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The playing field of a tennis competition is a dynamic and complex formative environment given the following preliminary knowledge: (a) the basic technical, tactical, situational, and special types of shots used by the opponent; (b) the hitting area of the tennis player; (c) the place of service; (d) the ball drop position; and (d) batting efficiency and other related information that may improve the chances of victory. In this study, we propose an AI classification model for tennis serve scores. Using a deep learning algorithm, the model automatically tracks and classifies the serve scores of professional tennis players from video data. We first defined the players’ techniques, volleys, and placements of strokes and serves. Subsequently, we defined the referee's tennis terms and the voice in deciding on a serve score. Finally, we developed a deep learning model to automatically classify the serving position, landing position, and use of tennis techniques. The methodology was applied in the context of 10 matches played by Roger Federer and Rafael Nadal. The proposed deep learning algorithm achieved a 98.27% accuracy in the automatic classification of serve scores, revealing that Nadal outscored Federer by 2.1% in terms of serve-scoring efficiency. These results are expected to facilitate the automatic comparison and classification of shots in future studies, enabling coaches to adjust tactics in a timely manner and thereby improve the chances of winning.

Controlling continuous cooling is an important means to control the most important mechanical properties of bainitic steel for frogs in railroad applications. In this paper, a bainitic steel for railway frogs is taken as the research object. By designing different cooling rates in the bainitic transformation medium temperature region, the effect of cooling rate on fatigue crack propagation rate was studied. The results show the sample of 4 °C/s cooling rate exhibits higher strength and impact toughness, while the crack propagation rate near the threshold is significantly lower and the threshold is relatively higher at 0.1 °C/s cooling rate. This is related to the fact that more massive blocky retained austenite and coarse microstructure in the sample at 0.1 °C/s cooling rate are more favorable to the occurrence of crack closure effect, especially in the near-threshold region. The fatigue crack propagation rate of the tested steel in the stable propagation region at 4 °C/s cooling rate is slightly higher than that at 0.1 °C/s. This is related to its complex interface distribution characteristics. However, with the increase of Δ K, the tested steel at 0.1 °C/s cooling rate tends to preferentially fail, which is related to its poor toughness.

Abstract Background In this study, we aimed to evaluate the clinical utility of Metagenomic Next-Generation sequencing (mNGS) on bronchoalveolar lavage fluid (BALF) in diagnosis of Lower Respiratory Tract Infections (LRTIs). Methods In this study, we retrospectively analyzed 186 hospitalized patients who were suspected with LRTIs and performed mNGS (DNA) test of BALF simultaneously at The Fifth Affiliated Hospital of Sun Yat-Sen University from March 2023 to August 2023. Suspected LRTI was based on LRTI related clinical manifestations or imaging examination. Among them, 155 patients had undergone conventional culture and mNGS (DNA) testing simultaneously. Finally, 138 cases (89.03%,138/155) were diagnosed as LRTI and 17 cases (10.97%,17/155) were diagnosed as non-LRTI. Both detecting rate and diagnostic efficacy of mNGS and conventional culture were compared. Results The positive detection rates of pathogens between mNGS and conventional culture were significant different (81.29% VS 39.35%, P 0.05). Furthermore, 77.54% and 35.51% of LRTI cases were being etiologically diagnosed by mNGS and culture respectively. Importantly, mNGS directly led to a change of treatment regimen in 58 (37.42%) cases, including antibiotic adjustment (29.68%) and ruling out active infection (7.74%). Moreover, treatment regimen remained unchanged in 97 (62.58%) cases, considering the current antibiotic therapy already covered the detected pathogens (36.13%) or empirical treatment was effective (11.61%). Conclusions mNGS can identify a wide range of pathogens in LRTIs, with improved sensitivity and being more superior at diagnosing LRTIs etiologically. mNGS has the potential to enhance clinical outcomes by optimizing the treatment regimens.

Abstract Background Plerocercoid larvae of the tapeworm Spirometra mansoni can infect both humans and animals, leading to severe parasitic zoonosis worldwide. Despite ongoing research efforts, our understanding of the developmental process of S. mansoni remains inadequate. To better characterize posttranslational regulation associated with parasite growth, development, and reproduction, a comparative phosphoproteomic study was conducted on the plerocercoid and adult stages of S. mansoni. Methods In this study, site-specific phosphoproteomic analysis was conducted via 4D label-free quantitative analysis technology to obtain primary information about the overall phosphorylation status of plerocercoids and adults. Results A total of 778 differentially abundant proteins (DAPs) were detected between adults and plerocercoids, of which 704 DAPs were upregulated and only 74 were downregulated. DAPs involved in metabolic activity were upregulated in plerocercoid larvae compared with adults, whereas DAPs associated with binding were upregulated in adults. Gene Ontology (GO) and Kyoto Encyclopedia of Genes (KEGG) analyses indicated that most DAPs involved in signal transduction and environmental information processing pathways were highly active in adults. DAPs upregulated in the plerocercoid group were enriched mainly in metabolic activities. The kinases PKACA, GSK3B, and smMLCK closely interact, suggesting potential active roles in the growth and development of S. mansoni. Conclusions The dataset presented in this study offers a valuable resource for forthcoming research on signaling pathways as well as new insights into functional studies on the molecular mechanisms of S. mansoni. Graphical abstract

Abstract Background The National Chest Pain Center Program (NCPCP) is a nationwide, quality enhancement program aimed at raising the standard of care for patients experiencing acute chest pain in China. The benefits of chest pain center (CPC) accreditation on acute coronary syndrome have been demonstrated. However, there is no evidence to indicate whether CPC accreditation improves outcomes for patients with acute aortic dissection (AAD). Methods We conducted a retrospective observational study of patients with AAD from 1671 hospitals in China, using data from the NCPCP spanning the period from January 1, 2016 to December 31, 2022. The patients were divided into 2 groups: pre-accreditation and post-accreditation admissions. The outcomes examined included in-hospital mortality, misdiagnosis, and Stanford type A AAD surgery. Multivariate logistic regression was employed to explore the relationship between CPC accreditation and in-hospital outcomes. Furthermore, we stratified the hospitals based on their geographical location (Eastern/Central/Western regions) or administrative status (provincial/non-provincial capital areas) to assess the impact of CPC accreditation on AAD patients across various regions. Results The analysis encompassed a total of 40,848 patients diagnosed with AAD. The post-accreditation group exhibited significantly lower rates of in-hospital mortality and misdiagnosis (12.1% vs. 16.3%, P

Abstract Metabolic dysfunction-associated steatohepatitis (MASH) poses challenges for targeted delivery and retention of therapeutic proteins due to excess extracellular matrix (ECM). Here we present a new approach to treat MASH, termed “Fibrosis overexpression and retention (FORT)”. In this strategy, we design (1) retinoid-derivative lipid nanoparticle (LNP) to enable enhanced mRNA overexpression in fibrotic regions, and (2) mRNA modifications which facilitate anchoring of therapeutic proteins in ECM. LNPs containing carboxyl-retinoids, rather than alcohol- or ester-retinoids, effectively deliver mRNA with over 10-fold enhancement of protein expression in fibrotic livers. The carboxyl-retinoid rearrangement on the LNP surface improves protein binding and membrane fusion. Therapeutic proteins are then engineered with an endogenous collagen-binding domain. These fusion proteins exhibit increased retention in fibrotic lesions and reduced systemic toxicity. In vivo, fibrosis-targeting LNPs encoding fusion proteins demonstrate superior therapeutic efficacy in three clinically relevant male-animal MASH models. This approach holds promise in fibrotic diseases unsuited for protein injection.

