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Abstract Fish diversity, an important indicator of aquatic ecosystem health, is declining due to water pollution, overfishing, climate change, and invasive species. Effective surveying and monitoring are required to protect fish diversity. Here, a high-sensitivity environmental DNA (eDNA) metabarcoding technique was used to investigate fish diversity in the Danjiang River, Shaanxi Province, China. In total, 59 species were identified in eight orders, 19 families, and 40 genera. Cypriniformes and Perciformes were the main groups in the survey area, while Cyprinidae accounted for 50.85% of the total fish species. Rhinogobius similis (19%), Hemibarbus umbrifer (11%), Gnathopogon herzensteini (10%), Triplophysa stewarti (8%), and Zacco platypus (7%) were the dominant species. Eight rare and two exotic fish species were identified. Combined with analysis of historical data, the richness of fish identified using eDNA metabarcoding was significantly higher than that of fish captured in ground cages. Temperature, pH, and oxidation-reduction potential are the main environmental factors that affect the spatial distribution of fish communities. These results suggest that eDNA metabarcoding could be a new tool with broad application prospects; however, local databases must be improved. This study provides theoretical data and a methodological reference for protecting and managing fish diversity in the Qinling Mountains.

In urban smart city environments, traffic hazards can lead to catastrophic outcomes, including significant property losses and severe threats to public safety. Conventional traffic monitoring systems are limited in terms of accuracy and speed, presenting significant challenges for real-time traffic surveillance. To tackle these challenges, this paper introduces the GC-YOLOv9 algorithm. Specifically, we have enhanced the YOLOv9 model by incorporating Ghost Convolution, markedly improving the model’s perceptual abilities and detection accuracy. Furthermore, this study designed an integrated smart city framework that includes layers for service applications, the Internet of Things, edge processing, and data centers. By deploying the enhanced YOLOv9 model within this framework, our method achieved mAP@0.5 scores of 77.15 and 74.95 on the BDD100K and Cityscapes datasets, respectively, surpassing existing technologies. Additionally, the potential applications of this method in public area fire safety management, forest fire monitoring, and intelligent security systems further underscore its significant value in improving the safety and efficiency of smart cities.

Abstract The precise cellular mechanisms underlying heightened proinflammatory cytokine production during coronavirus infection remain incompletely understood. Here we identify the envelope (E) protein in severe coronaviruses (SARS-CoV-2, SARS, or MERS) as a potent inducer of interleukin-1 release, intensifying lung inflammation through the activation of TMED10-mediated unconventional protein secretion (UcPS). In contrast, the E protein of mild coronaviruses (229E, HKU1, or OC43) demonstrates a less pronounced effect. The E protein of severe coronaviruses contains an SS/DS motif, which is not present in milder strains and facilitates interaction with TMED10. This interaction enhances TMED10-oligomerization, facilitating UcPS cargo translocation into the ER-Golgi intermediate compartment (ERGIC)—a pivotal step in interleukin-1 UcPS. Progesterone analogues were identified as compounds inhibiting E-enhanced release of proinflammatory factors and lung inflammation in a Mouse Hepatitis Virus (MHV) infection model. These findings elucidate a molecular mechanism driving coronavirus-induced hyperinflammation, proposing the E-TMED10 interaction as a potential therapeutic target to counteract the adverse effects of coronavirus-induced inflammation.

Abstract Purpose To evaluate 18F-FDG myocardial metabolism imaging (MMI) using a total-body PET/CT scanner and explore the feasible scan duration to guide the clinical practice. Methods A retrospective analysis was conducted on 41 patients who underwent myocardial perfusion-metabolism imaging to assess myocardial viability. The patients underwent 18F-FDG MMI with a total-body PET/CT scanner using a list-mode for 600 s. PET data were trimmed and reconstructed to simulate images of 600-s, 300-s, 120-s, 60-s, and 30-s acquisition time (G600-G30). Images among different groups were subjectively evaluated using a 5-point Likert scale. Semi-quantitative evaluation was performed using standardized uptake value (SUV), myocardial to background activity ratio (M/B), signal to noise ratio (SNR), contrast to noise ratio (CNR), contrast ratio (CR), and coefficient of variation (CV). Myocardial viability analysis included indexes of Mismatch and Scar. G600 served as the reference. Results Subjective visual evaluation indicated a decline in the scores of image quality with shortening scan duration. All the G600, G300, and G120 images were clinically acceptable (score ≥ 3), and their image quality scores were 4.9 ± 0.3, 4.8 ± 0.4, and 4.5 ± 0.8, respectively (P > 0.05). Moreover, as the scan duration reduced, the semi-quantitative parameters M/B, SNR, CNR, and CR decreased, while SUV and CV increased, and significant difference was observed in G300-G30 groups when comparing to G600 group (P

Abstract Background In research to improve the quality of transgenic crops, it is often necessary to introduce multiple functionally related genes into recipient plants simultaneously to improve crop genetic traits effectively. Compared with unidirectional promoters, bidirectional promoters simultaneously regulate the expression of multiple genes and improve the efficiency of biotechnology. Therefore, in this study, bidirectional gene pairs were systematically analyzed in Gossypium hirsutum TM-1, and the structure, function and evolutionary relationships of the bidirectional genes were analyzed. The endogenous bidirectional promoters of cotton were mined, and their specific regulatory elements and biological functions were explored to provide useful promoter resources and a theoretical basis for cultivating new cotton germplasms with excellent fiber quality. Results Using an improved search model, a total of 1,383 bidirectional transcript pairs were identified in the Gossypium hirsutum TM-1 genome, and their gene structure and functional annotations were systematically analyzed. Thirty bidirectional intergenic sequences were randomly screened for promoter activity analysis via a transient expression system, and 25 intergenic sequences were found to have bidirectional promoter activity. Comparative analysis of the bidirectional gene profiles of the four cotton subspecies revealed that these subspecies presented abundant bidirectional gene pairs with high homology and that the bidirectional genes in the cotton subspecies were more similar in terms of their molecular functions, cellular components and biological processes. In addition, parallel analysis of bidirectional genes in dicotyledons and monocotyledons revealed that abundant bidirectional gene pairs exist in different species. Although the total number of orthologous bidirectional genes was similar, there was a significant difference in the number of orthologous bidirectional gene pairs between dicotyledons and monocotyledons. This evolutionary analysis of the function and structure of homologous bidirectional gene pairs in different varieties and different subspecies of the same species revealed potential pathways by which these gene pairs originated, which may be necessary for the evolution of a new species. Conclusion In this study, many bidirectional gene pairs in Gossypium hirsutum TM-1 were identified using computer programming, and systematic analysis was conducted to explore their functions and evolutionary relationships. In addition, the promoter activity of the bidirectional intergenic sequences was verified. The combination of computer programming screening, experimental validation and other methods is expected to provide preferred bidirectional promoters for transgenic breeding work via multigene cotransformation methods, and this information is valuable for genetic engineering research and applications.

