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Abstract Physical exercise is a cornerstone for preventing diet-induced obesity, while it is unclear whether physical exercise could offset high-fat, high-calories diet (HFCD)-induced cardiac dysfunction. Here, mice were fed with HFCD and simultaneously subjected to physical exercise. As expected, physical exercise prevented HFCD-induced whole-body fat deposition. However, physical exercise exacerbated HFCD-induced cardiac damage. Further metabolomic analysis results showed that physical exercise induced circulating lipid redistribution, leading to excessive cardiac lipid uptake and lipotoxicity. Our study provides valuable insights into the cardiac effects of exercise in mice fed with HFCD, suggesting that counteracting the negative effect of HFCD by simultaneous physical exercise might be detrimental. Moreover, inappropriate physical exercise may damage certain organs even though it leads to weight loss and overall metabolic benefits. Of note, the current findings are based on animal experiments, the generalizability of these findings beyond this specific diet and mouse strain remains to be further explored.

Abstract Dried blood spot (DBS) sampling offers significant advantages over conventional blood collection methods, such as reduced sample volume, minimal invasiveness, suitability for home-based sampling, and ease of transport. However, understanding the effects of variable storage temperatures and times on metabolite stability is crucial due to varying intervals and delivery conditions between sample collection and metabolomics analysis. To minimize biological variances, all samples were collected from the same individual simultaneously and stored at three different temperatures (4 °C, 25 °C, and 40 °C) for diverse time points (3, 7, 14, and 21 days). Metabolic profiling was conducted an untargeted gas chromatography-mass spectrometry (GC-MS) and ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS)-based multi-platform metabolomics. Principal component analysis (PCA) showed alterations in metabolite stability at different temperatures, with phosphatidylcholines (PCs) and triglycerides (TAGs) as the first principal component (PC1). Specifically, we identified 69 metabolites that remained stable across all three temperatures over the 21-day period, while 78 metabolites exhibited instability. Furthermore, linear correlations between metabolite intensity and storage time were observed. Overall, our study elucidated the influence of storage temperature and time on specific metabolite stability in DBS samples, providing valuable insights for study design, biomarker selection, and data improvement.

Objective·To explore the effects and possible molecular mechanisms of nanoplastics (NPs) on severe asthma.Methods·A mouse model of severe asthma was established by using house dust mite (HDM) and lipopolysaccharide (LPS) co-stimulation. Polystyrene nanoplastics (PS-NPs) were instilled into the severe asthma mice′s airways. Subsequently, bronchoalveolar lavage fluid (BALF) was collected and lung tissue sections were prepared. Flow cytometry, hematoxylin-eosin (H-E) staining, periodic acid-Schiff (PAS) staining, immunohistochemistry, and terminal dexynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, were used to observe the effects of PS-NPs on airway inflammation, mucus secretion, alveolar structure, and the proliferation and apoptosis of alveolar type Ⅱ epithelial cells (AT2 cells) in severe asthma mice. The CCK-8 assay and Annexin Ⅴ/PI double staining were performed to evaluate the effects of PS-NPs on the proliferation and apoptosis of the mouse AT2 cell line MLE-12. DNA damage in AT2 cells caused by PS-NPs was detected by using anti-γ-H2A.X immunofluorescence staining. The expression of genes in the ATR/Chk1/p53 signaling pathway was detected by real-time fluorescent quantitative polymerase chain reaction (qPCR), Western blotting, Tyramide signal amplification (TSA) multiplex immunofluorescence staining, and immunofluorescence co-localization, respectively. The ATR-specific inhibitor Ceralasertib (AZD6738) was administrated to MLE-12 cells in combination with PS-NPs to evaluate the recovery effect on cell proliferation and apoptosis.Results·Flow cytometry revealed that exposure to PS-NPs increased the total number of inflammatory cells and the number of each type of inflammatory cells in the BALF of mice with severe asthma, with a predominance of neutrophils. H-E and PAS staining showed significant increase in airway inflammatory cell infiltration and mucus secretion, as well as disruption of alveolar structure. In vitro, the CCK-8 assay demonstrated significant, dose-dependent inhibition of MLE-12 cell proliferation by PS-NPs. The Annexin V/PI double staining assay indicated a higher apoptosis rate of (56.20±3.84)% in PS-NP-exposed cells compared to (23.22±2.52)% in the control group. Immunofluorescence staining demonstrated that PS-NPs were phagocytosed by MLE-12 cells and localized around the nucleus. TUNEL staining confirmed enhanced apoptosis in AT2 cells in vivo. The immunofluorescence assay revealed that compared to the control group, the expression of the DNA damage marker γ-H2A.X increased in the experimental group. qPCR, Western blotting, and TSA multiplex staining results showed that PS-NP-induced elevated expression of mRNA and proteins was related to the ATR/Chk1/p53 pathway in MLE-12 cells. Moreover, immunofluorescence co-localization also confirmed the induction of ATR and p53 proteins in AT2 cells in vivo. The ATR-specific inhibitor Ceralasertib partially restored the PS-NP-induced inhibition of cell proliferation and enhancement of apoptosis in MLE-12 cells.Conclusion·NPs exposure leads to DNA damage in AT2 cells, activating the ATR/Chk1/p53 signaling pathway and exacerbating airway inflammation and alveolar damage in mice with severe asthma.

Comprehensive geophysical prospection is an effective technique for karst exploration, but its prediction results usually suffer from significant artificial influence and fuzzy boundaries of karst caves. Based on the machine learning technology, a Gaussian mixture model is used to classify the exploration data of high-density electrical method and data of surface wave method respectively. Then, a Category-boundary algorithm is proposed to further subdivide the classification results, which improves the accuracy of Gaussian mixture model classification. Finally, the classification fusion rules are formulated based on expert experience and geological exploration data. Under the organic combination of survey data-driven and engineering geological knowledge guidance, a new set of high-precision classification and fusion methods is proposed for comprehensive geophysical exploration. By applying this new method to the karst exploration project in southern Zhejiang, a karst cave prediction is made with clearer boundaries. Compared with the actual drilling information, cave prediction and drilling information are highly consistent, which verifies the effectiveness of the method proposed.