Abstract Background The built environment, as a critical factor influencing residents' cardiovascular health, has a significant potential impact on the incidence of cardiovascular diseases (CVDs). Methods Taking Xixiangtang District in Nanning City, Guangxi Zhuang Autonomous Region of China as a case study, we utilized the geographic location information of CVD patients, detailed road network data, and urban points of interest (POI) data. Kernel density estimation (KDE) and spatial autocorrelation analysis were specifically employed to identify the spatial distribution patterns, spatial clustering, and spatial correlations of built environment elements and diseases. The GeoDetector method (GDM) was used to assess the impact of environmental factors on diseases, and geographically weighted regression (GWR) analysis was adopted to reveal the spatial heterogeneity effect of environmental factors on CVD risk. Results The results indicate that the built environment elements and CVDs samples exhibit significant clustering characteristics in their spatial distribution, with a positive correlation between the distribution density of environmental elements and the incidence of CVDs (Moran’s I > 0, p

Abstract Ambidextrous search behaviors that jointly looking for technological and market knowledge gain attention in the innovation management literature. This study treats the ambidextrous search behaviors as a technology-market search paradox and examines the effect of organizational slack on the paradox and further explore whether this paradox has synergistic effects on performance in high-tech small medium-sized enterprises (SMEs). Besides, by integrating the literature of ambidextrous search and strategic management, we seek to understand the roles of strategic orientations, including growth-oriented and profit-oriented, in SMEs’ technology-market search paradox. Based on panel data of 547 high-tech SMEs, we find that organizational slack promotes both technology and market search, and ambidextrous search separately enhance high-tech SMEs’ performance, while the interaction of technology search and market search is negatively related to performance. Further, a growth-oriented strategy positively moderates the link between organizational slack and ambidextrous search and a profit-oriented strategy reinforces the relationship between organizational slack and technology search. We further enrich search-related and strategic literature.

Abstract Expressway networks are continuously developing and emergency rescue demand is increasing proportionately. The location of expressway emergency rescue nodes needs refinement to meet changing requirements. In this study, the expressway was modeled as an expressway network. The differences in the origin destination (OD) distribution matrices for working days and major holidays were used as the bases for determining the need for temporary emergency rescue nodes. Overlapping and non-overlapping community detection algorithms were used to extract the distribution characteristics of OD during both day categories. These distributions were used to determine permanent and temporary emergency rescue sites. In this study, we considered the differences in traffic volume, distance, and impact of four vehicle types on traffic accidents to select the location of emergency rescue nodes, and allocate emergency resources. An emergency rescue node selection model for an expressway network was established based on spatio-temporal characteristics. The results based on a regional example determined that 22 permanent and 25 temporary emergency rescue nodes were appropriate. The average rescue time for traffic accidents during working days and major holidays compared to the P-center location model, was reduced by approximately 27.08% and 6.70%, respectively. The coefficient of variation of emergency rescue time was reduced by approximately 28.22% and 21.41%, respectively. The results indicated that the model satisfied the expressway emergency rescue demand requirements, and improved the rationality of the rescue center node layout.

Abstract Background The relationship between periodontitis and cardiovascular disease (CVD) has been extensively studied, but the role of biological aging in this relationship remains poorly understood. This study is dedicated to investigating the effect of periodontitis on the incidence of CVD and to elucidating the potential mediating role of biological aging. Furthermore, this study will seek to elucidate the causal association between periodontitis, CVD, and biological aging. Methods We included 3269 participants from the National Health and Nutrition Examination Survey (2009–2014) with diagnostic information on periodontitis and composite CVD events. Biological aging was evaluated by utilizing both the Klemera–Doubal method’s calculated biological age (KDMAge) and phenotypic age (PhenoAge). Logistic regression, restricted cubic spline (RCS) analysis, and subgroup analysis were used for data analysis. Mediation analysis was employed to explore the mediating role of biological aging. Subsequently, Mendelian randomization (MR) analyses were performed using genome-wide association study databases to explore potential causal relationships between periodontitis, CVD, and biological aging. Results Periodontitis was associated with a higher risk of CVD. Participants with periodontitis were found to have increased levels of biological aging, and elevated levels of biological aging were associated with increased CVD risk. Mediation analyses showed a partial mediating effect of biological aging (PhenoAge: 44.6%; KDMAge: 22.9%) between periodontitis and CVD risk. MR analysis showed that periodontitis played a causal role in increasing the risk of small vessel stroke, while myocardial infarction was found to increase the risk of periodontitis. In addition, reverse MR analysis showed that phenotypic aging can increase the risk of periodontitis, and there is a two-way causal relationship between CVD and biological aging. Conclusions Periodontitis is associated with an increased CVD risk, partially mediated by biological aging, with a complex causal interrelationship. Targeted interventions for periodontal health may slow the biological aging processes and reduce CVD risk.

Abstract Background There are many options for the surgical treatment of pronation external rotation (PER) type IV ankle fractures, including the use of fibular plates and screws, the aim of this study was to investigate the biomechanical stability and safety of different internal fixation methods for PER type IV ankle fractures via finite element analysis. Methods A three-dimensional finite element model of the ankle joint and the whole foot of a healthy 26-years-old adult male was established and validated based on computed tomography images of his lower limb, and a computer-aided design was used to produce a PER type IV ankle fracture and plate and screw model. Four different internal fixation modes were simulated, including a (all ankle fixation—utilizing a fibular plate and screws for comprehensive stabilization of the ankle), b (inferior tibiofibular joint fixation + all ankle fixation), c (inferior tibiofibular joint fixation + unfixed anterior ankle), and d (inferior tibiofibular joint fixation + unfixed anterior and posterior ankles). The results of the four different fixation methods were compared via finite element analysis, and the von Mises stresses. The displacements of the four different fixation methods were analyzed as the output indices. Results There were no significant differences between the results of using fibular plates and screws and the displacement of fracture breaks among the four internal fixation modalities. The von Mises stress in the tibiotalar joint, median ankle, posterior ankle, and anterior ankle was minimized in the working condition of d, d, b, and d respectively. The von Mises stress in the fibular plate and screws was minimized in the working condition of a. The von Mises stress in the distal fibula was minimized in the working condition of a. However, the stress was mainly concentrated at the attachment point of the inferior tibiofibular anterior ligament, and in the working condition with inferior tibiofibular joint fixation, the stress was significantly concentrated in the inferior tibiofibular joint screw in all the fibular plates and screws. Conclusions The results of this study demonstrate the feasibility of using finite element analysis to compare the biomechanical stability and safety of four configurations of fibular plates and screws for treating PER type IV ankle fractures. All four modalities provided comparable biomechanical stability and safety, showing no significant differences. However, the current limitations of the finite element analysis methodology preclude specific clinical inferences. Further refinement of the methodology in future studies is necessary to enable reliable clinical applications.