Abstract Sorghum ratooning, a time and labor-saving cultivation practice, is increasingly being adopted by farmers in Southwest China as an alternative. Efficient N fertilizer management is critical for economical production of sorghum and the long-term protection of the environment. To investigate the impact of N management on grain yield and nitrogen use efficiencies (NUEs) of ratoon sorghum system, a three-year field experiment was conducted for Jinyunuo3 (a hybrid cultivar) and Guojiaohong1 (an inbred cultivar) using 12 combinations of N rates and splitting ratios. The results showed that increasing N rate and splitting application times led to improvements in various growth parameters such as dry matter weight, crop growth rate (CGR), leaf area index (LAI), and photosynthetic potential (PP). The main, ratoon, and annual yields increased with N rate increase, but there was no significant difference between 225 and 150 kg N ha−1 in the ratoon and annual yields. Splitting the application of N fertilizer enhanced grain yield compared to a single dose application method, especially three-split applications yielded higher than two-split applications. Compared with N rates of 225 and 150 kg ha−1, N rate of 75 kg ha−1 increased apparent recovery rate of applied nitrogen (REN), agronomic efficiency of applied nitrogen (AEN), and partial factor productivity from applied nitrogen (PFPN) in both main season and whole year. But through splitting application methods at high N rates could achieve similar or even higher levels of NUEs compared to all applied as basal fertilizer at low N rates. Therefore, it could be recommended that applying 150 kg N ha−1 with a basal-jointing-heading fertilizer ratio of 2:4:4 represented an efficient N management practice to synchronously obtain high grain yield and NUEs in ratoon sorghum system in Southwest China.

Abstract Background Previous research has revealed the potential impact of circadian rhythms on pulmonary diseases; however, the connection between circadian rhythm-associated Thyrotroph Embryonic Factor (TEF) and Pulmonary Arterial Hypertension (PAH) remains unclear. We aim to assess the genetic causal relationship between TEF and PAH by utilizing two sets of genetic instrumental variables (IV) and publicly available Pulmonary Arterial Hypertension Genome-Wide Association Studies (GWAS). Methods Total of 23 independent TEF genetic IVs from recent MR reports and PAH GWAS including 162,962 European individuals were used to perform this two-sample MR study. Gain- and loss-of-function experiments were used to demonstrate the role of TEF in PAH. Results Our analysis revealed that as TEF levels increased genetically, there was a corresponding increase in the risk of PAH, as evidenced by IVW (OR = 1.233, 95% CI: 1.054–1.441; P = 0.00871) and weighted median (OR = 1.292, 95% CI for OR: 1.064–1.568; P = 0.00964) methods. Additionally, the up-regulation of TEF expression was associated with a significantly higher likelihood of abnormal circadian rhythm (IVW: P = 0.0024733, β = 0.05239). However, we did not observe a significant positive correlation between circadian rhythm and PAH (IVW: P = 0.3454942, β = 1.4980398). In addition, our in vitro experiments demonstrated that TEF is significantly overexpressed in pulmonary artery smooth muscle cells (PASMCs). And overexpression of TEF promotes PASMC viability and migratory capacity, as well as upregulates the levels of inflammatory cytokines. Conclusion Our analysis suggests a causal relationship between genetically increased TEF levels and an elevated risk of both PAH and abnormal circadian rhythm. Consequently, higher TEF levels may represent a risk factor for individuals with PAH.

A novel underwater in-situ wire-based laser additive manufacturing (ULAM) technology is proposed for the in-service repair of underwater components in nuclear power plant. Duplex stainless steel (DSS) obtained in air and underwater environments were analysed using material characterisation and testing methods. The effects of underwater additive environments on the microstructure evolution, mechanical properties and corrosion resistance of the specimens were investigated. The results show that the laser heat input is consumed to balance the heat loss of the water-cooled base material during the underwater laser additive manufacturing process, leading to a reduction in the heat input to the molten pool. Underwater specimen exhibit a two-phase balance, with small ferrite grain boundary angles, resulting in better tensile strength and corrosion resistance. Laser reheat treatment leads to a phase change in microstructure, which can enhance the microhardness and the tensile strength. The ULAM system can meet the requirements of actual engineering for cladding layer.

The activating transcription factor (ATF)/ cAMP-response element binding protein (CREB) family represents a large group of basic zone leucine zip (bZIP) transcription factors (TFs) with a variety of physiological functions, such as endoplasmic reticulum (ER) stress, amino acid stress, heat stress, oxidative stress, integrated stress response (ISR) and thus inducing cell survival or apoptosis. Interestingly, ATF family has been increasingly implicated in autophagy and ferroptosis in recent years. Thus, the ATF family is important for homeostasis and its dysregulation may promote disease progression including cancer. Current therapeutic approaches to modulate the ATF family include direct modulators, upstream modulators, post-translational modifications (PTMs) modulators. This review summarizes the structural domain and the PTMs feature of the ATF/CREB family and comprehensively explores the molecular regulatory mechanisms. On this basis, their pathways affecting proliferation, metastasis, and drug resistance in various types of cancer cells are sorted out and discussed. We then systematically summarize the status of the therapeutic applications of existing ATF family modulators and finally look forward to the future prospect of clinical applications in the treatment of tumors by modulating the ATF family.

IntroductionAthletes’ capability to perform activities with body rotation could be weakened by fatigue accumulation. Making pivot turning in unanticipated scenarios after fatigue may greatly challenge athletes’ ability to adapt rational motion strategies, elevating the risk of anterior cruciate ligament (ACL) injury. This study aimed to investigate the effects of fatigue and anticipation on biomechanical risk factors of ACL injury during 180° pivot turns in female soccer players.MethodsTwenty-one female soccer players were selected as participants. The participants performed anticipated turning maneuver before the fatigue intervention. The participants sprinted along the runway, decelerated and planted their foot on the force plate, and then executed a 180° pivot turn. For unanticipated tests, the pivot turn was mixed with side/cross-cuts, which were indicated to the participant using a custom-designed light system. The tests were repeated by the participant after receiving a fatigue intervention. Lower-limb joint angles and moments were characterized. Peak ground reaction forces (GRFs) and GRF loading rates were determined. Two-way repeated measures analysis of variance was applied to examine the effects of fatigue and anticipation on the variables of interest.ResultsCompared to the anticipated conditions, the approach speed was significantly lower in the unanticipated tests (P < 0.0001). Lower-limb kinematics showed varied angular patterns across conditions: greater hip joint variations in flexion, abduction, and internal rotation during unanticipated turns; consistent knee joint flexion and ankle plantarflexion with dorsiflexion observed mid-turn. Significant interactions (P = 0.023 to P = 0.035) between fatigue and anticipation influenced hip joint angles. Anticipation effects were notable at initial contact and peak ground reaction force, increasing hip, knee, and ankle joint angles (P < 0.0001 to P = 0.012). Participants showed consistent ground reaction force (GRF) patterns during pivot turns across fatigue and anticipation conditions, with the first peak occurring approximately 10% into the turn period. Significant interaction effects (P = 0.016) between fatigue and anticipation were observed for knee flex/extension moments at the first peak vertical GRF. Anticipation significantly increased first peak vertical (P < 0.0001), anteroposterior (P < 0.0001), and mediolateral (P < 0.0001) GRFs. Fatigue increased first peak vertical (P = 0.022), anteroposterior (P = 0.018), and mediolateral (P = 0.019) GRFs. Post-fatigue, participants exhibited reduced first peak GRFs and loading rates compared to pre-fatigue conditions, with higher rates observed in unanticipated turns (vertical GRF: P = 0.030; anteroposterior GRF: P < 0.0001).ConclusionFemale soccer players’ lower-limb Biomechanical characterization could be greatly affected by the change of anticipatory scenarios. With the associated increase of GRF, the risk of their ACL injury might be elevated. Fatigue affected female soccer players’ abilities on movement performances, but the interaction of these two factors could potentially weaken their knee’s functions during pivot turns. Cognitive training on unanticipated tasks may be important for rehabilitation training after ACL injury.