BackgroundCancer remains a leading cause of mortality worldwide. A non-invasive screening solution was required for early diagnosis of cancer. Multi-cancer early detection (MCED) tests have been considered to address the challenge by simultaneously identifying multiple types of cancer within a single test using minimally invasive blood samples. However, a multi-cancer screening strategy utilizing urine-based metabolomics has not yet been developed.MethodsWe enrolled 911 cancer patients with 548 lung cancer (LC), 177 with gastric cancer (GC), and 186 with colorectal cancer (CRC), alongside 563 individuals with non-cancerous benign diseases and 229 healthy controls (HC) and investigated the metabolic profiles of urine samples. Participants were randomly allocated to discovery and validation cohorts. The discovery cohort was used for identifying multi-cancer and tissue-specific signatures to build the cancer screening and tumor origin prediction models, while the validation cohort was employed for assessing the performance of these models.ResultsWe identified and annotated a total of 360 metabolites from the urine samples. Using the LASSO regression algorithm, 18 metabolites were characterized as urinary metabolic biomarkers and exhibited excellent discriminative performance between cancer patients and HC with AUC of 0.96 in the validation cohort. In comparison with the performance of traditional tumor markers CEA, the screening model performed higher sensitivity across the cancer stages, with a particularly increase in sensitivity among early-stage cancer patients. Moreover, the screening model also exhibited in high classification of cancers from non-cancerous group, comprising with HC and benign disease participants. Furthermore, two non-overlapping metabolic panels were selected to differentiate LC from Non-LC and GC from CRC with the AUC values of 0.87 and 0.83 in validation cohorts, respectively. Additionally, the model accurately predicted the origin of three lethal cancers: lung, gastric, and colorectal, with an overall accuracy of 0.75. The AUC values for LC, GC, and CRC were 0.88, 0.88, and 0.80, respectively.DiscussionOur study demonstrates the potential of urine-based metabolomics for multi-cancer early detection. The approach offers non-invasive cancer screening, promising widespread implementation in population-based programs for early detection and improved outcomes. Further validation and expansion are needed for broader clinical applicability.

The conflicts stemming from discrepancies between human and artificial intelligence (AI) in observation, interpretation, and action have gained attention. Recent publications highlight the seriousness of the concern stemming from conflict and models to identify and assess the conflict risk. No work has been reported on systematically studying how to resolve human and artificial intelligence conflicts. This paper presents a novel approach to model the resolution strategies of human-AI conflicts. This approach reinterprets the conventional human conflict resolution mechanisms within AI. The study proposes a unique mathematical model to quantify conflict risks and delineate effective resolution strategies to minimize conflict risk. The proposed approach and mode are applied to control a two-phase separator system, a major component of a processing facility. The proposed approach promotes the development of robust AI systems with enhanced real-time responses to human inputs. It provides a platform to foster human-AI collaborative engagement and a mechanism of intelligence augmentation.

Abstract As a sensitive and non‐invasive method for assessing changes in renal cortical blood perfusion in the elderly, contrast‐enhanced ultrasound (CEUS) can indirectly reflect changes in kidney filtration and reabsorption function, thus providing feasibility for early evaluation of renal function changes. However, significant differences exist among researchers in terms of operational methods, contrast agent selection, post‐data analysis, and many other aspects, leading to substantial heterogeneity in results. This hinders horizontal comparisons and greatly limits the clinical application of contrast‐enhanced ultrasound for evaluating renal cortical blood flow perfusion. Based on the latest domestic and overseas literature and discussions with clinical experts, this consensus provides recommended guidelines for the evaluation of renal cortical blood flow perfusion using contrast‐enhanced ultrasound. It is hoped that this consensus will promote a better understanding of CEUS among medical practitioners at all levels and standardize the examination of renal cortical blood flow perfusion with CEUS.

Abstract Background The pathogenesis of diabetic cardiomyopathy is closely linked to abnormal glycosylation modifications. N-acetylglucosaminyltransferase V (GnT-V), which catalyzes the production of N-linked -1–6 branching of oligosaccharides, is involved in several pathophysiological mechanisms of many disorders, including cardiac hypertrophy and heart failure. However, the mechanism by which GnT-V regulates cardiac hypertrophy in diabetic cardiomyopathy is currently poorly understood. In this study, we investigated the role of GnT-V on myocardial hypertrophy in diabetic cardiomyopathy and elucidated the underlying mechanisms. Material and methods Streptozotocin (STZ) was intraperitoneally injected into mice to induce diabetic cardiomyopathy. An adeno-associated virus (AAV) carrying negative control small hairpin RNA (shNC) or GnT-V-specifc small hairpin RNA (shGnT-V) was used to manipulate GnT-V expression. In our study, forty male C57BL/6J mice were randomly divided into four groups (10 mice per group): control mice with AAV-shNC, diabetic cardiomyopathy mice with AAV-shNC, control mice with AAV-shGnT-V, and diabetic cardiomyopathy mice with AAV-shGnT-V. In addition, H9C2 cells and primary neonatal cardiac fibroblasts treated with high glucose were used as a cell model of diabetes. Analysis of cardiac hypertrophy and fibrosis, as well as functional studies, were used to investigate the underlying molecular pathways. Results AAV-mediated GnT-V silencing dramatically improved cardiac function and alleviated myocardial hypertrophy and fibrosis in diabetic mice. In vitro experiments demonstrated that GnT-V was elevated in cardiomyocytes and induced cardiomyocyte hypertrophy in response to high glucose stimulation. GnT-V knockdown significantly reduced the expression of the integrinβ1 signaling pathway, as evidenced by decreased downstream ERK1/2 activity, which inhibited cardiomyocyte hypertrophy accompanied by reduced ANP, BNP, and β-MHC expression. Furthermore, knocking down GnT-V expression lowered the TGF-β1-Smads signaling pathway, which reduced the expression of α-SMA, collagen I, and collagen III. Conclusions Overall, our research indicated that GnT-V may be a useful therapeutic target to treat diabetic cardiomyopathy, primarily in the inhibition of myocardial hypertrophy and fibrosis.