Abstract Ischemic stroke poses significant challenges in terms of mortality and disability rates globally. A key obstacle to the successful treatment of ischemic stroke lies in the limited efficacy of administering therapeutic agents. Leveraging the unique properties of nanoparticles for brain targeting and crossing the blood–brain barrier, researchers have engineered diverse nanoparticle-based drug delivery systems to improve the therapeutic outcomes of ischemic stroke. This review provides a concise overview of the pathophysiological mechanisms implicated in ischemic stroke, encompassing oxidative stress, glutamate excitotoxicity, neuroinflammation, and cell death, to elucidate potential targets for nanoparticle-based drug delivery systems. Furthermore, the review outlines the classification of nanoparticle-based drug delivery systems according to these distinct physiological processes. This categorization aids in identifying the attributes and commonalities of nanoparticles that target specific pathophysiological pathways in ischemic stroke, thereby facilitating the advancement of nanomedicine development. The review discusses the potential benefits and existing challenges associated with employing nanoparticles in the treatment of ischemic stroke, offering new perspectives on designing efficacious nanoparticles to enhance ischemic stroke treatment outcomes. Graphical Abstract

Based on the production curves, changes in hydrocarbon composition and quantities over time, and production systems from key trial production wells in lacustrine shale oil areas in China, fine fraction cutting experiments and molecular dynamics numerical simulations were conducted to investigate the effects of changes in shale oil composition on macroscopic fluidity. The concept of “component flow” for shale oil was proposed, and the formation mechanism and conditions of component flow were discussed. The research reveals findings in four aspects. First, a miscible state of light, medium and heavy hydrocarbons form within micropores/nanopores of underground shale according to similarity and intermiscibility principles, which make components with poor fluidity suspended as molecular aggregates in light and medium hydrocarbon solvents, such as heavy hydrocarbons, thereby decreasing shale oil viscosity and enhancing fluidity and outflows. Second, small-molecule aromatic hydrocarbons act as carriers for component flow, and the higher the content of gaseous and light hydrocarbons, the more conducive it is to inhibit the formation of larger aggregates of heavy components such as resin and asphalt, thus increasing their plastic deformation ability and bringing about better component flow efficiency. Third, higher formation temperatures reduce the viscosity of heavy hydrocarbon components, such as wax, thereby improving their fluidity. Fourth, preservation conditions, formation energy, and production system play important roles in controlling the content of light hydrocarbon components, outflow rate, and forming stable “component flow”, which are crucial factors for the optimal compatibility and maximum flow rate of multi-component hydrocarbons in shale oil. The component flow of underground shale oil is significant for improving single-well production and the cumulative ultimate recovery of shale oil.

The classification and identification of species in Populus has remained a formidable challenge due to widespread interspecies hybridization. The complete chloroplast genome of Populus maximowiczii was obtained by Illumina high-throughput sequencing technology, with a typical quadripartite structure and 37.0% GC content. The chloroplast genome of P. maximowiczii was 156,892 in length, including a large single-copy region (LSC: 84,988 bp), a small single-copy region (SSC: 16,630 bp), and a pair of inverted repeats (IRs: each 27,637 bp in length). A total of 131 genes were annotated, including 86 protein-coding genes, 37 tRNAs, and 8 rRNAs. The phylogenetic analysis indicated that 43 species belonging to Populus were classified into monophyly, with P. cathayana being the closest relatives to P. maximowiczii. In conclusion, this study provides valuable insights into understanding the phylogeny of Populus.

Abstract In order to improve the measurement accuracy of mutual inductance parameters of transmission lines in the environment of double circuit power lines without power outage, this paper establishes simulation models for measuring mutual inductance parameters of transmission lines using the different frequency method in two modes: equal and unequal zero sequence self‐parameters of two circuit lines, using a parallel zero sequence coupling model of double circuit power lines. In the article, simulation analysis is conducted on the line parameters with a coupling coefficient between 0.4 and 0.6 and a line length of 20–50 km. In order to further verify the correctness of the simulation model and measurement methods, a test bench was established based on the principle of line mutual inductance parameter testing in a laboratory dual circuit line without a power outage environment for experimental testing. By comparing the test values under experimental conditions with the standard values, it has been proven that the model and method can meet the actual measurement requirements of engineering.

China is the world’s largest walnut producer, with an annual output of 4.795 9 million tons. Walnut kernels have high nutritional value, containing 65%−69% of oil and 15%−20% of protein. Walnut meal, an abundant byproduct of walnut oil production, is mainly used in animal feed and fertilizers with low processing efficiency, whose potential for high-value utilization is far from being excavated. Studies have found that walnut meal contains a large amount of protein (42%−54%), its amino acid composition is rich, and the proportion of amino acids in walnut meal is suitable for human absorption. Walnut meal is a source of high-quality plant protein with a true protein digestibility score of 86.22%, and a biological valence of 98.77%. Therefore, high-efficiency utilization of walnut meal proteins is an important pathway for the high-value utilization of walnut meal. In this article, the composition, structure, and nutritional value of walnut proteins are reviewed. The extraction methods and functional characteristics of walnut proteins are summarized. The effect of modification on their functionalities and digestibility is also summarized. Finally, the application potential of walnut protein in foods is discussed.

Abstract Objectives Hepatitis B is a liver disease caused by Hepatitis B virus (HBV) infection and is highly prevalent in China. To better understand the epidemiological characteristics of hepatitis B in China and develop effective disease control strategies, we employed temporal and spatial statistical methods. Methods We obtained HBV incidence data from the Public Health Science Data Center of the Chinese Center for Disease Control and Prevention for the years 2006 to 2018. Using Geographic Information System (GIS) and SaTScan scanning technology, we conducted spatial autocorrelation analysis and spatiotemporal scan analysis to create a map and visualize the distribution of hepatitis B incidence. Results While hepatitis B incidence rebounded in 2011 and 2017, the overall incidence in China decreased.In the trend analysis by item, the incidence varies from high to low. The global spatial autocorrelation analysis revealed a clustered distribution, and the Moran index analysis of spatial autocorrelation within local regions identified five provinces as H-H clusters (hot spots), while one province was an L-L cluster (cold spot). Spatial scan analysis identified 11 significant spatial clusters. Conclusions We found significant clustering in the spatial distribution of hepatitis B incidence and positive spatial correlation of hepatitis B incidence in China. We also identified high-risk times and regional clusters of hepatitis B incidence.

