyzed. Results Fifty one consecutive patients aged from 73 to 97 years old were enrolled. Based on CT criteria, 33 patients were classified into the ARDS group, while 18 patients were included in non-ARDS group. There was no significant difference between the two groups in baseline characteristics, including gender, age, underlying disease, comorbidities, APACHE II score, SOFA score, and PaO2/FiO2 ratio (P > 0.05). Lung ultrasound (LUS) examination results were consistent with the CT scan results in diagnosis of pulmonary lesions. The Kappa values were 0.55, 0.74 and 0.82 on day 1, day 2 and day 3, respectively. The ROC analysis showed that the sensitivity, specificity and area under curve of ROC (AUROC) for lung ultrasound in diagnose ARDS were 0.788,0.778,0.783;0.909,0.833,0.871;0.970,0.833,0.902 on day 1, day 2 and day 3, respectively. However, cardiopulmonary ultrasound performed better in diagnosing ARDS in elderly patients. The sensitivity, specificity and AUROC were 0.879,0.889,0.924;0.939,0.889,0.961;and 0.970,0.833,0.956 on day 1, day 2 and day 3, respectively. The combined performances of cardiopulmonary ultrasound, N-terminal pro-brain natriuretic peptide (NT-proBNP), and PaO2/FiO2 ratio improved the specificity of the diagnosis of ARDS in elderly patients. Conclusions LUS examination results were consistent with the CT scan results in diagnosis of pulmonary lesions. Cardiopulmonary ultrasound has a greater diagnostic accuracy in elderly patients with ARDS, compared with LUS alone. The combined performances of cardiopulmonary ultrasound, NT-proBNP, and PaO2/FiO2 increased the specificity of the diagnosis of ARDS in elderly patients.

Along with the blowout of new applications and the integration of the heterogeneous networks platforms in the future Internet of everything, the self-management of virtual radio access network is of significant importance. The urgent problem needed to be solved for the self-management in virtual radio access network is the match of application and virtual service (tailored service of virtual functions for the application). In this paper, an identification decision tree learning model (IDTLM) based on transfer learning has been proposed. First, we do research on the redundant problem of the traditional packet decision trees and reduce the dimensionality of features by a proximal gradient descent method and clustering the features by Lagrange's multiplier, so as to improve the online matching speed between applications and virtual service. And then, in consideration of the independent and non-identical distribution among online and trained data, and the possible change of virtualized network platform, a method of transfer learning is proposed to improve the quality of generalization for IDTLM. Finally, online test is done for IDTLM, and the result shows that the accuracy rate of trained applications can reach 99% and the accuracy rate can reach 96% if untrained applications are included. Meanwhile, theoretical analysis has been carried out for the transfer of IDTLM. The analysis shows that IDTLM system is of high recognizing speed and low false positive rate and it could adapt to the transfer of different scenarios.

Global Navigation Satellite System (GNSS) Precise Point Positioning (PPP) enables the estimation the ionospheric vertical total electron content (VTEC) as well as the by-product of the satellite Pseudorange observable-specific signal bias (OSB). The single-frequency PPP models, with the ionosphere-float and ionosphere-free approaches in ionospheric studies, have recently been discussed by the authors. However, the multi-frequency observations can improve the performances of the ionospheric research compared with the single-frequency approaches. This paper presents three dual-frequency PPP approaches using the BeiDou Navigation Satellite System (BDS) B1I/B3I observations to investigate ionospheric activities. Datasets collected from the globally distributed stations are used to evaluate the performance of the ionospheric modeling with the ionospheric single- and multi-layer mapping functions (MFs), respectively. The characteristics of the estimated ionospheric VTEC and BDS satellite pseudorange OSB are both analyzed. The results indicated that the three dual-frequency PPP models could all be applied to the ionospheric studies, among which the dual-frequency ionosphere-float PPP model exhibits the best performance. The three dual-frequency PPP models all possess the capacity for ionospheric applications in the GNSS community.

Context: Codeine, also known as 3-methylmorphine, is an opiate used to treat pain, as a cough medicine and for diarrhoea. No study on the effects of codeine on the metabolic capacity of CYP enzyme is reported. Objective: In order to investigate the effects of codeine on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of CYP2B1, CYP2D1, CYP1A2, CYP3A2 and CYP2C11. Materials and methods: Sprague–Dawley rats were randomly divided into codeine group (low, medium, high) and control group. The codeine group rats were given 4, 8, 16 mg/kg (low, medium, high) codeine by continuous intragastric administration for 14 days. Five probe drugs bupropion, metroprolol, phenacetin, midazolam and tolbutamide were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. Results and conclusion: The pharmacokinetic parameters of bupropion and metroprolol experienced obvious change with AUC(0-t), Cmax increased and CL decreased for bupropion in medium dosage group and midazolam low dosage group. This result indicates that the 14 day-intragastric administration of codeine may inhibit the metabolism of bupropion (CYP2B1) and midazolam (CYP3A2) in rat. Additional, there are no statistical differences for albumin (ALB), alkaline phosphatase (ALP), creatinine (Cr) after 14 intragastric administration of codeine, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid (UA) increased compared to control group. The biomedical test results show continuous 14 day-intragastric administration of codeine would cause liver damage.

Background: Thiazide diuretics may improve bone mineral density. However, results are inconsistent for studies evaluating the association between thiazides and risk of osteoporotic fracture. We performed an updated meta-analysis of cohort studies to determine the association between thiazides use and fracture risk.Methods: Relevant studies were identified via systematic search of PubMed and Embase. A random-effect model was used for meta-analysis. Subgroup analyses were performed to explore the potential influences of study characteristics on the outcome.Results: Seventeen cohort studies with 3,537,504 participants were included. The pooled results showed that use of thiazide diuretics at baseline did not significantly affect the risk of overall osteoporotic fracture incidence as compared with controls (risk ratio [RR]: 0.96, 95% confidence interval [CI]: 0.83 to 1.09, p = 0.51) with significant heterogeneity (p for Cochrane’s Q test < 0.001, I2 = 90%). Results of subgroup analyses indicated that general status of the participants may be an important determinant for the association between thiazide diuretics and subsequent risk of osteoporotic fracture. Use of thiazide diuretics was associated with significantly reduced risk of fracture in patients with acute status including new-onset stroke or spinal cord injury (RR: 0.70, 95% CI: 0.57 to 0.86, p < 0.001), but not in those with good conditions such as community-dwelling population or hypertensive patients (p for subgroup difference = 0.02).Conclusions: Use of thiazide diuretics is not associated with significantly affected risk of overall osteoporotic fracture. However, the association may be different according to the general status of the participants.

[This corrects the article DOI: 10.1371/journal.pone.0187886.].