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Abstract Background Cardiac iron overload and ferroptosis greatly contribute to the poor prognosis of myocardial infarction (MI). Iron chelator is one of the most promising strategies for scavenging excessive iron and alleviating cardiac dysfunction post MI. However, various side effects of existing chemical iron chelators restrict their clinical application, which calls for a more viable and safer approach to protect against iron injury in ischemic hearts. Results In this study, we isolated macrophage-derived extracellular vesicles (EVs) and identified macrophage-derived EVs as a novel endogenous biological chelator for iron. The administration of macrophage-derived EVs effectively reduced iron overload in hypoxia-treated cardiomyocytes and hearts post MI. Moreover, the oxidative stress and ferroptosis induced by excessive iron were considerably suppressed by application of macrophage-derived EVs. Mechanistically, transferrin receptor (TfR), which was inherited from macrophage to the surface of EVs, endowed EVs with the ability to bind to transferrin and remove excess protein-bound iron. EVs with TfR deficiency exhibited a loss of function in preventing MI-induced iron overload and protecting the heart from MI injury. Furthermore, the iron-chelating EVs were ultimately captured and processed by macrophages in the liver. Conclusions These results highlight the potential of macrophage-derived EVs as a powerful endogenous candidate for iron chelation therapy, offering a novel and promising therapeutic approach to protect against iron overload-induced injury in MI and other cardiovascular diseases.

Abstract Background Safely implementing transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD) requires accurate navigation. Traditional fluoroscopy falls short in reducing the risk of post-procedure pneumothorax. The potential of electromagnetic navigation bronchoscopy (ENB) as a more precise navigation method warrants further exploration. Methods A prospective cohort study was conducted on ILD patients undergoing TBLC. Patients were assigned either fluoroscopy or ENB for cryoprobe positioning. Navigation accuracy was evaluated using cone beam computed tomography (CBCT) images as the standard. Safety and diagnostic yield were also observed. Results Seventeen patients underwent TBLC, with 10 guided by fluoroscopy and seven by ENB. Fluoroscopy-guided cryoprobe navigation required more adjustments [9/15 (60%) v.s. 1/9 (11%), p = 0.018] for subsequent TBLC compared to ENB, as confirmed by CBCT images. Clinical characteristics, post-procedure complications, and biopsy specimen size showed no significant differences between the groups. Fourteen patients obtained a pathological diagnosis, and 15 received a multidisciplinary discussion (MDD) diagnosis. In the fluoroscopy group, three patients failed to obtain a pathological diagnosis, and two failed to obtain an MDD diagnosis. Conclusions ENB demonstrates significantly superior accuracy in TBLC navigation compared to traditional fluoroscopy when CBCT images are used as a reference. Further studies are necessary to determine the value of ENB in TBLC navigation for ILD patients.

Abstract Objective To assess lung deformation in patients with idiopathic pulmonary fibrosis (IPF) using with elastic registration algorithm applied to three-dimensional ultrashort echo time (3D-UTE) MRI and analyze relationship of lung deformation with the severity of IPF. Methods Seventy-six patients with IPF (mean age: 62 ± 6 years) and 62 age- and gender-matched healthy controls (mean age: 58 ± 4 years) were prospectively enrolled. End-inspiration and end-expiration images acquired with a single breath-hold 3D-UTE sequence were registered using elastic registration algorithm. Jacobian determinants were calculated from deformation fields and represented on color maps. Jac-mean (absolute value of the log means of Jacobian determinants) and the Dice similarity coefficient (Dice) were compared between different groups. Results Compared with healthy controls, the Jac-mean of IPF patients significantly decreased (0.21 ± 0.08 vs. 0.27 ± 0. 07, p < 0.001). Furthermore, the Jac-mean and Dice correlated with the metrics of pulmonary function tests and the composite physiological index. The lung deformation in IPF patients with dyspnea Medical Research Council (MRC) ≥ 3 (Jac-mean: 0.16 ± 0.03; Dice: 0.06 ± 0.02) was significantly lower than MRC1 (Jac-mean: 0. 25 ± 0.03, p < 0.001; Dice: 0.10 ± 0.01, p < 0.001) and MRC 2 (Jac-mean: 0.22 ± 0.11, p = 0.001; Dice: 0.08 ± 0.03, p = 0.006). Meanwhile, Jac-mean and Dice correlated with health-related quality of life, 6 min-walk distance, and the extent of pulmonary fibrosis. Jac-mean correlated with pulmonary vascular-related indexes on high-resolution CT. Conclusion The decreased lung deformation in IPF patients correlated with the clinical severity of IPF patients. Elastic registration of inspiratory-to-expiratory 3D UTE MRI may be a new morphological and functional marker for non-radiation and noninvasive evaluation of IPF. Critical relevance statement This prospective study demonstrated that lung deformation decreased in idiopathic pulmonary fibrosis (IPF) patients and correlated with the severity of IPF. Elastic registration of inspiratory-to-expiratory three-dimensional ultrashort echo time (3D UTE) MRI may be a new morphological and functional marker for non-radiation and noninvasive evaluation of IPF. Key points • Elastic registration of inspiratory-to-expiratory three-dimensional ultrashort echo time (3D UTE) MRI could evaluate lung deformation. • Lung deformation significantly decreased in idiopathic pulmonary fibrosis (IPF) patients, compared with the healthy controls. • Reduced lung deformation of IPF patients correlated with worsened pulmonary function and the composite physiological index (CPI). Graphical Abstract

Abstract The heart primarily derives its energy through lipid oxidation. In cardiomyocytes, lipids are stored in lipid droplets (LDs) and are utilized in mitochondria, although the structural and functional connections between these two organelles remain largely unknown. In this study, visible evidence have presented indicating that a complex is formed at the mitochondria‐LD membrane contact (MLC) site, involving mitochondrion‐localized Mfn2 and LD‐localized Hsc70. This complex serves to tether mitochondria to LDs, facilitating the transfer of fatty acids (FAs) from LDs to mitochondria for β‐oxidation. Reduction of Mfn2 induced by lipid overload inhibits MLC, hinders FA transfer, and results in lipid accumulation. Restoring Mfn2 reinstates MLC, alleviating myocardial lipotoxicity under lipid overload conditions both in‐vivo and in‐vitro. Additionally, prolonged lipid overload induces Mfn2 degradation through the ubiquitin‐proteasome pathway, following Mfn2 acetylation at the K243 site. This leads to the transition from adaptive lipid utilization to maladaptive lipotoxicity. The experimental findings are supported by clinical data from patients with obesity and age‐matched non‐obese individuals. These translational results make a significant contribution to the molecular understanding of MLC in the heart, and offer new insights into its role in myocardial lipotoxicity.