Abstract Background Madelung’s disease (MD), alternatively referred to as benign symmetric lipomatosis, multiple symmetric lipomatosis, or Launois–Bensaude syndrome, is an uncommon benign disorder marked by symmetric proliferation of adipose tissue in the head, neck, and torso regions. Case description In this case, the patient was a female with the late middle-aged demographic, diagnosed with Type I MD. Notably, she exhibited no prior history of alcohol consumption, and there was no family history of MD. Subsequent to the clinical diagnosis, the patient underwent medical imaging assessments to delineate the surgical parameters. Post-surgery, she demonstrated a favorable recovery trajectory, marked by the absence of any surgical complications. Result The patient underwent successful surgical excision of the lipomatous mass. Postoperatively, she had an uneventful recovery with no complications and no recurrence observed during the follow-up period of seven months. Conclusion Timely diagnosis and early surgical intervention play a pivotal role in enhancing the quality of life for individuals with MD. Preoperative medical imaging examinations function as highly effective tools, contributing to heightened surgical safety and a decreased probability of encountering complications during the surgical procedure.

Abstract Shrews being insectivores, serve as natural reservoirs for a wide array of zoonotic viruses, including the recently discovered Langya henipavirus (LayV) in China in 2018. It is crucial to understand the shrew-associated virome, viral diversity, and new viruses. In the current study, we conducted high-throughput sequencing on lung samples obtained from 398 shrews captured along the eastern coast of China, and characterized the high-depth virome of 6 common shrew species (Anourosorex squamipes, Crocidura lasiura, Crocidura shantungensis, Crocidura tanakae, Sorex caecutiens, and Suncus murinus). Our analysis revealed numerous shrew-associated viruses comprising 54 known viruses and 72 new viruses that significantly enhance our understanding of mammalian viruses. Notably, 34 identified viruses possess spillover-risk potential and six were human pathogenic viruses: LayV, influenza A virus (H5N6), rotavirus A, rabies virus, avian paramyxovirus 1, and rat hepatitis E virus. Moreover, ten previously unreported viruses in China were discovered, six among them have spillover-risk potential. Additionally, all 54 known viruses and 12 new viruses had the ability to cross species boundaries. Our data underscore the diversity of shrew-associated viruses and provide a foundation for further studies into tracing and predicting emerging infectious diseases originated from shrews.

Abstract Background Dendrobium Sw. represents one of the most expansive genera within the Orchidaceae family, renowned for its species’ high medicinal and ornamental value. In higher plants, the ankyrin (ANK) repeat protein family is characterized by a unique ANK repeat domain, integral to a plethora of biological functions and biochemical activities. The ANK gene family plays a pivotal role in various plant physiological processes, including stress responses, hormone signaling, and growth. Hence, investigating the ANK gene family and identifying disease-resistance genes in Dendrobium is of paramount importance. Results This research identified 78 ANK genes in Dendrobium officinale Kimura et Migo, 77 in Dendrobium nobile Lindl., and 58 in Dendrobium chrysotoxum Lindl. Subsequently, we conducted comprehensive bioinformatics analyses on these ANK gene families, encompassing gene classification, chromosomal localization, phylogenetic relationships, gene structure and motif characterization, cis-acting regulatory element identification, collinearity assessment, protein-protein interaction network construction, and gene expression profiling. Concurrently, three DoANK genes (DoANK14, DoANK19, and DoANK47) in D. officinale were discerned to indirectly activate the NPR1 transcription factor in the ETI system via SA, thereby modulating the expression of the antibacterial PR gene. Hormonal treatments with GA3 and ABA revealed that 17 and 8 genes were significantly up-regulated, while 4 and 8 genes were significantly down-regulated, respectively. DoANK32 was found to localize to the ArfGAP gene in the endocytosis pathway, impacting vesicle transport and the polar movement of auxin. Conclusion Our findings provide a robust framework for the taxonomic classification, evolutionary analysis, and functional prediction of Dendrobium ANK genes. The three highlighted ANK genes (DoANK14, DoANK19, and DoANK47) from D. officinale may prove valuable in disease resistance and stress response research. DoANK32 is implicated in the morphogenesis and development of D. officinale through its role in vesicular transport and auxin polarity, with subcellular localization studies confirming its presence in the nucleus and cell membrane. ANK genes displaying significant expression changes in response to hormonal treatments could play a crucial role in the hormonal response of D. officinale, potentially inhibiting its growth and development through the modulation of plant hormones such as GA3 and ABA.

Abstract Terbinafine, fluconazole, and amorolfine inhibit fungal ergosterol synthesis by acting on their target enzymes at different steps in the synthetic pathway, causing the accumulation of various intermediates. We found that the effects of these three in- hibitors on yeast morphology were different. The number of morphological parameters commonly altered by these drugs was only approximately 6% of the total. Using a rational strategy to find commonly changed parameters,we focused on hidden essential similarities in the phenotypes possibly due to decreased ergosterol levels. This resulted in higher apparent morphological similarity. Improvements in morphological similarity were observed even when canonical correlation analysis was used to select biologically meaningful morphological parameters related to gene function. In addition to changes in cell morphology, we also observed differences in the synergistic effects among the three inhibitors and in their fungicidal effects against pathogenic fungi possibly due to the accumulation of different intermediates. This study provided a comprehensive understanding of the properties of inhibitors acting in the same biosynthetic pathway.

Abstract Background In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR). Methods Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively. Results Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001). Conclusions Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications.

Abstract Histone lysine methyltransferase 2D (KMT2D) is the most frequently mutated epigenetic modifier in head and neck squamous cell carcinoma (HNSCC). However, the role of KMT2D in HNSCC tumorigenesis and whether its mutations confer any therapeutic vulnerabilities remain unknown. Here we show that KMT2D deficiency promotes HNSCC growth through increasing glycolysis. Additionally, KMT2D loss decreases the expression of Fanconi Anemia (FA)/BRCA pathway genes under glycolytic inhibition. Mechanistically, glycolytic inhibition facilitates the occupancy of KMT2D to the promoter/enhancer regions of FA genes. KMT2D loss reprograms the epigenomic landscapes of FA genes by transiting their promoter/enhancer states from active to inactive under glycolytic inhibition. Therefore, combining the glycolysis inhibitor 2-DG with DNA crosslinking agents or poly (ADP-ribose) polymerase (PARP) inhibitors preferentially inhibits tumor growth of KMT2D-deficient mouse HNSCC and patient-derived xenografts (PDXs) harboring KMT2D-inactivating mutations. These findings provide an epigenomic basis for developing targeted therapies for HNSCC patients with KMT2D-inactivating mutations.