BackgroundProlonged postoperative hospital stay following gastric cancer (GC) surgery is an important risk factor affecting patients’ mood and increasing complications. We aimed to develop a nomogram to predict risk factors associated with prolonged postoperative length of stay (PLOS) in patients undergoing gastric cancer resection.MethodsData were collected from 404 patients. The least absolute shrinkage and selection operator (LASSO) was used for variable screening, and a nomogram was designed. The nomogram performance was evaluated by the area under the receiver operating characteristic curve (AUC). The consistency between the predicted and actual values was evaluated via a calibration map, and the clinical application value was evaluated via decision curve analysis (DCA) and clinical impact curve analysis (CICA).ResultsA total of 404 patients were included in this study. Among these patients, 287 were assigned to the training cohort, and 117 were assigned to the validation cohort. According to the PLOS quartile distance, 103 patients were defined as having prolonged PLOS. LASSO regression and logistic multivariate analysis revealed that 4 clinical characteristics, the neutrophil–lymphocyte ratio (NLR) on postoperative day one, the NLR on postoperative day three, the preoperative prognostic nutrition index and the first time anal exhaust was performed, were associated with the PLOS and were included in the construction of the nomogram. The AUC of the nomogram prediction model was 0.990 for the training set and 0.983 for the validation set. The calibration curve indicated good correlation between the predicted results and the actual results. The Hosmer-Lemeshow test revealed that the P values for the training and validation sets were 0.444 and 0.607, respectively, indicating that the model had good goodness of fit. The decision curve analysis and clinical impact curve of this model showed good clinical practicability for both cohorts.ConclusionWe explored the risk factors for prolonged PLOS in GC patients via the enhanced recovery after surgery (ERAS) program and developed a predictive model. The designed nomogram is expected to be an accurate and personalized tool for predicting the risk and prognosis of PLOS in GC patients via ERAS measures.

Abstract Cardiac fibroblasts (CFs) are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure (HF). TEAD1 has been shown to be essential for heart development and homeostasis. However, fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely understood. Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction (TAC) and Ang-II infusion. Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload. Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs- and myofibroblasts-specific Cre mice. Echocardiographic and histological analyses demonstrated that CFs- and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor, VT103, ameliorated TAC-induced cardiac remodeling. Mechanistically, RNA-seq and ChIP-seq analysis identified Wnt4 as a novel TEAD1 target. TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway, and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression. Furthermore, co-immunoprecipitation combined with mass spectrometry, chromatin immunoprecipitation, and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4, leading to the binding and activation of the Wnt4 promoter. In conclusion, TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signalling pathway.

Abstract Background The risk and timing of permanent pacemaker implantation (PPMI) after transcatheter aortic valve replacement (TAVR) is still hard to predict. We aimed to analyze the relationship between the compression ratio of a self-expandable valve (SEV) and the need for PPMI after TAVR. Methods A total of 106 patients who were implanted with the VitaFlow transcatheter aortic valve system and for whom complete imaging information was available were included in this retrospective cohort study. Eight lines perpendicular to the long axis of the SEV were drawn (the top and bottom of the SEV and the intersection of each row of wires) for measurement purposes. The compression ratio was calculated as 1 − (in vivo meridian/in vitro meridian) and compared between patients undergoing and those not undergoing PPMI after adjusting for implantation depth. Multivariable logistic regression and Cox proportional hazards models were used to assess factors associated with the risk and timing of the need for PPMI. Results Fifteen (14.2%) patients underwent PPMI after TAVR. Patients with a higher mean compression ratio (20%, odds ratio [OR] = 214.82; p

Accurate prediction of the structurally diverse complementarity determining region heavy chain 3 (CDR-H3) loop structure remains a primary and long-standing challenge for antibody modeling. Here, we present the H3-OPT toolkit for predicting the 3D structures of monoclonal antibodies and nanobodies. H3-OPT combines the strengths of AlphaFold2 with a pre-trained protein language model and provides a 2.24 Å average RMSDCα between predicted and experimentally determined CDR-H3 loops, thus outperforming other current computational methods in our non-redundant high-quality dataset. The model was validated by experimentally solving three structures of anti-VEGF nanobodies predicted by H3-OPT. We examined the potential applications of H3-OPT through analyzing antibody surface properties and antibody–antigen interactions. This structural prediction tool can be used to optimize antibody–antigen binding and engineer therapeutic antibodies with biophysical properties for specialized drug administration route.

Background: Patent foramen ovale (PFO) is associated with migraine; however, the mechanism of PFO-associated migraine is not well known; additionally, percutaneous closure is controversial. This study aimed to investigate in situ thrombi within the PFO and explore the possible predictors of the effectiveness of PFO closure in migraineurs. Methods: This prospective cohort study included 48 asymptomatic patients and 92 migraineurs with PFO. Optical coherence tomography (OCT) was used to evaluate the PFO microstructure. Only migraineurs underwent percutaneous closure. Migraineurs were divided into two cohorts based on the presence of a thrombus within the PFO. The symptoms were assessed at the 12-month follow-up visit. Predictors were evaluated employing multivariate logistic regression and receiver operating characteristic curve analyses. Results: In situ thrombi within PFO were identified in 69 migraineurs and in two asymptomatic patients (76.7 % vs. 4.3 %; P

Delayed luminescence (DL) refers to the photon-induced ultra-weak luminescence emitted by samples after the light source is switched off. As a noninvasive method for health monitoring and disease diagnosis, DL has attracted increasing attention. The further development of this technology is valuable for the study of complex biological processes, such as different growth stages. If such studies were to be conducted in humans, large numbers of subjects of all ages would need to be recruited, and individual differences would be inevitable. The budding yeast Saccharomyces cerevisiae (S. cerevisiae) has a short population lifespan, and the growth phases can be monitored within dozens of hours. Therefore, S. cerevisiae is an ideal model organism for research. In this study, we investigated the physiological characteristics and DL emission of S. cerevisiae during growth in glucose-based media and entry into stationary phase, and the results showed that DL kinetic curves of yeast cells in the growing phase were obviously separated from those of stationary phase cells. Moreover, the metabolic and physiological characteristics of the yeast cell population were discussed using the DL emission parameters I0, τ and γ. We also discussed the possibility of assessing entropy using DL emission parameters. Our research demonstrates the potential of this technology to be used in wider applications.