Subcooled flow boiling contains complex bubble behaviors and interactions. Accurate prediction and analysis of the subcooled flow boiling are of great significance for the safe operation and economy of the nuclear reactors. The bubble-layer-based model is a new theoretical model in predicting the flow boiling, which divides the flow filed into two regions in the radial direction, which are the bubble layer region and the core region. Bubble behaviors in each region, mass and energy exchanges between different regions, and variations of parameters in the axial direction are analyzed and reflected through a set of two-dimensional steady-state conservation equations of mass, momentum and energy. Therefore, this model can provide more detailed information of the flow field than current one-dimensional models. However, this bubble-layer-based model for the subcooled flow boiling has only been verified in conventional tubes. When the channel type and sizes change, the accuracy of the model is still uncertain. Considering that rectangular channels are widely encountered in multiphase flow equipment, this paper aims to further extend this model to the prediction of the subcooled flow boiling in rectangular channels. Firstly, several flow boiling experiments in both conventional rectangular channels and narrow rectangular channels were selected. The working conditions are 0.1-8 MPa for pressure, 211-1 700 kW/m2 for heat flux, 240-2 200 kg/(m2·s) for mass flux, 4.42×103-3.72×105 for liquid Reynold number and 0.83-1.76 for Prandtl number. Then, variations of void fraction obtained by this model were compared with these experimental data. The results show that this bubble-layer-based model shows high accuracy when it is applied to both conventional rectangular channels and narrow rectangular channels, which reflects that the channel size and shapes have limited impact on the accuracy of this model. In addition, to further verify the accuracy of this model, one of the existing models (Cai model) in predicting the void fraction in subcooled flow boiling was also selected for comparison. The results show that the bubble-layer-based model shows higher accuracy than Cai model, with the relative error of 32.7% and 52.6% respectively. Finally, this model was applied to the analysis of the flow boiling in one narrow rectangular channel. It describes the variations of several two-phase flow parameters, such as the void fraction, pressure, velocity and temperature. These results not only provide a better understanding of the mechanism of subcooled flow boiling, but also provide basic data for the thermal physical coupling analysis of the rectangular fuel elements in nuclear reactors.

Psoriasis is a chronic inflammatory disease characterized by increased keratinocyte proliferation and local inflammation. Long noncoding RNAs (lncRNAs) play important regulatory roles in many immune-mediated diseases, including psoriasis. In this study, we aimed to investigate the role and mechanism of lnc-SPRR2G-2 (SPRR2G) in M5-treated psoriatic keratinocytes.Fluorescence in situ hybridization and quantitative real-time polymerase chain reaction (qRT-PCR) showed that lnc-SPRR2G-2 was significantly upregulated in psoriasis tissues and psoriatic keratinocytes. In psoriatic keratinocytes, functional and molecular experiment analyses demonstrated that SPRR2G regulated proliferation, cell cycle and apoptosis, and induced the expression of S100 calcium binding protein A7 (S100A7), interleukin (IL)-1β, IL-8 and C-X-C motif chemokine ligand 10 (CXCL10). The function of SPRR2G in psoriasis is related to the STAT3 signaling pathway and can be inhibited by a STAT3 inhibitor. Moreover, KH-type splicing regulatory protein (KHSRP) was proved to be regulated by lnc-SPRR2G-2 and to control the mRNA decay of psoriasis-related cytokines (p

The grid-forming converters (GFMs) have been widely employed to support the power grid. Yet, the phase difference effect (PHE) caused by active power control (APC) on the system's design and stability is still inexplicable. This paper comprehensively investigates the PHE in the GFM under six APCs in terms of the developed impedance models. We observed that GFM exhibits nearly equal dq-frame impedance across six APCs when the PHE is disregarded. However, when accounting for PHE, the impedance of GFM with P-δ droop-based APCs differs significantly from that with P-ω droop- and virtual synchronous generator (VSG)-based APCs. Additionally, the sequence impedance of GFM with P-ω droop- and VSG-based APCs appears to be largely decoupled, whereas P-δ droop-based APCs introduce substantial sequence impedance coupling. Stability and coupling analyses indicate that the P-δ droop-based GFM must work in a weaker grid for stable operation compared to other APC-based GFM. Furthermore, the resulting frequency coupling leads to a higher amplitude of the coupled frequency (2f1-f) than the dominant frequency (f). Lastly, theoretical analysis is verified by experiments, providing new insights into the future research and design guidelines of GFM.

Intercropping systems can improve soil fertility and health, however, soil microbial communities and functional genes related to carbon, nitrogen and phosphorus cycling under the intercropping system of mesquite and perilla have not been studied. Therefore, in the present study, different planting densities and varieties of Perilla frutescens (L.) Britt and kiwifruit were used for intercropping, and changes in soil microbial communities and carbon, nitrogen, and phosphorus cycling genes in kiwifruit inter-roots under inter-cropping conditions were investigated by macro-genome sequencing technology. The results showed that intercropping with Perill caused a decrease in most soil nutrients, soil enzyme activities, and had a significant impact on the microbial (bacteria and fungi) diversity. Inter-cropping increased the relative abundance of the dominant bacterial phylum “Proteobacteria” and “Actinobacteria” by 47 and 57%, respectively, but decreased the relative abundance of the dominant fungal phylum “Chordata” and “Streptophyta” by 11 and 20%, respectively, in the inter-root soil of kiwifruit, and had a significant impact on the microbial (bacteria and fungi) diversity. In addition, inter-cropping could greatly increase the inter-root soil carbon sequestration (PccA, korA/B/C/D, fhs, and rbcl/s), carbon degradation (abfD), organic nitrogen mineralization (GDH2), denitrification (napA/B, nirB, norB), organic phosphorus mineralization (phop, phn), and inorganic phosphorus solubilization (gcd, ppk) gene abundance. The gene co-occurrence network indicated that soil korB, nirB, and gnd key functional genes for carbon, nitrogen, and phosphorus cycling in kiwifruit inter-root soils and their expression was up-regulated in the inter-cropping group. Structural equation (SEM) further showed that soil total nitrogen, organic matter, total carbon and acid phosphatase had significant effects on microbial diversity (p

Nasopharyngeal carcinoma (NPC) is a tumor of the head and neck, with a higher incidence in southern China and Southeast Asia. Radiotherapy and chemotherapy are the main treatments; however, metastasis and recurrence remain the main causes of treatment failure. Further, the majority of patients are diagnosed in the late stage due to lack of tumor-specific biomarker for early diagnosis. Therefore, an effective treatment and early detection can improve the outcome of patient with NPC. Axl and EGFR are co-expressed in NPC tissues and play key roles in tumor proliferation, migration, and invasion, which are often correlated with poor prognosis and therapy resistance. In this study, we generated a novel bispecific affibody (Z239-1907) for the dual targeting and inhibition of Axl and EGFR expression in NPC-positive cells both in vitro and in vivo. The in vitro experiments demonstrated that Z239-1907 had more pronounced antitumor effects than either modality alone (ZAXL239 or ZEGFR1907) in NPC-positive cells. Further, mice bearing NPC-positive tumors showed significant inhibition in tumor growth after treatment with Z239-1907 compared to ZAXL239 and ZEGFR1907. The in vivo tumor targeting ability and imaging also showed that Z239-1907 specifically and selectively targeted NPC xenograft mice models and accumulate at tumor site as early as 30 min and disappeared within 24 h post-injection. Collectively, these results suggest that Z239-1907 dual-target affibody is a promising therapeutic agent and a molecular imaging probe for early diagnosis in NPC.