Abstract Aiming to address the challenge where existing methods struggle to predict accurate disparities for imperfectly rectified stereo images, and that supervised training requires a considerable amount of ground truth, a self‐supervised binocular depth estimation algorithm with self‐rectification for autonomous driving is proposed. Firstly, a subnetwork dedicated to stereo rectification, aiming to estimate the homography between stereo images is developed. This homography facilitates the transformation of stereo image pairs, aligning their corresponding pixels horizontally. Secondly, a foundational self‐supervised framework primarily centred on minimizing errors in stereo image reconstruction, combined with the generative‐adversarial strategy is introduced. Finally, a vertical offset prediction module (VOPM) is incorporated into the basic framework to further enhance the resistance of the stereo matching network to pixel‐level vertical offset errors. Experimental results on the public KITTI dataset for autonomous driving demonstrate the effectiveness of this approach in improving the disparity prediction performance for imperfectly rectified stereo images. Moreover, the self‐supervised training framework exhibits superiority over state‐of‐the‐art methods.

Abstract The salient object detection task tries to simulate the human visual system for most eye‐catching objects or regions detection. However, due to the complexity of the visual mechanisms, current methods will suffer from severe performance degradation, leading to inconsistent prediction results for the same regions, when directly adopting a model trained on a fixed resolution to evaluate at other different resolutions. Considering that consistency in predictions is essential for salient object detection, a cross‐scale resolution consistent salient object detection method, called RCNet, is proposed. Specifically, to enhance the model's capacity for generalization across images of varying resolutions and make the model implicitly learn the scale invariance, a multi‐resolution data enhancement module is constructed to generate images with arbitrary resolutions for the same scene. Moreover, to accomplish better multi‐level feature fusion, a cross‐scale fusion module is developed to fuse high‐level semantic features and low‐level detail features. Additionally, to explicitly learn the scale invariance of the salient scores, a hybrid salient consistency loss is formulated on salient object detection with different resolutions. Comprehensive evaluations on five benchmark datasets show that RCNet achieves a highly competitive result.

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most destructive fungal diseases of wheat, and seriously threatens safe production of the crop worldwide. In China, new races historically appeared and rapidly developed to be predominant races and have resulted in ineffectiveness and replacement of wheat resistance cultivars as well as massive reduction in yield. In the present study, the relative parasitic fitness of the two newly-emerged Yr5-virulent races (TSA-6 and TSA-9) were compared with those of four currently predominant Chinese races (CYR31, CYR32, CYR33, and CYR34) based on evaluation on 10 Chinese wheat cultivars. As a result, there were significant differences in the relative parasitic fitness parameters among overall tested races based on multiple comparison (LSD) analysis (PTSA-9 (0.95)>TSA-6 (0.92)>CYR34 (0.29)>CYR31 (–1.54)>CYR33 (–1.77). The results indicated that two Yr5-virulent races TSA-9 and TSA-6 possessed relative parasitic fitness higher than races CYR34, CYR31, and CYR33, but lower than race CYR32, and have potential risks in developing to be predominant races. Therefore, continual monitoring of both Yr5-virulent races, and their variants is needed. The use of wheat cultivars (lines) with Yr5 resistance gene singly in wheat breeding is essential for being avoided, and is suggested to combine with other effective stripe rust resistance genes.

"Demand traction, technology promotion" is the main rule of the development of equipment system construction. This paper focuses on the analysis of system requirements, and puts forward the process of system requirements analysis on the basis of analyzing the basic connotation of system requirements analysis, combining the advantages of threat and capability; aiming at the key technical problems such as capability gap measurement and mapping analysis in system requirements analysis. The capacity gap measurement model is established, and the QFD method is used to realize the mapping between the capability requirement-system requirement-technology requirement, and the analysis of the typical space target monitoring system is taken as an example to verify the system demand analysis method proposed in this paper, which provides a theoretical basis for carrying out the system demand analysis.

Formaldehyde is an important carcinogen commonly found indoors. Its indoor sources have been intensively investigated. But study on outdoor formaldehyde concentration, which is potentially an important source to indoors, remains scarce. This study attempts to characterize temporal and spatial distribution of the atmospheric formaldehyde concentration in Chinese cities. Diurnal variation of ambient formaldehyde was examined in 6 cities and peak hours were identified between 12:00 pm and 3:00 pm. Consequently, outdoor formaldehyde concentrations were measured in the peak hours in 30 cities during the summer months of Jul.-Aug., 2022. The formaldehyde concentrations in the peak hours fell into a range of 0.005–0.087 mg/m3 (median value is 0.027 mg/m3), 87.7% of which have exceeded the chronic reference exposure criteria of 0.009 mg/m3 set by Office of Environmental Health Hazard Assessment. Health risk analysis suggests that exposure to ambient formaldehyde could cause a median carcinogenic risk of 1.9 × 10−5 (3.17×10−6–6.13×10−5), higher than threshold limit of 10−6. Pearson correlation analysis of the 30 cities shows that ambient summertime atmospheric formaldehyde concentrations of the city are positively correlated with its Gross Domestic Product (r = 0.48). We also found that the outdoor formaldehyde concentrations in urban areas (median: 0.017 mg/m3) is slightly higher than those in suburban areas (median: 0.013 mg/m3). Results here prove that outdoor formaldehyde is ubiquitous in Chinese cities and reduces effectiveness of ventilation in dilution indoor concentrations. Neglecting it would underestimate air cleaner capacity needed by a factor of about two. It should be accounted for in health analysis and air quality engineering control design of built environment in the future.

This paper presents a novel optimization model that explores the optimal investment strategies for DC pension plans with return of premium clauses. We have assumed that the financial market consists of a risk-free asset and a risky asset, where the price of the risky asset follows the CEV model. Under the expected utility criterion, the optimal investment strategies were derived by employing stochastic optimal control theory and the Legendre transformation method. Explicit expressions of the optimal investment strategy were provided when the utility function was specified as exponential, power, or logarithmic. Finally, numerical analysis was conducted to examine the impact of factors such as interest rate, return rate, and volatility of the risky asset on the optimal strategies.

Abstract The prevalence of non-small cell lung cancer (NSCLC) accounts for 85% of all lung cancers, with the Wnt/β-catenin signaling pathway exhibiting robust activation in this particular subtype. The expression of FAM83A (family with sequence similarity 83, member A) has been found to be significantly upregulated in lung cancer, leading to the stabilization of β-catenin and activation of the Wnt signaling pathway. In this study, we conducted a screening of down-regulated miRNAs in lung cancer with FAM83A as the target. Ultimately, we identified miR-1 as a negative regulator of FAM83A and confirmed that FAM83A is a direct target gene of miR-1 through dual luciferase reporter assays. The overexpression of miR-1 significantly attenuated the expression level of FAM83A and suppressed the Wnt signaling pathway, leading to a reduction in the expression levels of downstream target genes AXIN2, CyclinD1, and C-MYC. Additionally, it decreased the nuclear translocation of β-catenin. In addition, overexpression of miR-1 accelerated the degradation of β-catenin by inhibiting FAM83A, promoted the assembly of β-catenin degradation complex, and inhibited the proliferation, migration and invasion of NSCLC cells. In summary, miR-1 may be a potential candidate miRNA for the treatment of NSCLC.