Soybean, a primary vegetable protein source, boasts favorable amino acid profiles; however, its composition still falls short of meeting human nutritional demands. The soybean amino acid content is a quantitative trait controlled by multiple genes. In this study, an F2 population of 186 individual plants derived from the cross between ChangJiangChun2 and JiYu166 served as the mapping population. Based on the previously published genetic map of our lab, we increased the density of the genetic map and constructed a new genetic map containing 518 SSR (simple sequence repeats) markers and 64 InDel (insertion-deletion) markers, with an average distance of 5.27 cm and a total length of 2881.2 cm. The content of eight essential amino acids was evaluated in the F2:5, F2:6, and BLUP (best linear unbiased prediction). A total of 52 QTLs (quantitative trait loci) were identified, and 13 QTL clusters were identified, among which loci02.1 and loci11.1 emerged as stable QTL clusters, exploring candidate genes within these regions. Through GO enrichment and gene annotation, 16 candidate genes associated with soybean essential amino acid content were predicted. This study would lay the foundation for elucidating the regulatory mechanisms of essential amino acid content and contribute to germplasm innovation in soybeans.

The demand for freshwater is increasing with population growth and rapid socio-economic development. It is more and more important for refined irrigation water management to conduct research on crop evapotranspiration (ET) data with a high spatiotemporal resolution in agricultural regions. We propose the unmixing–weight ET image fusion model (UWET), which integrates the advantages of the unmixing method in spatial downscaling and the weight-based method in temporal prediction to produce daily ET maps with a high spatial resolution. The Landsat-ET and MODIS-ET datasets for the UWET fusion data are retrieved from Landsat and MODIS images based on the surface energy balance model. The UWET model considers the effects of crop phenology, precipitation, and land cover in the process of the ET image fusion. The precision evaluation is conducted on the UWET results, and the measured ET values are monitored by eddy covariance at the Luancheng station, with average MAE values of 0.57 mm/day. The image results of UWET show fine spatial details and capture the dynamic ET changes. The seasonal ET values of winter wheat from the ET map mainly range from 350 to 660 mm in 2019–2020 and from 300 to 620 mm in 2020–2021. The average seasonal ET in 2019–2020 is 499.89 mm, and in 2020–2021, it is 459.44 mm. The performance of UWET is compared with two other fusion models: the Spatial and Temporal Adaptive Reflectance Fusion Model (STARFM) and the Spatial and Temporal Reflectance Unmixing Model (STRUM). UWET performs better in the spatial details than the STARFM and is better in the temporal characteristics than the STRUM. The results indicate that UWET is suitable for generating ET products with a high spatial–temporal resolution in agricultural regions.

Abstract Radiomics is widely used in adult tumors but has been rarely applied to the field of pediatrics. Promoting the application of radiomics in pediatric diseases, especially in the early diagnosis and stratified treatment of tumors, is of great value to the realization of the WHO 2030 “Global Initiative for Childhood Cancer.” This paper discusses the general characteristics of radiomics, the particularity of its application to pediatric diseases, and the current status and prospects of pediatric radiomics. Radiomics is a data‐driven science, and the combination of medicine and engineering plays a decisive role in improving data quality, data diversity, and sample size. Compared with adult radiomics, pediatric radiomics is significantly different in data type, disease spectrum, disease staging, and progression. Some progress has been made in the identification, classification, stratification, survival prediction, and prognosis of tumor diseases. In the future, big data applications from multiple centers and cross‐talent training should be strengthened to improve the benefits for clinical workers and children.

Background: Data regarding the prognosis of Eisenmenger syndrome (ES) and effect of targeted drugs are limited. This study aimed to analyze the prognosis and impact of targeted drug therapy on the survival rate of patients with ES in the Chinese population. Methods: The data of patients with ES referred to our hospital between January 2010 and December 2020 were retrospectively analyzed. Data included baseline demographics, echocardiographic parameters, and clinical diagnoses. All patients were followed up via telephone interviews in February 2022. The primary endpoint was mortality. Results: Overall, 1,021 patients with ES were included. The 1-, 3-, 5-, 7-, 10-, and 12-year survival rates were 91.6%, 84.2%, 80.7%, 73.8%, 71.4%, and 69.9%, respectively. Patients with atrial septal defects had the best prognosis than those with ventricular septal defects, patent ductus arteriosus, and complex congenital heart disease (CHD) (P

Abstract Background This study aims to develop a post-procedural risk prediction model for permanent pacemaker implantation (PPMI) in patients treated with transcatheter aortic valve replacement (TAVR). Methods 336 patients undergoing TAVR at a single institution were included for model derivation. For primary analysis, multivariate logistic regression model was used to evaluate predictors and a risk score system was devised based on the prediction model. For secondary analysis, a Cox proportion hazard model was performed to assess characteristics associated with the time from TAVR to PPMI. The model was validated internally via bootstrap and externally using an independent cohort. Results 48 (14.3%) patients in the derivation set had PPMI after TAVR. Prior right bundle branch block (RBBB, OR: 10.46; p

Abstract Although the ‘one ticket transfer’ mode brings convenience to passengers, it also poses challenges to the passenger flow assignment. The current widely used multi‐path probability assignment model based on traffic cost realizes the passenger flow distribution from the macro‐perspective but lacks the consideration of passenger attributes and the time‐varying characteristics of passenger travel time. Here, a novel spatiotemporal path inference model is proposed for Urban Rail Transit (URT) passengers based on the travel time data and train operation information. In this study, the impact of passengers detained at the platform on passenger travel itinerary is considered by characterizing the passenger detention rate. The proposed method realizes the reverse inference of passenger path from the micro‐perspective, and can accurately describe the specific travel process of each passenger. Moreover, the real‐world data of Shenzhen Metro in China is taken to verify the rationality of the proposed model. The results show that the model is in good agreement with the existing clearance model and can accurately infer the passenger travel itinerary from the micro‐perspective. The proposed method provides a more refined solution for the spatial‐temporal assignment of URT passenger flow.