Abstract. Background:. The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. Methods:. In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. Results:. A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age,

Collision accidents involving construction vehicles and workers frequently occur at construction sites. Computer vision (CV) technology presents an efficient solution for collision-risk pre-warning. However, CV-based methods are still relatively rare and need an enhancement of their performance. Therefore, a novel three-stage collision-risk pre-warning model for construction vehicles and workers is proposed in this paper. This model consists of an object-sensing module (OSM), a trajectory prediction module (TPM), and a collision-risk assessment module (CRAM). In the OSM, the YOLOv5 algorithm is applied to identify and locate construction vehicles and workers; meanwhile, the DeepSORT algorithm is applied to the real-time tracking of the construction vehicles and workers. As a result, the historical trajectories of vehicles and workers are sensed. The original coordinates of the data are transformed to common real-world coordinate systems for convenient subsequent data acquisition, comparison, and analysis. Subsequently, the data are provided to a second stage (TPM). In the TPM, the optimized transformer algorithm is used for a real-time trajectory prediction of the construction vehicles and workers. In this paper, we enhance the reliability of the general object detection and trajectory prediction methods in the construction environments. With the assistance afforded by the optimization of the model’s hyperparameters, the prediction horizon is extended, and this gives the workers more time to take preventive measures. Finally, the prediction module indicates the possible trajectories of the vehicles and workers in the future and provides these trajectories to the CRAM. In the CRAM, the worker’s collision-risk level is assessed by a multi-factor-based collision-risk assessment rule, which is innovatively proposed in the present work. The multi-factor-based assessment rule is quantitatively involved in three critical risk factors, i.e., velocity, hazardous zones, and proximity. Experiments are performed within two different construction site scenarios to evaluate the effectiveness of the collision-risk pre-warning model. The research results show that the proposed collision pre-warning model can accurately predict the collision-risk level of workers at construction sites, with good tracking and predicting effect and an efficient collision-risk pre-warning strategy. Compared to the classical models, such as social-GAN and social-LSTM, the transformer-based trajectory prediction model demonstrates a superior accuracy, with an average displacement error of 0.53 m on the construction sites. Additionally, the optimized transformer model is capable of predicting six additional time steps, which equates to approximately 1.8 s. The collision pre-warning model proposed in this paper can help improve the safety of construction vehicles and workers.

Rapid and accurate mapping of soil properties in farmlands is crucial for guiding agricultural production and maintaining food security. Traditional methods using spectral features from remote sensing prove valuable for estimating soil properties, but are restricted to short periods of bare soil occurrence within agricultural settings. Addressing the challenge of predicting soil properties under crop cover, this study proposed an improved soil modeling framework that integrates dynamic crop growth information with machine learning techniques. The methodology’s robustness was tested on six key soil properties in an agricultural region of China, including soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), dissolved organic carbon (DOC), dissolved organic nitrogen (DON), and pH. Four experimental scenarios were established to assess the impact of crop growth information, represented by the normalized difference vegetation index (NDVI) and phenological parameters. Specifically, Scenario I utilized only natural factors (terrain and climate data); Scenario II added phenological parameters based on Scenario I; Scenario III incorporated time-series NDVI based on Scenario I; and Scenario IV combined all variables (traditional natural factors and crop growth information). These were evaluated using three advanced machine learning models: random forest (RF), Cubist, and Extreme Gradient Boosting (XGBoost). Results demonstrated that incorporating phenological parameters and time-series NDVI significantly improved model accuracy, enhancing predictions by up to 36% over models using only natural factors. Moreover, although both are crop growth factors, the contribution of the time-series NDVI variable to model accuracy surpassed that of the phenological variable for most soil properties. Relative importance analysis suggested that the crop growth information, derived from time-series NDVI and phenology data, collectively explained 14–45% of the spatial variation in soil properties. This study highlights the significant benefits of integrating remote sensing-based crop growth factors into soil property inversion under crop-covered conditions, providing valuable insights for digital soil mapping.

Abstract Introduction The GAP model was widely used as a simple risk “screening” method for patients with idiopathic pulmonary fibrosis (IPF). Objectives We sought to validate the GAP model in Chinese patients with IPF to evaluate whether it can accurately predict the risk for mortality. Methods A total of 212 patients with IPF diagnosed at China‐Japan Friendship Hospital from 2015 to 2019 were enrolled. The latest follow‐up ended in September 2022. Cumulative mortality of each GAP stage was calculated and compared based on Fine‐Gray models for survival, and lung transplantation was treated as a competing risk. The performance of the model was evaluated in terms of both discrimination and calibration. Results The cumulative mortality in patients with GAP stage III was significantly higher than that in those with GAP stage I or II (Gray's test p

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The pseudo-spin symmetry (PSS) provides an important angle to understand nuclear microscopic structure and the novel phenomena found in unstable nuclei. The relativistic Hartree–Fock (RHF) theory, that takes the important degrees of freedom associated with the π-meson and ρ-tensor (ρ-T) couplings into account, provides an appropriate description of the PSS restoration in realistic nuclei, particularly for the pseudo-spin (PS) doublets with high angular momenta (l˜). The investigations of the PSS within the RHF theory are recalled in this paper by focusing on the effects of the Fock terms. Aiming at common artificial shell closures appearing in previous relativistic mean-field calculations, the mechanism responsible for the PSS restoration of high-l˜ orbits is stressed, revealing the manifestation of nuclear in-medium effects on the PSS, and thus, providing qualitative guidance on modeling the in-medium balance between nuclear attractions and repulsions. Moreover, the essential role played by the ρ-T coupling, that contributes mainly via the Fock terms, is introduced as combined with the relations between the PSS and various nuclear phenomena, including the shell structure and the evolution, novel halo and bubble-like phenomena, and the superheavy magicity. As the consequences of the nuclear force in complicated nuclear many-body systems, the PSS itself and the mechanism therein can not only deepen our understanding of nuclear microscopic structure and relevant phenomena, but also provide special insight into the nature of the nuclear force, which can further enrich our knowledge of nuclear physics.

Explaining the physiological and ecological effects of wheat population density can provide new research methods for field crop production. A three-year field trial under drill single-seed seeding was conducted, which used three different intra-row seed-seedling spacings to quantitatively analyze the density effect from three perspectives—population, individual plant, and single-stem panicle—at the winter wheat harvest. The results showed that year and density had significant effects on both the population and individual plant yield (p < 0.05), as well as on some yield components and biomass indicators. The interaction between planting density and annual climate was found only in the number of grains for both the entire population and individual plants. With the increase in planting density, the CI gradually increased, inhibiting the growth of individual plants and leading to a negative impact on monoculture wheat yield. The drill single-seed seeding method can provide a basic experiment condition for analyzing the density effect. The density effect of wheat populations originates from intraspecific competition, which mainly affects the growth of individual plants. Research based on the analysis of density effects from the perspectives of population, individual plants, and single-stem panicles can provide a methodological reference for precision agriculture.

Since the beginning of the new century, there has been a notable enhancement in China’s ecological environment quality (EEQ), a development occurring in tandem with climate change and the extensive ecological restoration projects (ERPs) undertaken in the country. However, comprehensive insights into the spatial and temporal characteristics of China’s EEQ, and its responses to both climate change and human activities over the past two decades, have remained largely elusive. In this study, we harnessed a combination of multi-source remote-sensing data and reanalysis data. We employed Theil–Sen median trend analysis, multivariate regression residual analysis, and the Hurst index to examine the impacts and changing patterns of climatic factors and human activities on China’s EEQ during the past two decades. Furthermore, we endeavored to forecast the future trajectory of EEQ. Our findings underscore a significant improvement in EEQ across most regions of China between 2002 and 2019, with the most pronounced enhancements observed in the Loess Plateau, Northeast China, and South China. This transformation can be attributed to the combined influence of climatic factors and human activities, which jointly accounted for alterations in EEQ across 78.25% of China’s geographical expanse. Human activities (HA) contributed 3.93% to these changes, while climatic factors (CC) contributed 17.79%. Additionally, our projections indicate that EEQ is poised to continue improving in 56.70% of China’s territory in the foreseeable future. However, the Loess Plateau, Tarim Basin, and Inner Mongolia Plateau are anticipated to experience a declining trend. Consequently, within the context of global climate change, the judicious management of human activities emerges as a critical imperative for maintaining EEQ in China. This study, bridging existing gaps in the literature, furnishes a scientific foundation for comprehending the evolving dynamics of EEQ in China and informs the optimization of management policies in this domain.