Abstract Infection of piglets with Glaesserella parasuis (G. parasuis) induces host immunosuppression. However, the mechanism underlying the immunosuppression of piglets remains unclear. Activation of the PD-1/PD-L1 axis has been shown to trigger host immunosuppression. Baicalin possesses anti-inflammatory and immunomodulatory functions. However, whether baicalin inhibits PD-1/PD-L1 activation and thus alleviates host immunosuppression has not been investigated. In this study, the effect of baicalin on the attenuation of piglet immunosuppression induced by G. parasuis was evaluated. Seventy piglets were randomly divided into the control group, infection group, levamisole group, BMS-1 group, 25 mg/kg baicalin group, 50 mg/kg baicalin group and 100 mg/kg baicalin group. Following pretreatment with levamisole, BMS-1 or baicalin, the piglets were challenged with 1 × 108 CFU of G. parasuis. Our results showed that baicalin, levamisole and BMS-1 modified routine blood indicators and biochemical parameters; downregulated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA expression; and upregulated IL-2 and IL-8 mRNA expression in blood. Baicalin, levamisole and BMS-1 increased the proportions of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD3–CD21+ B cells in the splenocyte population, increased the proportions of CD3+ T cells, CD3+CD4+ T cells and CD3+CD8+ T cells in the blood, and inhibited PD-1/PD-L1 and TIM-3 activation. Baicalin, levamisole and BMS-1 reduced p-PI3K, p-Akt, and p-mTOR expression, the p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 ratios and increased RAS expression. Baicalin, levamisole and BMS-1 provided substantial protection against G. parasuis challenge and relieved tissue histopathological damage. Our findings might provide new strategies for controlling G. parasuis infection and other immunosuppressive diseases.

Abstract Glaesserella parasuis (G. parasuis) induces vascular damage and systemic inflammation. However, the mechanism by which it causes vascular damage is currently unclear. Baicalin has important anti-inflammatory, antibacterial and immunomodulatory functions. In this study, we explored the ability of baicalin and probenecid to protect against G. parasuis challenge in a piglet model. Sixty piglets were randomly divided into a control group; an infection group; a probenecid group; and 25 mg/kg, 50 mg/kg and 100 mg/kg baicalin groups. The probenecid group and the 25 mg/kg, 50 mg/kg and 100 mg/kg baicalin groups were injected intramuscularly with 20 mg/kg body weight (BW) probenecid and 25 mg/kg BW, 50 mg/kg BW and 100 mg/kg BW baicalin, respectively. All piglets except those from the control group were injected intraperitoneally with 1 × 108 CFU of G. parasuis. The control group was injected intraperitoneally with TSB. The results showed baicalin and probenecid protected piglets against G. parasuis challenge, improved body weight and decreased temperature changes in piglets. Baicalin and probenecid attenuated IL-1β, IL-10, IL-18, TNF-α and IFN-γ mRNA levels in the blood for 48 h, inhibited the production of the nucleosides ATP, ADP, AMP and UMP from 24 to 72 h, reduced Panx-1/P2Y6/P2X7 expression, weakened NF-kB, AP-1, NLRP3/Caspase-1 and ROCK/MLCK/MLC signalling activation, and upregulated VE-cadherin expression in the blood vessels of piglets challenged with G. parasuis. Baicalin and probenecid alleviated pathological tissue damage in piglets induced by G. parasuis. Our results might provide a promising strategy to control and treat G. parasuis infection in the clinical setting.

This study aims to investigate the phase composition, microstructure, and mechanical properties of three refractory high-entropy alloys (RHEAs): Al7(NbTiZr)93, Al7(NbTiZrMo)93, and Al7(NbTiZrTa)93. The as-cast Al7(NbTiZr)93 alloy exhibits a single-phase BCC structure, with a yield strength (YS) of 1050 MPa at room temperature. The addition of Mo and Ta leads to the formation of Al7(NbTiZrMo)93 and Al7(NbTiZrTa)93 alloys with BCC-B2 and B2-FCC dual-phase structures, whose YS values reach 1741 MPa and 2350 MPa, respectively. At 800 °C, trace amounts of ordered B2 phase are generated in the Al7(NbTiZr)93 matrix, and the YS decreases from 1050 MPa at room temperature to 219 MPa at 800 °C. In the Al7(NbTiZrMo)93 alloy, the 10 nm B2 precipitates grow to several hundred nanometers, and the YS decreases to 431 MPa after compression at 800 °C. In the Al7(NbTiZrTa)93 alloy, the grid B2-FCC structure at room temperature transforms into a disordered BCC structure at 800 °C, yet possessing the YS of 908 MPa and demonstrating acceptable ductility. Moreover, Ta exhibits the better structural and performance matching than Mo in AlNbTiZr-based RHEAs. Therefore, it opens up new prospects for regulating the structure and high-temperature performance of AlNbTiZr-based RHEAs.

The deformation behavior of the pure aluminum has been studied at 298 K and 77 K to elucidate the mechanism for dual-enhancement effect at cryogenic temperature. The results reveal that as the deformation temperature decreases from 298 K to 77 K, the tensile strength and elongation increase from 67.9 MPa to 49.1% to 142.4 MPa and 61.9%, respectively. The simultaneous increase in strength and ductility at 77 K is attributed to the higher strain hardening rate and more uniform deformation at cryogenic temperature. Results obtained from quasi in-situ EBSD indicate that at cryogenic temperatures, there is a higher density of dislocations that are uniformly distributed within the grains. It helps alleviate dislocation pile-ups and reduces the likelihood of crack initiation at grain boundaries. Moreover, a significant number of grains align their orientation rotation towards at cryogenic temperature. Multiple fine slip systems initiate within these grains, contributing to improved mechanical properties in pure aluminum. In contrast, samples deformed at 298 K exhibit localized strain during deformation, with the initiation of unfavorable, non-uniform coarse slip bands within the grains. The findings of this study offer insights into the mechanisms of the dual-enhancement effect in pure aluminum at cryogenic temperatures.