Mycotoxins can enter and accumulate in the human body through contaminated foods, which is extremely harmful to human health. A rapid, sensitive, accurate and effective method is needed to detect mycotoxin contamination. With the advancement of science and technology, various types of biosensors have been continuously developed. Among them, magnetic and fluorescent sensors can produce sensitive and fast optical responses to the target compounds. This dual-function sensor has been widely used in the field of biological detection. This article reviews the application and future prospects of biosensors combining Fe3O4 magnetic nanoparticles with organic fluorescent materials, quantum dots, up-conversion nanoparticles, metal nanoclusters or fluorescent carbon nanomaterials in the detection of mycotoxins. This review is expected to provide a reference for further research and application of Fe3O4 magnetic and fluorescent sensors.

To analyze the reasons why tracheal diverticula is easy to be missed or misdiagnosed in the diagnosis and treatment of thyroid tumors, and to strengthen the understanding of the clinical characteristics of the disease. The reasons of the misdiagnosis and missed diagnosis in similar cases were analyzed, and the anatomy, differential diagnosis, and examination methods by reviewing the relevant literature in the past 20 years were further analyzed. At the same time, a retrospective analysis was carried out on two recent clinical cases of tracheal diverticula discovered during surgery. Tracheal diverticula is easily confused with thyroid tumor and may be misdiagnosed for the following reasons: tracheal diverticula is asymptomatic in most patients; symptomatic tracheal diverticula has similar clinical symptoms to thyroid nodules; lack of character in imaging findings. General surgeons should improve their awareness and vigilance of tracheal diverticula. Neck CT should be listed as a routine examination before thyroid-related surgery.

In order to study the hydration process of red clay cement grout prepared by red clay in the southwest Wumeng mountain area in southwest China and the micro-morphology of the grout stone, the hydration heat characteristics of red clay cement grout were measured by direct method, and the microstructure characteristics of the hydration products of red clay cement grout were analyzed by scanning electron microscope（ＳＥＭ）, and the effects of cement and structural additives on the hydration products of red clay cement grout were studied. According to the isothermal heat release curve of red clay cement slurry, the hydration process of red clay cement slurry can be divided into acceleration period, deceleration period and stability period, and the slurry hydration kinetics equation was obtained through regression analysis. The SEM pictures of the grout stone of red clay cement grout at different ages can be clearly observed: the skeleton structure at 3 d age was relatively fluffy, forming some small pieces of C-S-H gel; at the age of 7 d, a large amount of C-S-H gel was formed, and the stone body tended to form a whole. At 28 d age, the hydration products of the stone body had basically formed and overlapped with each other to form an overall structure. The research showed that cement is the basis of the hydration reaction for the red clay cement grout. The addition of structural additives improves the hydration reaction speed of cement, thus improves the early strength of grout.

Objective·To explore the characteristics and differences of gut microbiota in children with different severity of bronchial asthma, and build a prediction model of gut microbiota in severe asthma.Methods·In this study, children aged 5 to 14 diagnosed with asthma in the Department of Respiratory Medicine of Children's Hospital of Fudan University from Sep 1, 2020 to Aug 31, 2022 were selected, and children with severe asthma (SA) according to the Recommendations for Standardized Diagnosis and Management of Bronchial Asthma in Children (2020) were included. Children with mild to moderate asthma (MMA) and healthy children in the same period were matched according to age and gender. Stool samples collected from the three groups were subjected to 16S rRNA gene sequencing and the gut microbiota diversity, structure, and composition were assessed. The area under the receiver operating characteristic (ROC) curve (AUC) was applied to compare the predictive efficacy for SA.Results·Fifty children were enrolled in the SA group, 54 children matched by gender and age were in the MMA group and 39 healthy children were in the healthy control group. The α diversity of gut microbiota significantly decreased in the asthma children (P

Objective To report the diagnosis and treatment of a case of extraskeletal myxoid chondrosarcoma (EMC) in the pineal region misdiagnosed as chordoid glioma of the third ventricle, and to summarize the clinicopathological features, diagnosis and differential diagnosis of this rare tumor. Methods and Results A 42⁃year⁃old male patient with head MRI showed a space⁃occupying lesion in the pineal region and moderate enhancement on enhanced scan. After the first surgery, the histological morphology showed the boundary between tumor and brain tissue was not clear, spindle or stellate tumor cells were bunched, braided or scattered, the nuclei were small and deeply stained, and the interstitium was rich in collagen fibers and a large number of basophilic myxoid matrix. Immunohistochemical staining showed vimentin (Vim) expression in the cytoplasm of tumor cells, some of which expressed glial fibrillary acid protein (GFAP), CD34, CD99, but not cytokeratin (CK), epithelial membrane antigen (EMA) and S⁃100 protein (S⁃100). The pathological diagnosis was "chordoid glioma of the third ventricle". The tumor recurred 7 months after the first surgery, and the histological morphology of the second surgery showed obvious epithelioid features of the tumor cells, which were arranged in a cord, bundle or braided shape, with enlarged nuclei and easy to see mitotic images (up to 8/10 high magnification field). Some tumor cells were rich in cytoplasm and nuclear deviation, which were rhabdoid. The immunophenotype was the same as before, maintaining the diagnosis of "notochord glioma". The patient died of tumor progression 5 months after the second surgery. Combined with the literature, supplemental immunohistochemical staining showed that the tumor cells did not express Brachyury, thyroid transcription factor 1 (TTF⁃1), and SMARCB1/INI⁃1 proteins. Fluorescence in situ hybridization (FISH) test was positive for NR4A3 (9q22.33) gene rupture, and finally confirmed the diagnosis of EMC. Conclusions EMC in the pineal region is extremely rare, and attention should be paid to distinguishing it from the frequent mucinous tumors in the pineal region, such as chordoma, chordoid meningioma and chordoid glioma. Definite diagnosis depends on histological morphology, immunohistochemical staining and molecular detection.