Abstract Background This study aimed to retrospectively evaluate the feasibility of total-body 18F-FDG PET/CT ultrafast acquisition combined with a deep learning (DL) image filter in the diagnosis of colorectal cancers (CRCs). Methods The clinical and preoperative imaging data of patients with CRCs were collected. All patients underwent a 300-s list-mode total-body 18F-FDG PET/CT scan. The dataset was divided into groups with acquisition durations of 10, 20, 30, 60, and 120 s. PET images were reconstructed using ordered subset expectation maximisation, and post-processing filters, including a Gaussian smoothing filter with 3 mm full width at half maximum (3 mm FWHM) and a DL image filter. The effects of the Gaussian and DL image filters on image quality, detection rate, and uptake value of primary and liver metastases of CRCs at different acquisition durations were compared using a 5-point Likert scale and semi-quantitative analysis, with the 300-s image with a Gaussian filter as the standard. Results All 34 recruited patients with CRCs had single colorectal lesions, and the diagnosis was verified pathologically. Of the total patients, 11 had liver metastases, and 113 liver metastases were detected. The 10-s dataset could not be evaluated due to high noise, regardless of whether it was filtered by Gaussian or DL image filters. The signal-to-noise ratio (SNR) of the liver and mediastinal blood pool in the images acquired for 10, 20, 30, and 60 s with a Gaussian filter was lower than that of the 300-s images (P 0.05). Conclusions The DL filter can significantly improve the image quality of total-body 18F-FDG PET/CT ultrafast acquisition. Deep learning-based image filtering methods can significantly reduce the noise of ultrafast acquisition, making them suitable for clinical diagnosis possible.

BackgroundFollowing the COVID-19 pandemic, another large-scale respiratory epidemic has emerged in China, causing significant social impact and disruption. The article is to explore the patients’ psychological and behavioral responses to the enhancement of healthcare quality.MethodsBased on the five dimensions of the Self-Regulation Common-Sense Model, we developed an interview outline to explore the process by which patients identify disease symptoms to guide action plans and coping strategies. The researchers used a semi-structured interview format to simultaneously collect data online and offline. This study gathered data from 12 patients with mixed respiratory infections, comprising 58% females and 42% males; the average age was 30.67 years (SD 20.00), with 91.7% infected with two pathogens and 8.3% with three. The data analysis employed the KJ method, themes were inductively analyzed and categorized from semi-structured interview results, which were then organized into a coherent visual and logical pathway.Key resultsThe study identified 5 themes: (1) Autonomous Actions Prior to Seeking Medical Care; (2) Decision-Making in Seeking Hospital Care; (3) Disease Shock; (4) Public Crisis Response; (5) Information Cocoon.ConclusionThe pandemic of respiratory infectious diseases has not ceased in recent years. Following the COVID-19 pandemic, China is now facing a trend of concurrent epidemics involving multiple respiratory pathogens. This study centers on patients’ health behaviors, exploring the potential relationships among various factors that affect these behaviors. The aim is to provide references and grounds for the improvement of healthcare services when such public health events reoccur.

Objective: To evaluate the effects of Fuzheng Qingdu Decoction (FZQDD) on the autonomic function and cancer-related symptoms of patients with advanced gastric cancer undergoing chemotherapy to verify its clinical efficacy. Methods: Sixty-two patients with stage III or IV gastric cancer were included in this study. The patients were divided into 2 groups: the chemotherapy (33 patients) and chemotherapy with FZQDD (29 patients) groups. The primary outcome was the autonomic function of the patients before and after the interventions. The parameters that were used to assess autonomic function were deceleration capacity (DC) and acceleration capacity (AC) of heart rate and heart rate variability (HRV), which comprised standard deviation of the normal-normal interval (SDNN), root mean square of successive interval differences (RMSSD), low-frequency power (LF), high-frequency power (HF), total power (TP), and LF–HF ratio. The secondary outcomes were cancer-related symptoms and the quality of life. Results: DC and HRV parameters (ie, SDNN, RMSSD, LF, HF, and TP) were significantly decreased in the chemotherapy group; however, AC significantly increased after the interventions. No significant differences were observed in the DC, AC, and HRV parameters before and after the interventions in the chemotherapy with FZQDD group. Nevertheless, the changes in DC, AC, and HRV parameters (SDNN, RMSSD, HF, and TP) before and after the interventions were statistically significant between both the groups. FZQDD significantly improved the cancer-related symptoms and the quality of life of the patients. Conclusions: Oxaliplatin combined with S-1 (tegafur, gimeracil, and oteracil potassium) can impair autonomic modulation in patients with advanced gastric cancer. FZQDD can alleviate autonomic dysfunction by increasing the parasympathetic activity and decreasing the sympathetic tone, helping patients restore the dynamic sympathovagal balance, and significantly improving the cancer-related symptoms and the quality of life of patients.

Objective. This study aimed to investigate the application value of intracardiac echocardiography (ICE) in transcatheter closure of a patent foramen ovale (PFO) combined with an adjacent atrial septal defect (ASD). Methods. This retrospective study included five patients with PFO combined with adjacent ASD who underwent transcatheter closure and were admitted to the Zhongshan Hospital of Fudan University from June to September 2023. General conditions, ultrasound and ICE findings, and operative data were recorded and followed up for 2–6 months. Results. Of the five patients, two and three had embolic stroke of undetermined source and migraine, respectively, aged 45.6 ± 12.0 years. All patients underwent successful transcatheter closure via the PFO tunnel under the guidance of ICE, without complications or new stroke, and showed significantly reduced migraine at the follow-up. Conclusion. In patients with PFO combined with adjacent ASD, closure of a PFO tunnel could be successfully achieved under ICE guidance; its clinical efficacy was accurate and worthy of promotion.

Insufficient data exist regarding the investigation of the impact of novel oral anticoagulants (NOACs) on coagulation activation biomarkers in the context of left atrial appendage closure (LAAC) and device-related thrombosis (DRT). The study was designed to investigate the changes and presence of coagulation activation biomarkers between different antithrombotic strategies following LAAC. A total of 120 nonvalvular atrial fibrillation patients intolerant of long-term anticoagulants, who underwent successful WATCHMAN closure implantation, were enrolled (rivaroxaban, n=82; dabigatran, n=38). Blood samples were obtained from left atrium (LA) and left atrial appendage (LAA) during the operation and fasting blood samples on the same day of LAAC and 45 days after discharge. The biochemical indicators, thrombin-antithrombin complex (TAT), soluble P-selectin (sP-selectin), von Willebrand factor (vWF), and CD40 ligand (CD40L), were measured by enzyme-linked immunosorbent assay. The primary endpoints of this study were the efficacy and safety characteristics of different antithrombotic strategies, including DRT incidence, stroke or transient ischemic attack, systemic embolism, and clinical major and nonmajor bleeding complications during the follow-up of 180 days. The results revealed that TAT, vWF, sP-selectin, and CD40L levels in vein were significantly reduced by 2.4% (p=0.043), 5.0% (p

Abstract YES proto‐oncogene 1 (YES1) is an SRC family kinase (SFK) that plays a key role in cancer cell proliferation, adhesion, invasion, survival, and angiogenesis during tumorigenesis and tumor development. Reports suggest that YES1 amplification is associated with resistance to chemotherapeutic drugs and tyrosine kinase inhibitors (TKIs) in human malignancies. However, the mechanisms of drug resistance have not been fully elucidated. In this article, we review the literature on YES1 and discuss the implications of YES1 signaling for targeted therapy and chemotherapy resistance in malignancies. Moreover, recent advances in targeted therapy for YES1‐amplified malignancies are summarized. Finally, we conclude that targeting YES1 may reverse drug resistance and serve as a valuable tumor treatment strategy.