Effects of different concentrations of biogas slurry (BS) were evaluated relative to vegetable cultivation. Five concentration levels of BS were used as organic fertilizer to grow Chinese cabbages (CA) by drip irrigation to study the effect of BS on the yield and quality. Each level was replicated three times and BS was used seven times. Results showed that the average plant height, fresh weight, dry weight, and soluble sugars and protein contents of Chinese cabbage under the T1 (BS 25%) treatment were optimal. Among them, dry weight per plant (3.53g), soluble sugar content (0.41%), and soluble protein content (0.0039%) were 1.74 times, 1.41 times, and 1.14 times more than under the CK treatment, respectively. In addition, the application of biogas slurry improved the physical and chemical properties of soil. Soil total nitrogen (TN) and available phosphorus (AP) content increased after the use of biogas slurry, and the soil total nitrogen and available phosphorus content increased with the increase in the concentration of the applied biogas slurry. The available potassium (AK) content of soil fluctuated with the concentration of biogas slurry. In addition, biogas slurry can properly improve soil pH. In conclusion, BS 25% was the best for the growth of CA and its quality, which provided scientific basis for biogas slurry as fertilizer.

Abstract Chemical molecular structures are a direct and convenient means of expressing chemical knowledge, playing a vital role in academic communication. In chemistry, hand drawing is a common task for students and researchers. If we can convert hand-drawn chemical molecular structures into machine-readable formats, like SMILES encoding, computers can efficiently process and analyze these structures, significantly enhancing the efficiency of chemical research. Furthermore, with the progress of educational technology, automated grading is gaining popularity. When machines automatically recognize chemical molecular structures and assess the correctness of the drawings, it offers great convenience to teachers. We created ChemReco, a tool designed to identify chemical molecular structures involving three atoms: C, H, and O, providing convenience for chemical researchers. Currently, there are limited studies on hand-drawn chemical molecular structures. Therefore, the primary focus of this paper is constructing datasets. We propose a synthetic image method to rapidly generate images resembling hand-drawn chemical molecular structures, enhancing dataset acquisition efficiency. Regarding model selection, the hand-drawn chemical molecule structural recognition model developed in this article achieves a final recognition accuracy of 96.90%. This model employs the encoder-decoder architecture of EfficientNet + Transformer, demonstrating superior performance compared to other encoder-decoder combinations.

Abstract Many DNA viruses develop various strategies to inhibit cell death to facilitate their replication. However, whether influenza A virus (IAV), a fast-replicating RNA virus, attenuates cell death remains unknown. Here, we report that IAV infection induces TAK1 phosphorylation in a murine alveolar epithelial cell line (LET1) and a murine fibroblastoma cell line (L929). The TAK1-specific inhibitor 5Z-7-Oxzeneonal (5Z) and TAK1 knockout significantly enhance IAV-induced apoptosis, as evidenced by increased PARP, caspase-8, and caspase-3 cleavage. TAK1 inhibition also increases necroptosis as evidenced by increased RIPK1S166, RIPK3T231/S232, and MLKLS345 phosphorylation. Mechanistically, TAK1 activates IKK, which phosphorylates RIPK1S25 and inhibits its activation. TAK1 also activates p38 and its downstream kinase MK2, which phosphorylates RIPK1S321 but does not affect RIPK1 activation. Further investigation revealed that the RIPK1 inhibitor Nec-1 and RIPK1 knockout abrogate IAV-induced apoptosis and necroptosis; re-expression of wild-type but not kinase-dead (KD)-RIPK1 restores IAV-induced cell death. ZBP1 knockout abrogates IAV-induced cell death, whereas RIPK3 knockout inhibits IAV-induced necroptosis but not apoptosis. 5Z treatment enhances IAV-induced cell death and slightly reduces the inflammatory response in the lungs of H1N1 virus-infected mice and prolongs the survival of IAV-infected mice. Our study provides evidence that IAV activates TAK1 to suppress RIPK1-dependent apoptosis and necroptosis, and that RIPK3 is required for IAV-induced necroptosis but not apoptosis in epithelial cells.

Abstract The tumor microenvironment (TME) plays a pivotal role in the onset, progression, and treatment response of cancer. Among the various components of the TME, cancer-associated fibroblasts (CAFs) are key regulators of both immune and non-immune cellular functions. Leveraging single-cell RNA sequencing (scRNA) data, we have uncovered previously hidden and promising roles within this specific CAF subgroup, paving the way for its clinical application. However, several critical questions persist, primarily stemming from the heterogeneous nature of CAFs and the use of different fibroblast markers in various sample analyses, causing confusion and hindrance in their clinical implementation. In this groundbreaking study, we have systematically screened multiple databases to identify the most robust marker for distinguishing CAFs in lung cancer, with a particular focus on their potential use in early diagnosis, staging, and treatment response evaluation. Our investigation revealed that COL1A1, COL1A2, FAP, and PDGFRA are effective markers for characterizing CAF subgroups in most lung adenocarcinoma datasets. Through comprehensive analysis of treatment responses, we determined that COL1A1 stands out as the most effective indicator among all CAF markers. COL1A1 not only deciphers the TME signatures related to CAFs but also demonstrates a highly sensitive and specific correlation with treatment responses and multiple survival outcomes. For the first time, we have unveiled the distinct roles played by clusters of CAF markers in differentiating various TME groups. Our findings confirm the sensitive and unique contributions of CAFs to the responses of multiple lung cancer therapies. These insights significantly enhance our understanding of TME functions and drive the translational application of extensive scRNA sequence results. COL1A1 emerges as the most sensitive and specific marker for defining CAF subgroups in scRNA analysis. The CAF ratios represented by COL1A1 can potentially serve as a reliable predictor of treatment responses in clinical practice, thus providing valuable insights into the influential roles of TME components. This research marks a crucial step forward in revolutionizing our approach to cancer diagnosis and treatment.

Abstract Decellularized extracellular matrix hydrogel (ECM hydrogel), a natural material derived from normal tissue with unique biocompatibility properties, is widely used for tissue repair. However, there are still problems such as poor biological activity and insufficient antimicrobial property. To overcome these drawbacks, fibroblast growth factor 2 (FGF 2) containing exosome (exoFGF 2) was prepared to increase the biological activity. Furthermore, the antimicrobial capacity of ECM hydrogel was optimised by using copper ions as a ligand-bonded cross-linking agent. The decellularized extracellular matrix hydrogel, intricately cross-linked with copper ions through ligand bonds and loaded with FGF 2 containing exosome (exoFGF 2@ECM/Cu2+ hydrogel), has demonstrated exceptional biocompatibility and antimicrobial properties. In vitro, exoFGF 2@ECM/Cu2+ hydrogel effectively promoted cell proliferation, migration, antioxidant and inhibited bacterial growth. In vivo, the wound area of rat treated with exoFGF 2@ECM/Cu2+ hydrogels were significantly smaller than that of other groups at Day 5 (45.24% ± 3.15%), Day 10 (92.20% ± 2.31%) and Day 15 (95.22% ± 1.28%). Histological examination showed that exoFGF 2@ECM/Cu2+ hydrogels promoted angiogenesis and collagen deposition. Overall, this hydrogel has the potential to inhibit bacterial growth and effectively promote wound healing in a variety of clinical applications.