Lateral organ boundary Domain (LBD) proteins are plant-specific transcription factors that play a key role in plant lateral organ development and stress tolerance. However, LBD gene has not been identified in the common bean (Phaseolus vulgaris L.). Here, a total of 47 common bean LBD genes (PvLBDs) were identified. Members of the same subfamily had similar genetic structures. Synteny analysis indicated that LBDs in the common bean genome have greater collinearity with soybean (Glycine max L.) than with Arabidopsis and rice (Oryza sativa L.). Additionally, 9 pair of segmental duplication genes were identified by collinearity analysis. Phytozome data analysis showed significant differences in PvLBD gene expression abundance between different developmental stages of the same tissue. The qRT-PCR results showed that NaCl, CdCl2, and HgCl2 stresses up-regulated 19% and down-regulated 81% of the PvLBD genes. This study provides a basis for further analysis of the function of the PvLBD gene family.

Sugar Will Eventually be Exported Transporters (SWEET) proteins function as sugar transporters that play key roles in plant growth, development, and biotic and abiotic stress responses. However, little is known about the SWEET gene family in common bean (Phaseolus vulgaris L.). In this study, 24 putative PvSWEET genes were identified. They can be categorized into four subgroups based on a phylogenetic analysis, exon–intron structure, cis-regulatory elements, and MEME motifs. A collinearity analysis showed that three pairs of segmental duplicated events were identified. The Phytozome database showed that 16 PvSWEET genes were highly expressed in reproductive organs. PvSWEET5 was expressed the most highly in all the tissues tested, while PvSWEET8/9/10/13 were undetectable in the datasets. The results of qRT-PCR analysis showed that PvSWEET24 was significantly up-regulated following treatment with NaCl, CdCl2, and HgCl2, whereas the PvSWEET5 and PvSWEET20 genes displayed a specific negative response to CdCl2 stress. Collectively, this study provides comprehensive information for the role of SWEET gene family in common bean and lays a solid foundation to elucidate the biological function of the PvSWEET gene family, as well as provide insights into the correlation between the PvSWEET genes and responses to metal stresses.

AbstractSulfate transporters (SULTRs) are responsible for the absorption and transport of sulfate in higher plants. They also play a key role in plant growth, development and abiotic stress responses. However, the SULTR gene family in common bean (Phaseolus vulgaris L.) is still not well studied. In this study, 15 PvSULTRs were identified. Phylogenetic analysis divided the PvSULTR genes into four subgroups. Cis-regulatory element analysis of the promoter sequence of the PvSULTR genes showed that many cis-regulatory elements were related to hormone and environmental stresses. Collinearity analysis showed that two PvSULTR gene pairs are duplicated in common bean. Tissue-specific expression analysis of the 15 PvSULTR genes showed different expression patterns in various tissues. Furthermore, real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) analysis showed that PvSULTR1/2/7 genes displayed specific responses to CdCl2 and HgCl2 stresses, whereas PvSULTR11/12 were explicitly induced by NaCl and HgCl2 stresses. These results suggest that PvSULTR family members might function under different mechanisms in response to specific metal stress. This study provides the basis for elucidating the functional diversity of PvSULTR gene family and reveals its role in metal stress response in common bean.

Abstract Background Recent years, idiopathic pulmonary fibrosis (IPF) is thought to be a disease of alveoli as well as small airways. This study aimed to demonstrate the clinical feature, predictor, and prognosis of small airway dysfunction (SAD) in Chinese patients with IPF. Methods We enrolled 416 patients with IPF who hospitalized in Beijing Chao-Yang Hospital from 2000 to 2014 in this study, and the follow-up ended at December 2016. We collected demographic information, clinical examination results, spirometry results, HRCT results, and blood gas results during the study. Logistic regression analysis was used to identify the predictor for SAD. The COX proportional hazard model was used to analysis the prognosis effect of SAD. Results Among all the participants, 165 (39.66%) patients had SAD. FEV1 (% predicted) and FEV3/FVC were significantly associated with SAD in patients with IPF. IPF patients with lower FEV1 (% predicted, OR 30.04, 95% CI 9.61–93.90) and FEV3/FVC (OR 77.76, 95% CI 15.44–391.63) had increased risk for SAD. Patients with SAD were associated with significantly increased risk of mortality in patients with IPF (HR 1.73, 95% CI 1.02–2.92), as well as in IPF patients without other pulmonary comorbidities (COPD, emphysema, and asthma). Conclusions Spirometry-defined SAD was like 40% in patients with IPF. Lower FEV1 (% predicted) and FEV3/FVC were main predictors for SAD. IPF patients with SAD showed poorer prognosis.

Right atrial (RA) structural and functional evaluations have recently emerged as powerful biomarkers for adverse events in various cardiovascular conditions. Quantitative analysis of the right atrium, usually performed with volume changes or speckle-tracking echocardiography (STE), has markedly changed our understanding of RA function and remodeling. Knowledge of reference echocardiographic values and measurement methods of RA volumes and myocardial function is a prerequisite to introduce RA quantitation in the clinical routine. This review describes the methodology, benefits and pitfalls of measuring RA size and function by echocardiography based on the current understanding of right atrial anatomy and physiological function and provides the current knowledge of right atrial function in related cardiac diseases.

Abstract Background Common bean (Phaseolus vulgaris) is an essential crop with high economic value. The growth of this plant is sensitive to environmental stress. Heat shock factor (Hsf) is a family of antiretroviral transcription factors that regulate plant defense system against biotic and abiotic stress. To date, few studies have identified and bio-analyzed Hsfs in common bean. Results In this study, 30 Hsf transcription factors (PvHsf1–30) were identified from the PFAM database. The PvHsf1–30 belonged to 14 subfamilies with similar motifs, gene structure and cis-acting elements. The Hsf members in Arabidopsis, rice (Oryza sativa), maize (Zea mays) and common bean were classified into 14 subfamilies. Collinearity analysis showed that PvHsfs played a role in the regulation of responses to abiotic stress. The expression of PvHsfs varied across different tissues. Moreover, quantitative real-time PCR (qRT-PCR) revealed that most PvHsfs were differentially expressed under cold, heat, salt and heavy metal stress, indicating that PvHsfs might play different functions depending on the type of abiotic stress. Conclusions In this study, we identified 30 Hsf transcription factors and determined their location, motifs, gene structure, cis-elements, collinearity and expression patterns. It was found that PvHsfs regulates responses to abiotic stress in common bean. Thus, this study provides a basis for further analysis of the function of PvHsfs in the regulation of abiotic stress in common bean.

Personalized education has been a widely shared goal pursued by Chinese and foreign educators. As the primary method of teacher–student interaction, the importance of personalized questioning is self-evident. Due to a lack of technical support, teachers rely on their teaching experience to ask questions without considering the learning situation of learners. This results in teaching questioning being unable to support learners’ learning. These questions are relatively shallow and cannot promote the construction and transfer of learners’ knowledge. Cognitive diagnostic technology could diagnose learners’ cognitive states and provide services for personalized teaching. Therefore, a personalized teaching questioning strategy based on learners’ cognitive structure diagnosis was proposed in this study. Firstly, we diagnosed learners’ cognitive structure through usability, distinguishability, and stability. Secondly, we discussed the types of questions that teachers should raise when facing learners in different situations. We also discussed the application of personalized teaching questioning strategies. The experiment took place at M Primary School in Ningxia, China, with the participation of one teacher and ninety-seven fourth-grade students. Seven lessons were observed and videotaped across a range of topics. The study revealed that personalized teaching questioning strategies could improve learners’ academic performance and subject literacy. They can also increase the number of teacher questioning, change the depth of teacher questioning content, and expand the scope of questioning subjects.