Flow boiling is widely encountered in many industrial fields such as the steam generator in nuclear reactors. Nowadays, a lot of studies are focused on the bubble dynamics parameters due to the close relationship between the heat transfer and bubble behaviors. Bubble departure frequency is one of the important bubble dynamic parameters which reflects the bubble cycle in time and thus directly influences the bubble evaporation heat. In order to improve the predicting accuracy of bubble departure frequency and thus improve the accuracy of heat transfer calculation under flow boiling, the affecting factors of bubble departure frequency firstly through 13 groups of flow boiling independent experiments of water (506 experimental data points) were analyzed in this paper. It is found that bubble departure frequency decreases with the increasing of liquid subcooling, while it increases with the increasing of channel size, mass flux, wall superheating and pressure in which the effect of channel size is often ignored by many researchers. Then the accuracy of five existing prediction models was evaluated. The results show that none of them have high prediction accuracy in all experimental data points. Cole model and Zuber model both perform badly and have the absolute errors of 163.2% and 218.2% respectively and the relative errors of 134.2% and 205.1% respectively, because they only consider the effect of physical properties and thus they are more suitable for pool boiling. Brooks model and Basu model both overestimate the results with the absolute errors of 280.2% and 102.1% respectively and the relative errors of 2352% and 37.1% respectively. The reason lies in that these two models are developed through their own experiment data and thus have limited application ranges. Chen model performs relatively better with the absolute error of 64.8%, but it largely underestimates the results with the relative error of -52.3% for the reason that this model is developed based on the pool boiling experiments of methane and ignored the effects of mass flux and liquid subcooling. Besides, the results show that most predicting models perform badly when the channel size is small which confirm the significant influence of channel size. Therefore, in this paper, a new prediction model was developed with higher predicting accuracy through dimensionless analysis which consideres the effects of channel size, physical properties, wall superheating and mass flux. This new model has the mean absolute error of 39.2% and mean relative error of -14.3% with the application ranges of bubble Reynold number 28-2 303, Bond number 1-9.272 and Jakob number 0.004-0.049.

Photoelectrochemical cells (PECs) are an important technology for converting solar energy, which has experienced rapid development in recent decades. Transparent conductive oxides (TCOs) are also gaining increasing attention due to their crucial role in PEC reactions. This review comprehensively delves into the significance of TCO materials in PEC devices. Starting from an in-depth analysis of various TCO materials, this review discusses the properties, fabrication techniques, and challenges associated with these TCO materials. Next, we highlight several cost-effective, simple, and environmentally friendly methods, such as element doping, plasma treatment, hot isostatic pressing, and carbon nanotube modification, to enhance the transparency and conductivity of TCO materials. Despite significant progress in the development of TCO materials for PEC applications, we at last point out that the future research should focus on enhancing transparency and conductivity, formulating advanced theories to understand structure–property relationships, and integrating multiple modification strategies to further improve the performance of TCO materials in PEC devices.

BackgroundThe correlation between dietary vitamin B1 intake and cardiovascular diseases, as well as the all-cause and cardiovascular-associated mortality, is not well known. A large-scale data pool was used to examine the aforementioned correlations of Vitamin B1.MethodsThis paper analyzed the dietary data from the survey conducted by National Health and Nutrition Examination (NHANES; 1999–2018). The correlation of vitamin B1 intake in each quartile with cardiovascular diseases such as hypertension, coronary heart disease, myocardial infarction and heart failure was analyzed using multivariate logistic regression models. The hazard ratios for dietary vitamin B1 intake in each quartile, along with all-cause and cardiovascular-associated mortality, were performed using multivariate cox regression analysis, setting the lowest quartile (Q1) as a reference. The restricted cubic spline (RCS) method was used to study the nonlinear relationship. Subgroup stratification and sensitivity analyses were used to further investigate the association between them.ResultsThe study enrolled 27,958 subjects (with a mean follow-up time of 9.11 years). After multivariate adjustment, dietary vitamin B1 intake was significantly associated with hypertension, heart failure and cardiovascular mortality, with the most significant association in quartile 4 (Q4) of vitamin B1 intake. The results of the restricted cubic spline showed that vitamin B1 intake was nonlinearly associated with hypertension, whereas it was linearly associated with heart failure and cardiovascular mortality. Meanwhile, a dose–response correlation was observed, indicating that increased vitamin B1 intake leads to reduced risk of both cardiovascular prevalence and mortality. The stratified analysis showed that the correlation between age ≥ 50 years, overweight, smoking history, drinking history and dyslipidemia were more significant in male patients. The associations remained similar in the sensitivity analyses.ConclusionThe large NHANES-based studies indicate a gradual trend toward decreasing the risk of hypertension and heart failure prevalence and cardiovascular mortality with increasing dietary vitamin B1 intake. This association is especially significant in elderly-aged men, overweight individuals, smokers, drinkers, and dyslipidemia patients.

We discuss the implementation challenges of gas sensing systems based on low-frequency noise measurements on chemoresistive sensors. Resistance fluctuations in various gas sensing materials, in a frequency range typically up to a few kHz, can enhance gas sensing by considering its intensity and the slope of power spectral density. The issues of low-frequency noise measurements in resistive gas sensors, specifically in two-dimensional materials exhibiting gas-sensing properties, are considered. We present measurement setups and noise-processing methods for gas detection. The chemoresistive sensors show various DC resistances requiring different flicker noise measurement approaches. Separate noise measurement setups are used for resistances up to a few hundred kΩ and for resistances with much higher values. Noise measurements in highly resistive materials (e.g., MoS2, WS2, and ZrS3) are prone to external interferences but can be modulated using temperature or light irradiation for enhanced sensing. Therefore, such materials are of considerable interest for gas sensing.

Based on the background of “Industry-Academia-Research-Application” teaching integration, the teaching reform of Instrumental Analysis is the main research object, focusing on the reform and exploration from the aspects of teaching mechanism, teaching methodology, resource library construction, teaching team construction, teaching assessment and so on. It studies the construction mechanism of the integration of Industry-Academia-Research-Application of Instrumental Analysis; explores the specific implementation path of the integration, and researches the problems and characteristic innovations of the integration of Industry-Academia-Research and Application in the course of Instrumental Analysis.