Abstract Background Invasion of the corpus callosum by sparganosis is rare in children. After invading the corpus callosum, sparganosis has various migration modes, which can break through the ependyma and enter the ventricles, thus causing secondary migratory brain injury. Case presentation A girl aged 4 years and 7 months presented with left lower limb paralysis for more than 50 days. Blood examination showed that the proportion and absolute number of eosinophils in the peripheral blood were increased. Furthermore, enzyme-linked immunosorbent assay of serum and cerebrospinal fluid samples revealed positivity for IgG and IgM antibodies for sparganosis. Initial magnetic resonance imaging (MRI) revealed ring-like enhancements in the right frontoparietal cortex, subcortical white matter, and splenium of the corpus callosum. Within 2 months, a fourth follow-up MRI showed that the lesion had spread to the left parietal cortex, subcortical white matter, and deep white matter in the right occipital lobe and right ventricular choroid plexus, with left parietal leptomeningeal enhancement. Conclusion Migratory movement is one of the characteristics of cerebral sparganosis. When sparganosis invades the corpus callosum, clinicians should be aware that it may then break through the ependyma and enter the lateral ventricles, leading to secondary migratory brain injury. Short-term follow-up MRI is necessary to evaluate the migration mode of sparganosis and dynamically guide treatment strategies.

Background: Prior research suggests that autonomic modulation investigated by heart rate variability (HRV) might act as a novel predictive biomarker for cancer prognosis, such as in breast cancer and pancreatic cancer. It is not clear whether there is a correlation between autonomic modulation and prognosis in patients with extensive-stage small cell lung cancer (ES-SCLC). Therefore, the purpose of the study was to examine the association between short-term HRV, deceleration capacity (DC) and acceleration capacity (AC) of heart rate and overall survival in patients with ES-SCLC.Methods: We recruited 40 patients with ES-SCLC, and 39 were included in the final analysis. A 5-min resting electrocardiogram of patients with ES-SCLC was collected using a microelectrocardiogram recorder to analyse short-term HRV, DC and AC. The following HRV parameters were used: standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD). Overall survival of patients with ES-SCLC was defined as time from the date of electrocardiogram measurement to the date of death or the last follow-up. Follow-up was last performed on 07 June 2023. There was a median follow-up time of 42.2 months.Results: Univariate analysis revealed that the HRV parameter SDNN, as well as DC significantly predicted the overall survival of ES-SCLC patients (all p < 0.05). Multivariate analysis showed that the HRV parameters SDNN (hazard ratio = 5.254, 95% CI: 1.817–15.189, p = 0.002), RMSSD (hazard ratio = 3.024, 95% CI: 1.093–8.372, p = 0.033), as well as DC (hazard ratio = 3.909, 95% CI: 1.353–11.293, p = 0.012) were independent prognostic factors in ES-SCLC patients.Conclusion: Decreased HRV parameters (SDNN, RMSSD) and DC are independently associated with shorter overall survival in ES-SCLC patients. Autonomic nervous system function (assessed based on HRV and DC) may be a new biomarker for evaluating the prognosis of patients with ES-SCLC.

IntroductionLymphovascular space invasion (LVSI) is associated with lymph node metastasis and poor prognosis in cervical cancer. In this study, we investigated the potential of radiomics, derived from magnetic resonance (MR) images using habitat analysis, as a non-invasive surrogate biomarker for predicting LVSI in cervical cancer.MethodsThis retrospective study included 300 patients with cervical cancer who underwent surgical treatment at two centres (centre 1 = 198 and centre 2 = 102). Using the k-means clustering method, contrast-enhanced T1-weighted imaging (CE-T1WI) images were segmented based on voxel and entropy values, creating sub-regions within the volume ofinterest. Radiomics features were extracted from these sub-regions. Pearson correlation coefficient and least absolute shrinkage and selection operator LASSO) regression methods were used to select features associated with LVSI in cervical cancer. Support vector machine (SVM) model was developed based on the radiomics features extracted from each sub-region in the training cohort.ResultsThe voxels and entropy values of the CE-T1WI images were clustered into three sub-regions. In the training cohort, the AUCs of the SVM models based on radiomics features derived from the whole tumour, habitat 1, habitat 2, and habitat 3 models were 0.805 (95% confidence interval [CI]: 0.745–0.864), 0.873(95% CI: 0.824–0.922), 0.869 (95% CI: 0.821–0.917), and 0.870 (95% CI: 0.821–0.920), respectively. Compared with whole tumour model, the predictive performances of habitat 3 model was the highest in the external test cohort (0.780 [95% CI: 0.692–0.869]).ConclusionsThe radiomics model based on the tumour sub-regional habitat demonstrated superior predictive performance for an LVSI in cervical cancer than that of radiomics model derived from the whole tumour.

Developing ultrahigh-strength structural materials that are ductile, fracture resistant, and cost effective has been a long-standing desire for scientists and engineers. Surface nano-crystallization technology has recently been developed as one of the most effective methods to optimize surface structure, which can improve local and global mechanical behavior without compromising ductility. This technique involves the use of hundreds of small hard balls vibrated by high-power ultrasound so that they impact onto the surface of a material at high speed, also known as surface mechanical abrasion treatment (SMAT). Despite its success in enhancing the mechanical properties of steels and other structural materials, there is still lack of clear understanding of the relationships between desired surface structures/properties and controlling parameters in such surface treatment processes. Therefore, we calculated residual stress through computational modeling such as finite element analysis (FEA), and simulated the effect of all parameters during processing on residual compressive stress. Different multiple impact models are investigated to develop a more realistic model for the strengthening process.

There is increasing interest in machine assistance for literary translation, but research on how computer-assisted translation (CAT) tools and machine translation (MT) combine in the translation of literature is still incipient, especially for non-European languages. This article presents two exploratory studies where English-to-Chinese translators used neural MT to translate science fiction short stories in Trados Studio. One of the studies compares post-editing with a ‘no MT’ condition. The other examines two ways of presenting the texts on screen for postediting, namely by segmenting them into paragraphs or into sentences. We collected the data with the Qualititivity plugin for Trados Studio and describe a method for analysing data collected with this plugin through the translation process research database of the Center for Research in Translation and Translation Technology (CRITT). While post-editing required less technical effort, we did not find MT to be appreciably timesaving. Paragraph segmentation was associated with less postediting effort on average, though with high translator variability. We discuss the results in the light of broader concepts, such as status-quo bias, and call for more research on the different ways in which MT may assist literary translation, including its use for comparison purposes or, as mentioned by a participant, for ‘inspiration’.