Objective: primary Sjögren’s syndrome (pSS) is an autoimmune disease, of which the most common complication is interstitial lung disease (ILD). This study aimed to analyze the clinical value of Krebs von den Lungen-6 (KL-6), carcinoembryonic antigen (CEA), and carbohydrate antigen 153(CA153) in patients with pSS complicated with ILD (pSS-ILD), given that only few studies have evaluated this. Methods: This is a cross-sectional study. Serum KL-6 levels (U/mL) were measured using chemiluminescence immunoassay, and concentrations of serum tumor markers were determined using the immunofluorescence method in 64 cases of pSS-ILD (pSS-ILD group), 23 cases without ILD (non-ILD group), and 45 healthy controls. The correlation between KL-6 and tumor markers as well as lung function was analyzed, and the factors that were associated with pSS-ILD were screened. Results: The serum KL-6 was more abnormally increased in patients with pSS-ILD, and the serum KL-6, CEA, carbohydrate antigen 125 (CA125), and CA153 levels were significantly higher in the pSS-ILD group than in the non-ILD and healthy control groups (p < 0.05). KL-6, CEA, and CA153 were negatively correlated with forced vital capacity (FVC%), forced expiratory volume in 1 s (FEV1%), total lung capacity (TLC%), and diffusing capacity for carbon monoxide (DLCO%) (all p < 0.05). Multivariate logistic analysis showed that KL-6 was an independent factor associated with pSS-ILD. Conclusions: In conclusion, we evaluated the association between clinical values of KL-6, tumor markers, and pSS-ILD, and found that KL-6 and tumor markers such as CEA, CA153, and CA125 in patients with pSS-ILD were higher than in patients with non-ILD, and KL-6 was more abnormally increased and significantly associated with ILD development in patients with pSS.

BackgroundST-segment elevation myocardial infarction (STEMI) in young male patients accounts for a significant proportion of total heart attack events. Therefore, clinical awareness and screening for acute myocardial infarction (AMI) in asymptomatic patients at a young age is required. The gut microbiome is potentially involved in the pathogenesis of STEMI. The aim of the current study is to develop an early risk prediction model based on the gut microbiome and clinical parameters for this population.MethodsA total of 81 young males (age

ObjectivesWe sought to evaluate the prognostic value of blood routine parameters and biochemical parameters, especially inflammation-related biomarkers, and establish an inflammation-related prognostic model in Chinese patients with idiopathic pulmonary fibrosis (IPF).Material/methodsPatients diagnosed as IPF at Beijing Chaoyang Hospital and aged 40 years and older were consecutively enrolled from June 2000 to March 2015, and finally, a total of 377 patients were enrolled in the derivation cohort. The follow-up ended in December 2016. We used Cox proportional hazard model to calculate the hazard ratio (HR) and establish the prognostic model. The discrimination and calibration of the prognostic model were evaluated in an independent validation cohort enrolled from China-Japan Friendship Hospital between January 2015 and December 2019.ResultsMultivariate analysis revealed that patients with elevated monocyte-to-red blood cell count ratio (MRR) and monocyte counts showed increased risk of mortality. The clinical-physiological-biomarker (CPB) index and CPB stage we established in this study were a significant predictor, and the C-index for CPB index and CPB stage in the validation cohort was 0.635 (95% CI: 0.558–0.712) and 0.619 (95% CI: 0.544–0.694), respectively. Patients in CPB stage III had the poorest survival.ConclusionWe developed and validated a new inflammation-related prognostic model (CPB index and CPB stage) which was integration of age, gender, FVC (%, predicted), DLCO (%, predicted), Charlson Comorbidity Index, and blood monocyte counts. This prediction model exhibited strong ability in predicting mortality in Chinese patients with IPF.

The hedonic tone of an environmental odor is a powerful predictor of annoyance. Pertinent field surveys combined with laboratory analysis of landfill, pharmaceutical factories and rubber factories have been conducted, with the purpose of obtaining a behavior curve of the hedonic tone for specific odor emissions, and comparing the annoyance potential and odor persistence of the sources under investigation. The 9-point scale was used to determine the hedonic tone, and the odor concentration was measured using the Triangle Odor Bag Method. The concentration to be presented to panel members comprises a range of 5 or 6 dilution steps which differ by a factor of approximately 3. Using a suitable curve fitting procedure, a line can be fitted through the points obtained in the experiment. Characteristic H values at any concentration can be derived from the hedonic behavior curve. The relationship between the hedonic tone and lgOC conforms to the quadratic polynomial for the three sources. The persistence of odor is expressed as a dose (concentration) response and (intensity) function. According to the rate of change in odor intensity, the pharmaceutical odor is the strongest, followed by the landfill odor, and then the rubber odor. Annoyance potential is calculated by multiplying lgOC with the max hedonic value, meaning that the three sources are sorted as follows: rubber factory>landfill>pharmaceutical factory. This study will further the understanding of the sensory characteristics of different odor source

Objective: To explore the clinical role of contrast-enhanced ultrasound (CEUS) in a preoperative evaluation of early endometrial carcinoma. Methods: This study included 14 patients who underwent preoperative CEUS and contrast-enhanced magnetic resonance imaging (CEMRI) and were ultimately diagnosed with stage I endometrial carcinoma from December 2019 to December 2020. The parameters of the time-intensity curve (TIC) were compared with the endometrial carcinoma group, the invaded myometrium group, and the normal myometrium group. Results: TIC parameters between the endometrial carcinoma group and the invaded myometrium group were similar. Compared with the normal myometrium group, the time to peak (TTP) was significantly shorter and the ascending slope (AS) was significantly higher in the endometrial carcinoma group. The TTP of the invaded myometrium group was shorter than that of the normal myometrium group and the peak intensity (PI) was higher than that of the normal myometrium group. We then compared the TIC parameters between the endometrial carcinoma group and the invaded myometrium group after adjusting for the normal myometrium group, and the results still did not show any difference. Of the 14 cases of endometrial carcinoma, 9 cases were diagnosed by CEMRI and were consistent with the pathology results, 1 case was underestimated, and 4 cases were overestimated; while 11 cases diagnosed were diagnosed by CEUS and were consistent with the pathology results, 1 case was underestimated, and 2 cases were overestimated. Conclusions: The contrast pulse sequencing technique used in the CEUS examinations performed well in evaluating the extent of the endometrial carcinoma. Future studies with larger sample sizes are needed to determine the applicability and value of this new procedure during preoperative assessments of early endometrial carcinoma.