The course of “Environmental Planning and Management” has been reformed and explored in terms of the preparation of course teaching programme and the implementation of teaching methodology, and Civic Education has been carried out throughout the whole process of teaching. Through the Civic Education of professional courses, students are guided to set up a correct world outlook, outlook on life and values, and to have the spirit of commitment to be the strivers of the new era. At the same time, we pay attention to the cultivation and inheritance of “craftsmanship” to achieve the goal of cultivating high-quality “moral and talent” application-oriented talents. This study provides reference for the cultivation of “new engineering" talents in polytechnic colleges and universities, and explores effective ways for the teaching reform of integrating “Civics of Courses” in the teaching of polytechnic professional courses according to the characteristics of Civics of Courses.

ABSTRACT The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been an unprecedented public health disaster in human history, and its spike (S) protein is the major target for vaccines and antiviral drug development. Although widespread vaccination has been well established, the viral gene is prone to rapid mutation, resulting in multiple global spread waves. Therefore, specific antivirals are needed urgently, especially those against variants. In this study, the domain of the receptor binding motif (RBM) and fusion peptide (FP) (amino acids [aa] 436 to 829; denoted RBMFP) of the SARS-CoV-2 S protein was expressed as a recombinant RBMFP protein in Escherichia coli and identified as being immunogenic and antigenically active. Then, the RBMFP proteins were used for phage display to screen the novel affibody. After prokaryotic expression and selection, four novel affibody molecules (Z14, Z149, Z171, and Z327) were obtained. Through surface plasmon resonance (SPR) and pseudovirus neutralization assay, we showed that affibody molecules specifically bind to the RBMFP protein with high affinity and neutralize against SARS-CoV-2 pseudovirus infection. Especially, Z14 and Z171 displayed strong neutralizing activities against Delta and Omicron variants. Molecular docking predicted that affibody molecule interaction sites with RBM overlapped with ACE2. Thus, the novel affibody molecules could be further developed as specific neutralization agents against SARS-CoV-2 variants. IMPORTANCE SARS-CoV-2 and its variants are threatening the whole world. Although a full dose of vaccine injection showed great preventive effects and monoclonal antibody reagents have also been used for a specific treatment, the global pandemic persists. So, developing new vaccines and specific agents are needed urgently. In this work, we expressed the recombinant RBMFP protein as an antigen, identified its antigenicity, and used it as an antigen for affibody phage-display selection. After the prokaryotic expression, the specific affibody molecules were obtained and tested for pseudovirus neutralization. Results showed that the serum antibody induced by RBMFP neutralized Omicron variants. The screened affibody molecules specifically bound the RBMFP of SARS-CoV-2 with high affinity and neutralized the Delta and Omicron pseudovirus in vitro. So, the RBMFP induced serum provides neutralizing effects against pseudovirus in vitro, and the affibodies have the potential to be developed into specific prophylactic agents for SARS-CoV-2 and its variants.

Nasopharyngeal carcinoma (NPC), is an Epstein-Barr virus (EBV) associated malignancy most common in Southern China and Southeast Asia. In southern China, it is one of the major causes of cancer-related death. Despite improvement in radiotherapy and chemotherapy techniques, locoregional recurrence and distant metastasis remains the major causes for failure of treatment in NPC patients. Therefore, finding new specific drug targets for treatment interventions are urgently needed. Here, we report three potential ZLMP1-C affibody molecules (ZLMP1-C15, ZLMP1-C114 and ZLMP1-C277) that showed specific binding interactions for recombinant and native EBV LMP1 as determined by epitope mapping, co-localization and co-immunoprecipitation assays. The ZLMP1-C affibody molecules exhibited high antitumor effects on EBV-positive NPC cell lines and displayed minimal cytotoxicity towards EBV-negative NPC cell line. Moreover, ZLMP1-C277 showed higher antitumor efficacy than ZLMP1-C15 and ZLMP1-C114 affibody molecules. The ability of ZLMP1-C277 decrease the phosphorylation levels of up-stream activator phospho-Raf-1(Ser338), phospho-MEK1/2(Ser217/Ser221), phospho-ERK1/2(Thr202/Thr204), thereby leading to downstream suppression of phospho-p90RSK(Ser380) and transcription factor c-Fos. Importantly, tumor growth was reduced in tumor-bearing mice treated with ZLMP1-C277 and caused no apparent toxicity. Taken together, our findings provide evidence that ZLMP1-C277 as a promising therapeutic agent in EBV-associated NPC.

ObjectivesMost studies have examined the association between serum copper and myocardial infarction, but there is little evidence of the association between dietary copper intake and myocardial infarction.Materials and methodsThe study included a total of 14,876 participants from the 2011 to 2018 National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression model was used to analyze the association between dietary copper intake and the risk of myocardial infarction. To reduce selection bias, we use nearest neighbor propensity score matching (PSM) in a 1:2 ratio. Restricted cubic spline (RCS) method is used to study the non-linear relationship. Subgroup stratification was used to further investigate the association between copper intake and myocardial infarction.ResultsThe median dietary copper intake was 1.0825 mg/day. A myocardial infarction had occurred in approximately 4.4% (655) of the participants. Before and after matching, multivariate logistic regression models revealed a negative correlation between dietary copper intake and the risk of myocardial infarction. The higher quartile of subjects had a noticeably lower risk of myocardial infarction in comparison to those in the first quartile of copper intake. According to RCS findings, dietary copper intake and myocardial infarction have a non-linear and dose-response relationship. According to stratified analysis, the dietary copper intake was a substantial protective element for those who were ≥ 50 years old, female, 25 ≤BMI

BackgroundThe risk of all-cause mortality in patients with heart failure (HF) has been studied previously. Readmission risk of HF patients was rarely explored. Thus, we aimed to explore early warning factors that may influence short-term readmission of HF patients.MethodsThe data of this study came from an HF database in China. It was a retrospective single-center observational study that collected characteristic data on Chinese HF patients by integrating electronic medical records and follow-up outcome data. Eventually, 1,727 patients with HF were finally included in our study.ResultsIn our study, the proportion of HF patients with New York Heart Association (NYHA) class II, III, and IV HF were 17.20%, 52.69%, and 30.11%, respectively. The proportion of patients with readmission within 6 months and readmission within 3 months was 38.33% and 24.20%, respectively. Multivariate logistic regression showed that NYHA class (pIII = 0.028, pIV < 0.001), diabetes (p = 0.002), Cr (p = 0.003), and RDW-SD (p = 0.039) were risk factors for readmission within 6 months of HF patients. NYHA class (pIII = 0.038, pIV < 0.001), CCI (p = 0.033), Cr (p = 0.012), UA (p = 0.042), and Na (p = 0.026) were risk factors for readmission within 3 months of HF patients.ConclusionsOur study implied risk factors of short-term readmission risk in patients with HF, which may provide policy guidance for the prognosis of patients with HF.