Enabling a flexible and natural human-robot interaction (HRI) for industrial robots is a critical yet challenging task that can be facilitated by the use of conversational artificial intelligence (AI). Prior research has concentrated on strengthening interactions through the deployment of social robots, while disregarding the capabilities required to boost the flexibility and user experience associated with human-robot collaboration (HRC) on manufacturing tasks. One of the main challenges is the lack of publicly available industrial-oriented dialogue datasets for the training of conversational AI. In this work, we present an Industrial Robot Wizard-of-Oz Dialoguing Dataset (IRWoZ) focused on enabling HRC in manufacturing tasks. The dataset covers four domains: assembly, transportation, position, and relocation. It is created using the Wizard-of-Oz technique to be less noisy. We manually constructed, annotated and validated dialogue segments (e.g., intentions, slots, annotations), as well as the responses. Building upon the proposed dataset, we benchmark it on the state-of-the-art (SoTA) language models, generative pre-trained (GPT-2) models, on dialogue state tracking and response generation tasks. We expect that the IRWoZ dataset will facilitate exciting ongoing dialogue research and we provide it freely accessible at https://github.com/lcroy/ToD4IR/tree/main/dataset.

Abstract Background There is a lack of available data on specific prognostic comparisons between transcatheter aortic valve replacement (TAVR) using self-expandable valves (SEV) in patients with stenotic Type 0, Type 1 bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). Objectives To evaluate the association between aortic valve morphology and outcomes following self-expandable TAVR. Methods Consecutive patients with aortic stenosis(AS) undergoing self-expandable TAVR were enrolled and categorized into three groups (Type 0/Type 1 BAV or TAV) according to the Sievers classification. The primary endpoint was a composite of all-cause mortality and rehospitalization for heart failure (HF) within 2 years. Secondary outcomes included procedural complications and major cardiovascular events observed in clinical follow-ups. Clinical outcomes at 2 years following TAVR were compared among three groups using Kaplan-Meier curve and multivariable Cox proportional hazards regression models. Results A total of 344 AS patients (Type 0: 86; Type 1: 109; TAV: 149) were enrolled. The presence of moderate or severe paravalvular leak (PVL) was significantly higher in patients with Type 0 and Type 1 BAV versus TAV (10.47% vs. 16.51% vs. 6.71%, p = 0.043). All-cause 30-day mortality (2.33% vs. 0.92% vs. 2.68%, p = 0.626) and 2-year mortality (3.49% vs. 5.50% vs. 6.71%, p = 0.657) was comparable among the three groups. However, rehospitalization for HF within 2 years was significantly higher in Type 1 BAV (11.63% vs. 20.18% vs. 8.72%, p = 0.020). Multivariate Cox analysis showed that a higher STS score, Type 1 BAV morphology and excess leaflet calcification (≥ median calcium volume (CV) of the entire population) were independent predictors for HF rehospitalization. Additional intragroup Kaplan‒Meier analysis showed that excess leaflet calcification could predict higher long-term mortality and rehospitalization risk for HF(HR (95% CI): 3.430 (1.166–10.090), log rank p = 0.017) in Type 1 BAV patients. Conclusion Outcomes of self-expandable TAVR in BAV-AS patients might vary depending on valve subtypes. BAV patients with excess leaflet calcification and a raphe, especially calcified, had an increased risk of moderate PVL and HF readmission in mid-to-long term follow-ups.

BackgroundPrior research suggests that cardiovascular autonomic dysfunction might be an early marker of cardiotoxicity induced by antitumor treatment and act as an early predictor of cardiovascular disease-related morbidity and mortality. The impact of thoracic radiotherapy on the parasympathetic and sympathetic nervous systems, however, remains unclear. Therefore, this study aimed to evaluate the short-term effects of thoracic radiotherapy on the autonomic nervous system, using deceleration capacity (DC), acceleration capacity (AC) of heart rate, and heart rate variability (HRV) as assessment tools.MethodsA 5 min electrocardiogram was collected from 58 thoracic cancer patients before and after thoracic radiotherapy for DC, AC, and HRV analysis. HRV parameters employed included the standard deviation of the normal-normal interval (SDNN), root mean square of successive interval differences (RMSSD), low frequency power (LF), high frequency power (HF), total power (TP), and the LF to HF ratio. Some patients also received systemic therapies alongside radiotherapy; thus, patients were subdivided into a radiotherapy-only group (28 cases) and a combined radiotherapy and systemic therapies group (30 cases) for additional subgroup analysis.ResultsThoracic radiotherapy resulted in a significant reduction in DC (8.5 [5.0, 14.2] vs. 5.3 [3.5, 9.4], p = 0.002) and HRV parameters SDNN (9.9 [7.03, 16.0] vs. 8.2 [6.0, 12.4], p = 0.003), RMSSD (9.9 [6.9, 17.5] vs. 7.7 [4.8, 14.3], p = 0.009), LF (29 [10, 135] vs. 24 [15, 50], p = 0.005), HF (35 [12, 101] vs. 16 [9, 46], p = 0.002), TP (74 [41, 273] vs. 50 [33, 118], p

BackgroundDuplication of the transverse colon is a rare gastrointestinal malformation. Its pathogenesis is still unclear, and it is extremely rare in adults. Patients often present with symptoms of tumor compression such as abdominal mass, abdominal pain, and constipation as the first manifestation.Methods and resultA patient with a duplication of the transverse colon was admitted to the Department of General Surgery of our hospital. Laparoscopic exploration found a mass at the rear of the transverse colon near the splenic flexure, and the root was connected to the middle portion of the transverse colon.ConclusionSurgery is a radical treatment and reduces the possibility of perforation, bleeding, obstruction, and cancer.

ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent causing the global pandemic of COVID-19. SARS-CoV-2 genome encodes a main protease (nsp5, also called Mpro) and a papain-like protease (nsp3, also called PLpro), which are responsible for processing viral polyproteins to assemble a functional replicase complex. In this study, we found that Mpro of SARS-CoV-2 can cleave human MAGED2 and other mammalian orthologs at Gln-263. Moreover, SARS-CoV and MERS-CoV Mpro can also cleave human MAGED2, suggesting MAGED2 cleavage by Mpro is an evolutionarily conserved mechanism of coronavirus infection in mammals. Intriguingly, Mpro from Beta variant cleaves MAGED2 more efficiently than wild type, but Omicron Mpro is opposite. Further studies show that MAGED2 inhibits SARS-CoV-2 infection at viral replication step. Mechanistically, MAGED2 is associated with SARS-CoV-2 nucleocapsid protein through its N-terminal region in an RNA-dependent manner, and this disrupts the interaction between SARS-CoV-2 nucleocapsid protein and viral genome, thus inhibiting viral replication. When MAGED2 is cleaved by Mpro, the N-terminal of MAGED2 will translocate into the nucleus, and the truncated MAGED2 is unable to suppress SARS-CoV-2 replication. This work not only discovers the antiviral function of MAGED2 but also provides new insights into how SARS-CoV-2 Mpro antagonizes host antiviral response. IMPORTANCE Host factors that restrict severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain elusive. Here, we found that MAGED2 can be cleaved by SARS-CoV-2 main protease (Mpro) at Gln-263. SARS-CoV and MERS-CoV Mpro can also cleave MAGED2, and MAGED2 from multiple species can be cleaved by SARS-CoV-2 Mpro. Mpro from Beta variant cleaves MAGED2 more efficiently efficiently than wild type, but Omicron is the opposite. MAGED2 depletion enhances SARS-CoV-2 infection, suggesting its inhibitory role in SARS-CoV-2 infection. Mechanistically, MAGED2 restricts SARS-CoV-2 replication by disrupting the interaction between nucleocapsid and viral genomes. When MAGED2 is cleaved, its N-terminal will translocate into the nucleus. In this way, Mpro relieves MAGED2' inhibition on viral replication. This study improves our understanding of complex viral-host interaction and provides novel targets to treat SARS-CoV-2 infection.