The gut microbiome is an essential component of the intestinal mucosal barrier, critical in regulating intestinal permeability. Microbiome dysbiosis and intestinal permeability changes are commonly encountered conditions in patients with cirrhosis and are closely related to its development and further complications. However, alterations in the gut microbiome and intestinal permeability in chronic hepatitis B virus (HBV) patients with cirrhotic portal hypertension after undergoing a splenectomy plus pericardial devascularization (SPD) have not been investigated. This study recruited 22 patients who were measured against themselves on the study parameters before and after an SPD, along with 20 healthy controls. Methodologically, fecal samples were collected for gut microbiome analysis by 16S ribosomal DNA sequencing, and peripheral blood samples were obtained to examine the liver function and intestinal permeability. This study showed that the community structure of the gut microbiomes in patients before the SPD exhibited obvious differences from those in the healthy control group. They also exhibited a decreased bacterial community richness, increased intestinal permeability, and enhanced inflammation compared with the healthy controls. These issues were further aggravated two weeks after the SPD. There was also evidence of significantly higher abundances of Streptococcaceae, Enterobacteriaceae, and Enterococcaceae than those in the healthy control group. However, 12 months after the surgery, 12 of the 16 patient-associated genera recovered, of which 10 reached normal levels. Additionally, the microbiome diversity increased; the bacterial composition was back to a level similar to the healthy controls. Liver function, intestinal permeability, and inflammation levels all improved compared with preoperative levels. Furthermore, correlation analyses indicated that the five recovered bacterial taxa and the Shannon diversity index were correlated with several improved clinical indicators. Altogether, the improvements in the liver function and intestinal permeability in HBV-related cirrhotic patients may be related to the restoration of the gut microbiome after an SPD.

Innate immune cells respond to a number of environmental cues including TLR signalling. Here the authors implicate mechanical sensor Piezo1 in the TLR4 mediated host response to bacterial infection and implicate it in the enhancement of macrophage mediated host response.

Abstract Objective The aim of this study is to examine the relationship between rectal–vaginal pressure and symptomatic rectocele in patients with pelvic organ prolapse (POP). Method Patients with posterior vaginal prolapse staged III or IV in accordance with the POP Quantitation classification method who were scheduled for pelvic floor reconstructive surgery in the years 2016–2019 were included in the study. Rectocele was diagnosed using translabial ultrasound, and obstructed defecation (OD) was diagnosed in accordance with the Roma IV diagnostic criteria. Both rectal and vaginal pressure were measured using peritron manometers at maximum Vasalva. To ensure stability, the test was performed three times with each patient. Results A total of 217 patients were enrolled in this study. True rectocele was diagnosed in 68 patients at a main rectal ampulla depth of 19 mm. Furthermore, 36 patients were diagnosed with OD. Symptomatic rectocele was significantly associated with older age (p 27.5 cm H2O was suggested as the cut-off point of the elevated pressure gradient.

Objective: Cardiomyocyte hypertrophy is an important feature of hypertension. However, its molecular underpinnings, especially the signaling cascades, remain unclear. Here we hypothesized that a protein kinase D (PKD)-dependent extracellular signal-regulated kinase 5 (ERK5) pathway was able to regulate downstream myocyte enhancer factor 2D (MEF2D), affecting prohypertrophic responses to angiotensin II (Ang II). Methods: Neonatal rat cardiomyocytes from 2- to 3-day-old Sprague-Dawley rats were prepared and Western blot, real-time quantitative PCR and immunofluorescence staining were used to assess the activation and translocation of pathway signaling molecules. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression and [3H]-leucine (Leu) incorporation were measured to determine cell hypertrophy. Results: Elevated levels of phosphorylated PKD (p-PKD) and ERK5 (p-ERK5) were observed in cardiomyocytes stimulated with Ang II, while silencing protein kinase C epsilon (PKCɛ) resulted in significantly lower levels of p-PKD. Furthermore, Ang II-induced ERK5 activated translocation was mediated by the PKD pathway. Consequently, inhibiting PKCɛ, PKD and ERK5 by siRNA significantly attenuated Ang II-induced MEF2D activation, ANP and BNP mRNA expression, and [3H]-Leu incorporation. Conclusions: Our studies are the first to show that the PKCɛ/PKD/ERK5/MEF2D pathway plays an important role in the cardiomyocyte hypertrophy response to Ang II. Resumo: Objetivos: A hipertrofia dos cardiomiócitos é uma característica importante da hipertensão arterial. No entanto, os mecanismos moleculares da hipertrofia, especialmente as cascatas sinalizadoras, são ainda pouco claros. Neste contexto colocamos a hipótese de que a proteína quinase D (PQD) – dependente da via da quinase 5 (ERK5) determinada pelo sinal extracelular –possa regular a jusante o fator intensificador do miócito -2D (FIM2D), afetando as respostas pro-hipertróficas à Ang II. Métodos: Foram preparados os cardiomiócitos de ratos neonatais de dois a três anos, Sprague-Dawley, tendo sido utilizados os testes de Western blot, a PCR quantitaiva Real-Time (PCRq-RTRT) e a coloração por imunofluorescência para avaliar a ativação e a translocação das moléculas das vias de sinalização. O fator natriurético auricular (FNA), o peptídeo natriurético auricular tipo B (BNP) e a incorporação [3H]-Leu foram igualmente medidos para determinar a hipertrofia celular. Resultados: Nos cardiomiócitos estimulados com Ang II foram observados níveis elevados de PCD fosforilada (PCD-f) e ERK5 (ERK5-p), tendo a proteínaquinase C epsilon silenciada apresentado níveis significativamente inferiores de PQD-f. Além disso, a translocação ativada de ERK5 induzida pela Ang II foi mediada pela via PCD. Consequentemente, a inibição de PCDɛ, de PCD e de ERK5 através de siRNA atenuou significativamente a ativação de FIM2D induzida pela Ang II, o FNA e a expressão de mRNA BNP, bem como a incorporação de Leucina-[3H]. Conclusões: O nosso estudo demonstra pela primeira vez que as vias PCCɛ/PCD/ERK5/FIM 2D desempenham um papel importante na resposta hipertrófica dos cardiomiócitos a Ang II.

The rapid development of data analytic technologies has advanced personalized learning and increased its popularity in K-12 education significantly. Specifically, one fundamental step in personalized learning is knowledge proficiency diagnosis which reveals blind spots in students’ knowledge. However, existing approaches to diagnosis either exploit data from a one-time assessment for the cognitive diagnosis (ignoring the previous historical interactions) or trace the knowledge state using recurrent neural networks to predict students’ future performance (ignoring the cognitive features). To this end, this study proposes a dynamic approach to knowledge diagnosis integrating cognitive features with a key-value memory network to store latent exercise information and capture long-term temporal features based on cognitive psychology. Specifically, given the characteristics of assessment data in China, our approach mainly aims to model sequence data with cognitive features, including forgetting and learning. Two corresponding gates are used to weaken the knowledge memory and strengthen the repeated knowledge memory over time, respectively, in the memory updating process. Finally, to evaluate our approach, we conducted extensive experiments on four real-world datasets collected from K-12 education. The results show that the approach can effectively process the time sequence in education, whose prediction results are better and more stable than other existing baseline models. We also conducted experiments for parameter sensitivity, different feature integration methods, and the effectiveness of cognitive features to ensure that the models achieved the best results. The application visualization further confirms the practicability of our approach in dealing with problems of dynamic knowledge diagnosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disorder with a poor prognosis. Although dihydromyricetin (DHM), extracted from vine tea and other Ampelopsis species, has been proven to have anti-inflammatory and antioxidant functions, the effects of DHM on IPF remain unclear.Methods: The effects of DHM on the differentiation, migration, proliferation, and respiratory functions of primary mouse lung fibroblasts (PMLFs) and primary human lung fibroblasts (PHLFs) were detected by western blotting, the Transwell assay, EdU staining, and the Mito Stress test. Then, the impacts of DHM on bleomycin (BLM)-induced pulmonary fibrosis were evaluated by pathological staining, western blotting, and coimmunofluorescence staining. The signaling pathway influenced by DHM was also investigated.Results: DHM could regulate the differentiation of fibroblasts to myofibroblasts and suppress the abnormal migration, proliferation, and respiratory functions of myofibroblasts induced by TGF-β1 or myofibroblasts from IPF patients. DHM could also alleviate pulmonary fibrosis induced by BLM. All these effects were achieved by regulating the STAT3/p-STAT3/GLUT1 signaling pathway.Conclusion: DHM could regulate the abnormal functions of myofibroblasts induced by TGF-β1 and myofibroblasts from IPF patients and alleviate pulmonary fibrosis induced by BLM; thus, DHM might be a candidate medicinal treatment for IPF.