Background: The role of serum extracellular vesicles (EVs) is less known in psoriasis.Objectives: To explore the transcriptomic profile of serum EVs and the potential biomarkers in psoriasis.Methods: EVs were isolated by differential ultracentrifugation and identified by transmission electron microscope. The diameters of EVs were detected using nanoparticle tracking analysis. Serum EVs-keratinocyte interaction was observed through confocal fluorescence microscopy. miRNA microarray and mRNA microarray were performed in serum EVs (n = 4) and skin lesions (n = 3), respectively. Quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization were used to detect the expression of miRNAs in serum EVs and skin lesions (n = 15). Bioinformatics analysis was performed to predict the potential target genes and functions of miR-1305 and miR-6785-5p. Western blot, CCK-8 and enzyme-linked immunosorbent assay (ELISA) were used to detect the EVs’ biomarkers, keratinocytes proliferation and cytokines secretion.Results: A total of 16 miRNAs and 1,725 mRNAs were significantly dysregulated in serum EVs and skin lesions, respectively. miR-1305 was down-regulated and miR-6785-5p was upregulated in both serum EVs and skin lesions. Serum EVs could be taken up by keratinocytes. miR-1305 was downregulated and miR-6785-5p were upregulated in keratinocytes after co-cultured with psoriasis serum EVs compared with controls. Psoriasis serum EVs promoted keratinocyte proliferation and the secretion of CCL20 and IL-8. Serum EVs miR-1305 and miR-6785-5p were associated with disease severity.Conclusion: Serum EVs might be involved in the activation of keratinocytes through loaded miRNAs in psoriasis. Serum EVs miR-1305 and miR-6785-5p may be associated with psoriasis.

We propose and experimentally demonstrate high-speed operation of random-channel cryptography (RCC) in multimode fibers. RCC is a key generation and distribution method based on the random channel state of a multimode fiber and multi-dimension to single-dimension projection. The reciprocal intensity transmittance of the channel shared between the two legitimate users is used to generate and distribute correlated keys. In previous work, RCC's key rate-distance product was limited by the speed of light. In this work, we show that adding a fast modulator at one end of the channel decouples the key rate and distance, resulting in a significant improvement in the key rate-distance product, limited only by the fiber's modal dispersion. Error-free transmission at a key rate-distance product of 64.7 Mbps × 12 km, which is seven orders of magnitude higher than the previous demonstration, was achieved. The proposed method's security arises from a fundamental asymmetry between the eavesdroppers' and legitimate users' measurement complexity.

For the purpose of improving the service quality, video surveillance systems are widely used to standardize the service process in power supply business halls. If the employers check surveillance video to ensure predefined process of staff behaviours, it will be characterized as time-consuming. In recent years, great progress has been made in intelligent action recognition using Convolution Neural Networks (CNNs). However, due to the small range of staffs' motion and similar scene information of power supply business halls, the performance of using traditional CNNs to recognize service actions, e.g. bowing, standing and sitting, is general. For improving the recognition rate, this paper proposes a 3D-fused Convolutional Network (ConvNet) for service actions recognition, which focuses on detecting the actions in the typical scene of one staff person and one customer with a well-segmented video clip. The well-segmented video clips are sent as input to the 3D-fused ConvNet for action recognition. The 3D-fused ConvNet consists of two base learners, optical flow base learner and RGB base learner. Both learners use the Convolutional 3D (C3D) architecture. Specifically, the RGB learner can be used to capture the features of small staffs' motion while the optical flow base learner can be viewed as the key part to eliminate the influence of the background, especially in a similar scene. Furthermore, prediction scores of two base learners can be weighted by the softmax function according to the performance of each base learner. Finally, the prediction scores of the two base learners are fused to obtain the prediction result, namely the specific actions of the staffs in the videos. The experiment result shows that the proposed method achieves 92.41% accuracy on the service action dataset of the power supply business hall.

Background: The extensive involvement of interleukin enhancer binding factor 2 (ILF2) in RNA stability and the inflammatory response is well documented. Aberrant long noncoding RNA (lncRNA) expression contributes to the pathogenesis of psoriasis. However, little is known about the role of ILF2 in psoriasis.Objective: To investigate the role of ILF2 and KLHDC7B-DT in psoriasis.Methods: LncRNA expression in psoriatic tissues was measured by lncRNA microarray and qRT–PCR. Normal human epidermal keratinocytes (NHEKs), HaCaT cells, and Ker-CT cells stimulated with M5 (IL-17A, IL-22, IL-1α, oncostatin M, and TNF-α) were used to establish a psoriasis model in vitro. Fluorescence in situ hybridization was used to detect the distribution of KLHDC7B-DT and ILF2 in keratinocytes. The proliferative effects of KLHDC7B-DT and ILF2 on keratinocytes were demonstrated by EdU assay and flow cytometry. ELISA was used to detect the secretion levels of cytokines. RNA pull-down and RNA immunoprecipitation (RIP) were used to detect the direct binding of KLHDC7B-DT with ILF2. Western blotting was used to detect the proteins related to STAT3/JNK signalling pathways.Results: ILF2 and KLHDC7B-DT were significantly overexpressed in psoriatic tissues and M5-induced keratinocytes. KLHDC7B-DT promoted the proliferation of keratinocytes and induced the secretion of IL-6 and IL-8. KLHDC7B-DT could directly bind to ILF2 and activate the STAT3 and JNK signalling pathways. KLHDC7B-DT expression was regulated by ILF2. M5-induced proliferation and inflammatory cytokine secretion in keratinocytes was inhibited after ILF2 knockdown. Furthermore, we found that ILF2 promoted keratinocyte proliferation and the inflammatory response in a KLHDC7B-DT-dependent manner.Conclusions: ILF2 and KLHDC7B-DT are involved in the hyperproliferation of keratinocytes and skin inflammation in psoriasis. In addition, ILF2 functions in a KLHDC7B-DT-dependent manner.