Abstract Background Breast cancer (BC) is a heterogeneous disease, with the ductal subtype exhibiting significant cellular diversity that influences prognosis and response to treatment. Single-cell RNA sequencing data from the GEO database were utilized in this study to investigate the underlying mechanisms of cellular heterogeneity and to identify potential prognostic markers and therapeutic targets. Methods Bioinformatics analysis was conducted using R packages to analyze the single-cell sequencing data. The presence of highly variable genes and differences in malignant potency within the same BC samples were examined. Differential gene expression and biological function between Type 1 and Type 2 ductal epithelial cells were identified. Lasso regression and Cox proportional hazards regression analyses were employed to identify genes associated with patient prognosis. Experimental validation was performed in vitro and in vivo to confirm the functional relevance of the identified genes. Results The analysis revealed notable heterogeneity among BC cells, with the presence of highly variable genes and differences in malignant behavior within the same samples. Significant disparities in gene expression and biological function were identified between Type 1 and Type 2 ductal epithelial cells. Through regression analyses, CYP24A1 and TFPI2 were identified as pivotal genes associated with patient prognosis. Kaplan-Meier curves demonstrated their prognostic significance, and experimental validation confirmed their inhibitory effects on malignant behaviors of ductal BC cells. Conclusion This study highlights the cellular heterogeneity in ductal subtype breast cancer and delineates the differential gene expressions and biological functions between Type 1 and Type 2 ductal epithelial cells. The genes CYP24A1 and TFPI2 emerged as promising prognostic markers and therapeutic targets, exhibiting inhibitory effects on BC cell malignancy in vitro and in vivo. These findings offer the potential for improved BC management and the development of targeted treatment strategies.

Abstract Background This study investigated the molecular mechanism of long intergenic non-protein coding RNA 1605 (LINC01605) in the process of tumor growth and liver metastasis of pancreatic ductal adenocarcinoma (PDAC). Methods LINC01605 was filtered out with specificity through TCGA datasets (related to DFS) and our RNA-sequencing data of PDAC tissue samples from Renji Hospital. The expression level and clinical relevance of LINC01605 were then verified in clinical cohorts and samples by immunohistochemical staining assay and survival analysis. Loss- and gain-of-function experiments were performed to estimate the regulatory effects of LINC01605 in vitro. RNA-seq of LINC01605-knockdown PDAC cells and subsequent inhibitor-based cellular function, western blotting, immunofluorescence and rescue experiments were conducted to explore the mechanisms by which LINC01605 regulates the behaviors of PDAC tumor cells. Subcutaneous xenograft models and intrasplenic liver metastasis models were employed to study its role in PDAC tumor growth and liver metastasis in vivo. Results LINC01605 expression is upregulated in both PDAC primary tumor and liver metastasis tissues and correlates with poor clinical prognosis. Loss and gain of function experiments in cells demonstrated that LINC01605 promotes the proliferation and migration of PDAC cells in vitro. In subsequent verification experiments, we found that LINC01605 contributes to PDAC progression through cholesterol metabolism regulation in a LIN28B-interacting manner by activating the mTOR signaling pathway. Furthermore, the animal models showed that LINC01605 facilitates the proliferation and metastatic invasion of PDAC cells in vivo. Conclusions Our results indicate that the upregulated lncRNA LINC01605 promotes PDAC tumor cell proliferation and migration by regulating cholesterol metabolism via activation of the mTOR signaling pathway in a LIN28B-interacting manner. These findings provide new insight into the role of LINC01605 in PDAC tumor growth and liver metastasis as well as its value for clinical approaches as a metabolic therapeutic target in PDAC.

Abstract On-line monitoring of flow rate is rather important to evaluate the water consumption of the pump-turbine and the overall efficiency of the pumped storage station. Flow rate can be worked out based on the flow differential pressure measured in the flow passage and coefficients determined on model test. But the coefficients must be calibrated to obtain the reliable flow rate. As thermodynamic method is a common way to measure the discharge of prototype pump-turbine, site test is carried out on a vertical pump-turbine with 600 m rated head to calibrated the coefficients in this paper. Measuring devices are designed to satisfy both the turbine and pump operating conditions, and test results of flow rate at both turbine and pump operating conditions are presented and show that the calibrated coefficients are different to the predicted values. The calibrated results indicate the importance of site calibration on prototype turbine to ensure the monitoring validity on real-time flow rate.

Abstract In order to study the effect of the velocity pulse on the dynamic response of the train-bridge system of the high-speed railway simple supported beam bridge, the velocity pulse is simulated by the trigonometric function method and superimposed with the far-field earthquake without pulse to synthesize the pulse with different pulse types, pulse periods and pulse peaks. A 10 $$\times$$ × 32m typical high-speed railway simple supported beam bridge is considered an case illustrating study. Then, the dynamic response of train-track-bridge coupling system is calculated by train-track-bridge seismic analysis software TTBSAS. Afterwards, the influence of pulse near-field earthquakes parameters and vertical components on dynamic response of train-bridge system and the safety of the train on the bridge are discussed in detail.The new derailment evaluation index is adopted to evaluate driving safety under earthquakes. The train safety control of simply supported beam bridge under the action of near-field earthquake is studied. The results show that the impact of pulse ground motion on the dynamic response of the train-track-bridge coupling system is significantly higher than that of no-pulse ground motion, especially the impact on the bridge and rail subsystem is more significant than that of train subsystem. Under the excitation of ground motion intensity of 0.05g $$\sim$$ ∼ 0.15g, the safe speed threshold of pulse near-field ground motion is smaller than that of far-field ground motion. When the ground motion intensity is 0.20g $$\sim$$ ∼ 0.30g, the safe speed threshold of pulse near-field ground motion and far field ground motion is 200km/h. So, the pulse near-field earthquake poses a greater threat to the safety of the train on the bridge than the far-field earthquake. Therefore, the influence of pulse near-field earthquakes should be considered in the seismic design. The research results of this paper can provide theoretitcal support for the design of a high-speed railway bridge in the near-field area.

Abstract Independent controls of various properties of electromagnetic (EM) waves are crucially required in a wide range of applications. Programmable metasurface is a promising candidate to provide an advanced platform for manipulating EM waves. Here, we propose an approach that can arbitrarily control the polarization direction and phases of reflected waves in linear and nonlinear ways using a stacked programmable metasurface. Further, we extend the space-time-coding theory to incorporate the dimension of polarization, which provides an extra degree of freedom for manipulating EM waves. As proof-of-principle application examples, we consider polarization rotation, phase manipulation, and beam steering at linear and nonlinear frequencies. For validation, we design, fabricate, and measure a metasurface sample. The experimental results show good agreement with theoretical predictions and simulations. The proposed approach has a wide range of applications in various areas, such as imaging, data storage, and wireless communication.