ObjectiveInterstitial lung diseases (ILDs) secondary to anti-synthetase syndrome (ASS) greatly influence the prognoses of patients with ASS. Here we aimed to investigate the peripheral immune responses to understand the pathogenesis of this condition.MethodsWe performed single-cell RNA sequencing (scRNA-seq) of peripheral blood mononuclear cells (PBMCs) from 5 patients with ASS-ILD and 3 healthy donors (HDs). Flow cytometry of PBMCs was performed to replenish the results of scRNA-seq.ResultsWe used scRNA-seq to depict a high-resolution visualization of cellular landscape in PBMCs from patients with ASS-ILD. Patients showed upregulated interferon responses among NK cells, monocytes, T cells, and B cells. And the ratio of effector memory CD8 T cells to naïve CD8 T cells was significantly higher in patients than that in HDs. Additionally, Th1, Th2, and Th17 cell differentiation signaling pathways were enriched in T cells. Flow cytometry analyses showed increased proportions of Th17 cells and Th2 cells, and decreased proportion of Th1 cells in patients with ASS-ILD when compared with HDs, evaluated by the expression patterns of chemokine receptors.ConclusionsThe scRNA-seq data analyses reveal that ASS-ILD is characterized by upregulated interferon responses, altered CD8 T cell homeostasis, and involvement of differentiation signaling pathways of CD4 T cells. The flow cytometry analyses show that the proportions of Th17 cells and Th2 cells are increased and the proportion of Th1 cells is decreased in patients with ASS-ILD. These findings may provide foundations of novel therapeutic targets for patients with this condition.

Fatty acid metabolism, including the de novo synthesis, uptake, oxidation, and derivation of fatty acids, plays several important roles at cellular and organ levels. Recent studies have identified characteristic changes in fatty acid metabolism in idiopathic pulmonary fibrosis (IPF) lungs, which implicates its dysregulation in the pathogenesis of this disorder. Here, we review the evidence for how fatty acid metabolism contributes to the development of pulmonary fibrosis, focusing on the profibrotic processes associated with specific types of lung cells, including epithelial cells, macrophages, and fibroblasts. We also summarize the potential therapeutics that target this metabolic pathway in treating IPF.

Radiometric normalization, as an essential step for multi-source and multi-temporal data processing, has received critical attention. Relative Radiometric Normalization (RRN) method has been primarily used for eliminating the radiometric inconsistency. The radiometric transforming relation between the subject image and the reference image is an essential aspect of RRN. Aimed at accurate radiometric transforming relation modeling, the learning-based non-linear regression method, Support Vector machine Regression (SVR) is used for fitting the complicated radiometric transforming relation for the coarse-resolution data-referenced RRN. To evaluate the effectiveness of the proposed method, a series of experiments are performed, including two synthetic data experiments and one real data experiment. And the proposed method is compared with other methods that use linear regression, Artificial Neural Network (ANN) or Random Forest (RF) for radiometric transforming relation modeling. The results show that the proposed method performs well on fitting the radiometric transforming relation and could enhance the RRN performance.

Objective: Current studies focus on the prevalence rate of lung cancer in idiopathic pulmonary fibrosis and connective tissue disease-associated interstitial lung disease (CTD-LID). Our aim was to investigate the prevalence of malignancies in patients with various subtypes of ILD. Methods: A total of 5350 patients diagnosed with ILD between January 2015 and December 2021 were retrospectively included. The prevalence of different malignancies and different ILDs was assessed using complete follow-up data. Results: A total of 248 patients (139 males; 65—IQR, 57 to 72—years) out of 5350 patients with ILD were confirmed with malignancies. A total of 69% of patients with ILD and malignances were older than 60 years old. The prevalence of malignancies in ILD patients was 4.6%, and lung cancer had the most common incidence of 1.9%, followed by malignancies in the digestive system of 0.9%. Among the different ILD subtypes, the prevalence of malignancies such as organizing pneumonia (OP), idiopathic pulmonary fibrosis (IPF), anti-neutrophil cytoplasmic antibodies-associated vasculitis-related ILD(AAV-ILD), nonspecific interstitial pneumonia (NSIP), CTD-ILD, hypersensitivity pneumonitis (HP), sarcoidosis, and other types of ILD was 6.8%, 5.0%, 4.7%, 4.3%, 2.5%, 2.2%, 1.2%, and 6.9%, respectively. The incidence of lung cancer as the most common tumor in IPF was 3.9%, with adenocarcinoma predominating (1.7%). The highest rate of malignancy occurring in RA of CTD-ILD was 2.4%. Conclusion: Older patients with ILD (≥60 years) including OP, IPF, AAV-ILD, NSIP, CTD-ILD, and HP, were associated with a higher incidence of malignancy, especially males aged from 60 to 69 years. These epidemiological results indicate that it is essential for physicians to pay more attention to the screening of and management strategies for different malignancies, according to the specific ILD subtypes.

Rapid and accurate mapping of soil organic carbon (SOC) is of great significance to understanding the spatial patterns of soil fertility and conducting soil carbon cycle research. Previous studies have dedicated considerable efforts to the spatial prediction of SOC content, but few have systematically quantified the effects of environmental covariates selection, the spatial scales and the model types on SOC prediction accuracy. Here, we spatially predicted SOC content through digital soil mapping (DSM) based on 186 topsoil (0–20 cm) samples in a typical hilly red soil region of southern China. Specifically, we first determined an optimal covariate set from different combinations of multiple environmental variables, including multi-sensor remote sensing images (Sentinel-1 and Sentinel-2), climate variables and DEM derivatives. Furthermore, we evaluated the impacts of spatial resolution (10 m, 30 m, 90 m, 250 m and 1000 m) of covariates and the model types (three linear and three non-linear machine learning techniques) on the SOC prediction. The results of the performance analysis showed that a combination of Sentinel-1/2-derived variables, climate and topographic predictors generated the best predictive performance. Among all variables, remote sensing covariates, especially Sentinel-2-derived predictors, were identified as the most important explanatory variables controlling the variability of SOC content. Moreover, the prediction accuracy declined significantly with the increased spatial scales and achieved the highest using the XGBoost model at 10 m resolution. Notably, non-linear machine learners yielded superior predictive capability in contrast with linear models in predicting SOC. Overall, our findings revealed that the optimal combination of predictor variables, spatial resolution and modeling techniques could considerably improve the prediction accuracy of the SOC content. Particularly, freely accessible Sentinel series satellites showed great potential in high-resolution digital mapping of soil properties.

As a major branch of Non-Photorealistic Rendering (NPR), image stylization mainly uses computer algorithms to render a photo into an artistic painting. Recent work has shown that the ex-traction of style information such as stroke texture and color of the target style image is the key to image stylization. Given its stroke texture and color characteristics, a new stroke rendering method is proposed. By fully considering the tonal characteristics and the representative color of the original oil painting, it can fit the tone of the original oil painting image into a stylized image whilst keeping the artist’s creative effect. The experiments have validated the efficacy of the proposed model in comparison to three state-of-the-arts. This method would be more suitable for the works of pointillism painters with a relatively uniform style, especially for natural scenes, otherwise, the results can be less satisfactory.