BackgroundPrevious studies have shown that estrogen, kidney function, and homocysteine (Hcy) or hyperhomocysteinemia (HHcy) are related to each other. However, the underlying biological mechanisms still remain unclear. We aimed to explore the association between estradiol (E2) and HHcy in the female population, and to further evaluate the mediating role of renal function indicators.MethodsThis unmatched case–control study consisted of 1,044 female participants who were 60.60 ± 12.46 years old. Data on general demographic characteristics, such as age, smoking and drinking status, menopause and so on were collected in a personal interview, and laboratory examinations were performed by well-trained personnel. The mediating effect model was applied to analyze the direct and indirect effects of E2 on Hcy.ResultsThe average levels of Hcy and E2 of the participants were 12.6 μmol/L and 14.95 pg/ml. There were statistical differences in renal indexes blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA), glomerular filtration rate (GFR) and E2 between HHcy group and non-HHcy group. The logistic regression models showed that UA was risk factor for HHcy (P

Introduction: Chest computed tomography (CT) is important for the early screening of lung diseases and clinical diagnosis, particularly during the COVID-19 pandemic. We propose a method for classifying peripheral lung cancer and focal pneumonia on chest CT images and undertake 5 window settings to study the effect on the artificial intelligence processing results. Methods: A retrospective collection of CT images from 357 patients with peripheral lung cancer having solitary solid nodule or focal pneumonia with a solitary consolidation was applied. We segmented and aligned the lung parenchyma based on some morphological methods and cropped this region of the lung parenchyma with the minimum 3D bounding box. Using these 3D cropped volumes of all cases, we designed a 3D neural network to classify them into 2 categories. We also compared the classification results of the 3 physicians with different experience levels on the same dataset. Results: We conducted experiments using 5 window settings. After cropping and alignment based on an automatic preprocessing procedure, our neural network achieved an average classification accuracy of 91.596% under a 5-fold cross-validation in the full window, in which the area under the curve (AUC) was 0.946. The classification accuracy and AUC value were 90.48% and 0.957 for the junior physician, 94.96% and 0.989 for the intermediate physician, and 96.92% and 0.980 for the senior physician, respectively. After removing the error prediction, the accuracy improved significantly, reaching 98.79% in the self-defined window2. Conclusion: Using the proposed neural network, in separating peripheral lung cancer and focal pneumonia in chest CT data, we achieved an accuracy competitive to that of a junior physician. Through a data ablation study, the proposed 3D CNN can achieve a slightly higher accuracy compared with senior physicians in the same subset. The self-defined window2 was the best for data training and evaluation.

Sucrose phosphate synthase (SPS), a crucial rate-limiting enzyme that catalyzes the synthesis of precursors of sucrose, plays an indispensable role in the regulation of seed potato vigor. Nonetheless, the genes that encode SPS in potato have not undergone complete analysis, and the primary genes responsible for the regulation of seed potato vigor have not been screened and identified. In this study, four StSPS family members were identified by comparing the potato genome database with homologous proteins. Using bioinformatics, the physicochemical properties, subcellular localization, sequence structure, conserved motifs, and phylogenetics of StSPS were analyzed. The expression levels of StSPS in different potato tissues, from dormancy to sprouting in the seed potato tubers, were measured via qRT-PCR. The expression data from the potato genome database and previous transcriptome and proteome studies of dormancy to sprouting were also compared. After combining the analysis of SPS enzyme activity in diverse tuber tissues and the correlation analysis between multiple varieties with different dormancy periods and the expression of StSPS1, the primary gene StSPS1 that might regulate seed potato vigor was identified. This study set a theoretical and experimental groundwork for further verification and clarification of the regulatory function of StSPS1 in alterations in seed potato vigor.

The speed and direction of a missile shifts sharply in the dive phase, making the azimuth frequency modulation (FM) rate change with the azimuthal position, leading to azimuth ambiguities and image distortion. To solve this problem, a modified nonlinear chirp scaling (NLCS) algorithm was adopted to compensate for the azimuth FM rate. First, the geometric configuration and echo signal model of the spaceborne missile bistatic synthetic aperture radar (SAR) were built, and then the Doppler frequency correction was performed, and the 2-D spectrum of the signal was derived by the method of series reversion. Next, range migration correction and range compression were finished in the 2-D frequency domain. Following this, a modified NLCS algorithm was proposed to solve the space variance of Doppler phase problem. After compensating for the azimuth FM rate, the azimuth compression focusing was completed and the imaging result was obtained. Finally, by comparing the calculation amount, imaging effect, and performance index with the traditional NLCS algorithm, it can be concluded that the algorithm reduced the calculation amount by 1.0128 × 108 floating point operations per second (FLOPs) compared with the traditional NLCS algorithm, and the azimuth focusing effect of the edge point was greatly improved. Its resolution, peak sidelobe ratio (PSLR), and integrated sidelobe ratio (ISLR) were improved by 0.87 m, 3.32 dB, and 1.79 dB, respectively, which proved the effectiveness and feasibility of this method.

Multi-frequency signals have been accessible for most Global Navigation Satellite Systems . Existing studies have verified that using multi-frequency extra-wide-lane and wide-lane observations can realize decimeter, sub-decimeter and even centimeter rapid positioning. In this paper, a tightly combined wide-lane real-time kinematic positioning method using triple-frequency GPS and BDS is proposed. The differential inter-system bias is taken into consideration so that an inter-system differencing model is formed. Due to the influence of different frequencies between GPS and BDS, the double-difference wide-lane ambiguity between GPS and BDS reference satellites and the single-difference ambiguity of the BDS reference satellite are estimated jointly with the wide-lane differential inter-system bias. Thus, a full-rank model can be obtained without any external calibration. Using the stability of wide-lane differential inter-system bias in the estimation from epoch to epoch, redundant observations can be introduced, therefore the strength of the positioning model can be enhanced. Positioning performance under simulated obstructed environments is evaluated. The results show that the inter-system model can effectively improve the positioning compared with the conventional intra-system model for the severely obstructed situations.