Background: Lysyl oxidases (LOXs), including LOX, LOXL1, LOXL2, LOXL3, and LOXL4, catalyze the formation of a cross-link between elastin (ELN) and collagen. Multiple LOX mutations have been shown to be associated with the occurrence of aortic dissection (AD) in humans, and LOX-knockout mice died during the perinatal period due to aortic aneurysm and rupture. However, the expression levels and roles of other LOX members in AD remain unknown.Methods: A total of 33 aorta samples of AD and 15 normal aorta were collected for LOXs mRNA and protein levels detection. We also analyzed the datasets of AD in GEO database through bioinformatics methods. LOXL2 and LOXL3 were knocked down in primary cultured human aortic smooth muscle cells (HASMCs) via lentivirus.Results: Here, we show that the protein levels of LOXL2 and LOXL3 are upregulated, while LOXL4 is downregulated in AD subjects compared with non-AD subjects, but comparable protein levels of LOX and LOXL1 are detected. Knockdown of LOXL2 suppressed MMP2 expression, the phosphorylation of AKT (p-AKT) and S6 (p-S6), but increased the mono-, di-, tri-methylation of H3K4 (H3K4me1/2/3), H3K9me3, and p-P38 levels in HASMCs. These results indicate that LOXL2 is involved in regulation of the extracellular matrix (ECM) in HASMCs. In contrast, LOXL3 knockdown inhibited PCNA and cyclin D1, suppressing HASMC proliferation. Our results suggest that in addition to LOX, LOXL2 and LOXL3 are involved in the pathological process of AD by regulating ECM and the proliferation of HASMCs, respectively. Furthermore, we found that LOXL2 and LOXL4 was inhibited by metformin and losartan in HASMCs, which indicated that LOXL2 and LOXL4 are the potential targets that involved in the therapeutic effects of metformin and losartan on aortic or aneurysm expansion.Conclusions: Thus, differential regulation of LOXs might be a novel strategy to prevent or treat AD.

Abstract As a widely used renewable energy, migrating to wind power can help reduce air pollution and CO2 emissions. However, the construction of wind farms could have certain impacts on the local ecology and meteorology. Based on satellite observations along with the ERA‐Interim reanalysis meteorology, this study examines the difference of vegetation characteristics, local wind speed, and surface temperature between the wind power regions and adjacent comparison areas in XilinGol. It shows that the construction of wind farms results in significant differences (p = 0.01) of normalized difference vegetation index values in the study areas compared to the adjacent areas in summer. The construction of the wind farms in study area has considerable influence on the change of local vegetation growth and related meteorological variables. It reduces the fraction of grassland, disrupts the wind field when speed are less than 4 m/s, and changes the spatial pattern of temperature during daytime and nighttime. However, the influence decreases with time after the installment of wind turbines. This study suggests that it is necessary to assess the impact of renewable energy construction on ecological environment and local climate, particularly for the short‐term period after its installment.

The present study was designed to determine the role of PKD in vascular remodeling (VR) in Spontaneously hypertensive rats (SHRs). Increased SBP, VR and PKD activation were prominent in SHRs. The SBP has a positive correlation with the activation of PKD in SHRs. The ratio of media to lumen (MT/LD), volume fraction of collagen (VFC), hydroxyproline, IL-6, TNF-α and nitrotyrosine content were significantly related to the activated PKD. It may be concluded that PKD plays a central role in VR, and the mechanism may be related to its regulation of hypertrophy, fibrosis, inflammation and oxidative stress.

Abstract Background Pancreatic cancer stem cells (CSCs), a special population of cells, renew themselves infinitely and resist to various treatment. Gramicidin A (GrA), an ionophore antibiotic derived from microorganism, can form channels across the cell membrane and disrupt cellular ionic homeostasis, leading to cell dysfunction and death. As reported, the ionophore antibiotic salinomycin (Sal) has been proved to kill CSCs effectively. Whether GrA owns the potential as a therapeutic drug for CSCs still remains unknown. This study investigated the effect of GrA on pancreatic CSCs and the mechanism. Methods Tumorsphere formation assay was performed to assess pancreatic CSCs self-renewal potential. In vitro hemolysis assay was determined to test the borderline concentration of GrA. CCK-8 assay was used to detect pancreatic cancer cell proliferation capability. Flow cytometry was performed to detect cell apoptosis and mitochondrial membrane potential. Scanning and transmission electron microscopy was used to observe ultrastructural morphological changes on cell membrane surface and mitochondria, respectively. Western blot analysis was used to determine relative protein expression levels. Immunofluorescence staining was performed to observe CD47 re-distribution. Results GrA at 0.05 μM caused tumorspheres disintegration and decrease in number of pancreatic cancer BxPC-3 and MIA PaCa-2 cells. GrA and Sal both inhibited cancer cell proliferation. The IC50 values of GrA and Sal for BxPC-3 cells were 0.025 μM and 0.363 μM; while for MIA PaCa-2 cells were 0.032 μM and 0.163 μM, respectively. Compared on equal concentrations, the efficacy of GrA was stronger than that of Sal. GrA at 0.1 μM or lower did not cause hemolysis. GrA induced ultrastructural changes, such as the decrease of microvilli-like protrusions on cell surface membrane and the swelling of mitochondria. GrA down-regulated the expression levels of CD133, CD44, and CD47; in addition, CD47 re-distribution was observed on cell surface. Moreover, GrA showed synergism with gemcitabine in suppressing cancer cell proliferation. Conclusions The study found that GrA was highly active against pancreatic CSCs. It indicates that GrA exerts inhibitory effects against pancreatic CSCs associated with CD47 down-regulation, implying that GrA might play a positive role in modulating the interaction between macrophages and tumor cells.

Immune cells produce reactive oxygen species (ROS) to eliminate pathogens, but cell-spontaneous death and ageing may also be induced. Here the authors show that, upon sensing ROS, Mst1/2 kinases modulate the activity of Nrf2 transcription factor and downstream genetic programs to protect mouse macrophages from death and ageing.

Background: Higenamine (HG) is an active compound derived from Aconiti root with a cardiotonic effect. It has been approved by the Chinese SFDA for clinical trials due to its effect as a potent inotropic and chronotropic agent in the heart. However, the direct mode of action of HG on cardiac electrophysiology is unclear. Methods: The experiments were performed at both cell levels and the isolated organ. The major cardiac ion currents and the action potential duration (APD) were measured using patch-clamps in single guinea-pig left ventricular myocytes. ECG was recorded in isolated guinea pig hearts. Results: In the left ventricular myocytes, HG increased ICa-L and IKs in concentration- and voltage-dependent manners in the left ventricular myocytes. It potentiated the ICa-L and IKs simultaneously for synchronization. The EC50 values were 0.27 μM and 0.64 μM for the ICa-L and IKs, respectively. HG (0.1 μM, 0.5 μM and 1 μM) had no effect on the IKr and INa. HG slightly prolonged APD at lower concentrations, and shortened the APD at higher concentrations. HG can induce the delayed after depolarization (DAD), which showed some pro-arrhythmic effect. In the isolated perfused heart, HG increased the heart rate via an action on the sinoatrial node cells, but did not induce cardiac arrhythmias, even at high concentrations. The EC50 value for the sinoatrial node that controls the heart rate was 0.13 μM. The sinoatrial node cells appeared to be more sensitive than ventricular myocytes to HG. The effects of HG on ventricular cells and sinoatrial node cells were both mediated through stimulation of β1-AR. Conclusion: We show for the first time that HG produced a predominant action on the sinoatrial node. HG appears to control the cardiac electrophysiology through its predominant effect on the sinoarial node cells, without induction of the ectopic activity that causes cardiac arrhythmias. Thus, HG might be useful for the treatment of bradycardia.

Aging is the crucial co-morbidity that prevents the full cardioprotection against myocardial ischemia/reperfusion (I/R) injury. Combination therapy as a promising strategy may overcome this clinical problem. This study aimed to investigate the cardioprotective effects of Ginsenoside compound-Mc1 (GMc1) and Dendrobium Nobile Lindl (DNL) in myocardial I/R injury and explore the involvement of the TLR4/NF-κB signaling pathway in aged rats. In vivo I/R injury and myocardial infarction was established by temporary coronary ligation in 22–24 months’ old Sprague Dawley male rats. GMc1 (10 mg/kg) and DNL (80 mg/kg) were administered intraperitoneally for 4 weeks and orally for 14 days, respectively, before I/R injury. Infarct size was measured through triphenyl-tetrazolium-chloride staining. ELISA assay was conducted to quantify the levels of cardiotroponin, and myocardial content of TNF-α and glutathione. Western blotting was employed to detect the expression of TLR4/MyD88/NF-κB proteins. GMc1 and DNL significantly reduced the infarct size to a similar extent ( p

Introduction Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease characterised by a fibrotic histological pattern found in usual interstitial pneumonia. Its causes, pathogenesis, clinical phenotype and molecular mechanisms are poorly defined. Large-scale, multicentre studies are warranted to better understand IPF as a disease in China, its associated risk factors, clinical characteristics, diagnosis, disease progression and treatment.Methods and analysis The Idiopathic Pulmonary Fibrosis Registry China Study (PORTRAY) is a prospective, multicentre registry study of patients with IPF in China. Eight hundred patients will be enrolled over a 36-month period and followed for at least 3 years to generate a comprehensive database on baseline characteristics and various follow-up parameters including patient-reported outcomes. Biological specimens will also be collected from patients to develop a library of blood, bronchoalveolar lavage fluid and lung biopsy samples, to support future research. As of 15 December 2019, 204 patients from 19 large medical centres with relatively high IPF diagnosis and treatment rates had been enrolled. Patient characteristics will be presented using descriptive statistics. The Kaplan-Meier method will be used for survival analyses. Repeated measures will be used to compare longitudinal changes in lung function, imaging and laboratory tests. Results following analysis have been projected to be available by July 2025.Ethics and dissemination The study protocol was reviewed and approved by the Institutional Review Board from all the study sites currently recruiting patients. Study results will be published in peer-reviewed journals.Trial registration number NCT03666234.

The rapid development of urbanization and population growth in China has posed a major threat to the green sustainable development of the ecological environment. However, the impact of urbanization on the eco-environmental quality (EEQ) in China remains to be developed. Understanding their interactive coupling mechanism is of great significance to achieve the urban sustainable development goals. By using multi-source remote sensing data and the coupling coordination degree model (CCDM), we intended to answer the question “What are the temporal and spatial characteristics of urbanization and EEQ in China on the pixel scale during 2000–2013, and what is the coupling mechanism between the urbanization and the EEQ?”. To answer these questions, we explored the coupling mechanism between urbanization and the EEQ in China with a combined mathematical and graphics model. The results show that the urbanization and the coupling coordination degree (CCD) of the whole region continually increased from 2000 to 2013, especially in the three major urban agglomerations, with a spatial distribution pattern that was “high in the east and low in the west”. Most importantly, from 2000 to 2013, the CCD type of cities in China gradually evolved from uncoordinated cities to coordinated cities. Additionally, the decisive factor affecting the CCD from 2000 to 2013 was the development of urbanization, and the degree at which urbanization had an impact on CCD was about 8.4 times larger than that of the EEQ. At the same time, the rapid urbanization that has occurred in some areas has led to a significant decline in the EEQ, thus indicating that China needs to increase its protection of the ecological environment while pursuing social and economic development in the future. This study makes up for the deficiencies in the existing literature and investigates the long-term coupling of the EEQ and urbanization in China, thereby providing a new research perspective for the sustainable development of China and even the world in the future.

Generating response with both coherence and diversity is a challenging task in generation-based chatbots. It is more difficult to improve the coherence and diversity of dialog generation at the same time in the response generation model. In this article, we propose an improved method that improves the coherence and diversity of dialog generation by changing the model to use gamma sampling and adding attention mechanism to the knowledge-guided conditional variational autoencoder. The experimental results demonstrate that our proposed method can significantly improve the coherence and diversity of knowledge-guided conditional variational autoencoder for response generation in generation-based chatbots at the same time.

Summary: In multi-criteria recommender systems, matrix factorization characterizes users and items via latent factor vectors inferred from user-item rating patterns. However, two-dimensional matrix factorization models may not be able to cope with the recommendation problem that involves additional criterion-specific rating data. This study introduces a tensor factorization method to handle three-dimensional user-item-criterion rating data. Moreover, we observe that using single global tensor factorization alone may not be sufficient to characterize diverse preferences among different groups of users, and a combined global and local tensor factorization method (GLTF) for multi-criteria recommendation is thus proposed. One key benefit of the GLTF is that it can leverage global user-item-criterion rating patterns while also exploiting local user-subset specific rating behaviors to jointly infer the latent factor representations for users, items, and specific item criteria. Experimental results, which used real-life data available to the public, demonstrated that the GLTF is superior to well-established baseline methods. The Bigger Picture: We propose a global and local tensor factorization method (GLTF) to solve the multi-criteria recommendation problem commonly experienced when e-commerce systems recommend products to users based on multiple different ratings. The method uses additional criterion-specific ratings in addition to existing user-item rating data for better recommendations. It can jointly learn a global predictive model and multiple local predictive models, not only by discovering the overall structure of the entire rating tensor but also by capturing diverse rating behaviors of users in individual subtensors. The GLTF can take advantage of the user's multi-criteria rating information to discover the user's behavior, predict the information and products that the user is interested in, and obtain more accurate recommendation results. In the future, we plan to apply the GLTF in a much larger dataset for evaluation and will improve the model to mitigate the bottleneck caused by the data sparsity problem.

Skeleton network extraction is a crucial context in studying the core structure and essential information on complex networks. The objective of this paper is to introduce the novel network extraction method, namely, TPKS-skeleton, for investigating the global terrorism network. Our method aims to reduce the network’s size while preserving key topology and spatial features. A TPKS-skeleton comprises three steps: node evaluation, similarity-based clustering, and skeleton network reconstruction. The importance of skeleton nodes is quantified by the improved topology potential algorithm. Similarity-based clustering is then integrated to allow detecting high incident concentrations and allocating the important nodes according to the event features and spatial distribution. Finally, the skeleton network can be reconstructed by aggregating high-influential nodes from each cluster and their simplified edges. To verify the efficiency of the proposed method, we carry out three classes of a network assessment framework: node-equivalence assessment, network-equivalence assessment, and spatial information assessment. For each class, various assessment indexes were performed using the original network as a benchmark. The results verify that our proposed TPKS-skeleton outperforms other competitive methods in particular node-equivalence by Spearman rank correlation and high network structural-equivalence defined by quadratic assignment procedure. In the spatial perspective, the TPKS-skeleton network preserves reasonably all kinds of spatial information. Our study paves the way to extract the optimal skeleton of the global terrorism network, which might be beneficial for counterterrorism and network analysis in wider areas.