Doumei 1 is a new cultivar of faba bean (Vicia faba L.) jointly bred by Chongqing Academy of Agricultural Sciences, Qinghai University, and Chongqing Agricultural Technology Extension Station. It has both horticultural and food functions. The flower color of this cultivar is pink and bright, with determinate inflorescence (Fig. 1A). During autumn sowing, the flowering period is ≈40 d in the field. ‘Doumei’ 1 is a new high-value horticulture crop (Fig. 2); the secondary branches are obvious (Fig. 1B), and it is suitable for mechanized harvesting because of its podding habit, with podding on the middle and upper nods (Fig. 1B). The emergence of faba bean cultivars with both horticultural and edible functions has endowed the traditional faba bean planting industry with landscape functions. This is essential for cross-industry innovation in faba bean breeding.

Background: Signal transducers and activators of transcription (STAT) proteins, well-known cytoplasmic transcription factors, were found to be abnormally expressed in various cancers and play essential parts in the initiation, progression and therapy resistance of cancer. Nevertheless, the functions of different STATs in pancreatic cancer (PC) and their relationship to the prognosis and immune infiltration as well as drug efficacy in PC patients have not been systematically elucidated. Methods: Expression, prognosis, genetic alterations and pathway enrichment analyses of the STAT family were investigated via Oncomine, GEPIA, Kaplan Meier-plotter, cBioPortal, Metascape and GSEA. Analysis of tumor immune microenvironment was conducted by ESTIMATE and TIMER. “pRRophetic” packages were used for analysis of chemotherapeutic response. Finally, the diagnostic and prognostic value of key STATs were further validated through public datasets and immunohistochemistry. Results: In this study, only STAT1 mRNA level was significantly increased in tumor tissues and highly expressed in PC cell lines via multiple datasets. PC patients with higher STAT1/4/6 expression had a worse overall survival (OS) and progression-free survival (PFS), while higher STAT5B expression was correlated with better prognosis in the TCGA cohort. The STATs-associated genes were enriched in pathways about the remodeling of tumor immune microenvironment. The STATs levels were significantly correlated with immune infiltration, except STAT6. The STAT1 was identified as a potential biomarker and its diagnostic and prognostic value were further validated at mRNA and protein levels. GSEA showed that STAT1 may be involved in the progression and immune regulations of PC. Moreover, STAT1 expression was significantly related to the level of immune checkpoint, and predicted immunotherapy and chemotherapy responses. Conclusion: STAT family members were comprehensively analyzed and STAT1 was identified as an effective biomarker for predicting the survival and therapeutic response, which could be beneficial to develop better treatment strategies.

Background: PD-1 blockade has been shown to have promising efficacy and acceptable safety profiles in advanced and metastatic gastric cancer; however, the efficacy and safety of neoadjuvant PD-1 blockade-based immunotherapy plus chemotherapy in locally advanced gastric cancer (LAGC) remain uncertain. Methods: We performed a retrospective review of patients with LAGC who received neoadjuvant treatment followed by D2 radical resection at the Affiliated Hospital of Qingdao University from 2019 to 2021. The primary aim was to investigate the difference in pathological response rates between neoadjuvant PD-1 immunotherapy plus chemotherapy and neoadjuvant chemotherapy alone. Multivariable models for pathological complete response (pCR) were constructed to investigate the factors that facilitate pCR. Trial registration: QYFYWZLL27406. Results: A total of 77 patients were included in the analysis, among whom 34 (44.2%) received neoadjuvant PD-1 blockade immunotherapy plus chemotherapy. A higher pCR rate was observed in the neoadjuvant PD-1 blockade immunotherapy plus chemotherapy group (8 of 34, 23.5% vs. 2 of 43, 4.7%, P=0.019). Multivariate logistic regression analysis of pCR revealed neoadjuvant PD-1 blockade plus chemotherapy regimen promoted pCR (OR 12.95, P=0.016). Regarding safety, 76.5% (26 of 34) of patients in the PD-1 blockade plus chemotherapy group and 76.7% (33 of 43) of patients in the chemotherapy group experienced treatment-related adverse events (TRAEs), and grade 3 or worse adverse events were 29.4% (10 of 34) and 34.9% (15 of 43), respectively. Conclusion: Neoadjuvant PD-1 blockade plus chemotherapy induced a higher pCR rate than neoadjuvant chemotherapy, and the combined therapy was tolerable in LAGC patients.

BackgroundPrevious studies have shown that the predictive value of traditional linear (time domain and frequency domain) heart rate variability (HRV) for the survival of patients with advanced non-small cell lung cancer (NSCLC) is controversial. Nonlinear methods, based on the concept of complexity, have been used to evaluate HRV, providing a new means to reveal the physiological and pathological changes in HRV. This study aimed to assess the association between heartbeat complexity and overall survival in patients with advanced NSCLC.MethodsThis study included 78 patients with advanced NSCLC (mean age: 62.0 ± 9.3 years). A 5-min resting electrocardiogram of advanced NSCLC patients was collected to analyze the following HRV parameters: time domain indicators, i.e., standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD); frequency domain indicators, i.e., total power (TP), low frequency power (LF), high frequency power (HF), and the ratio of LF to HF (LF/HF); nonlinear HRV indicators characterizing heartbeat complexity, i.e., approximate entropy (ApEn), sample entropy (SampEn), and recurrence quantification analysis (RQA) indexes: mean diagonal line length (Lmean), maximal diagonal line length (Lmax), recurrence rate (REC), determinism (DET), and shannon entropy (ShanEn).ResultsUnivariate analysis revealed that the linear frequency domain parameter HF and nonlinear RQA parameters Lmax, REC, and DET were significantly correlated with the survival of advanced NSCLC patients (all p

The abscisic acid (ABA) receptor PYR/PYL/RCAR, located upstream of the ABA signaling pathway, recognizes ABA signals and initiates the primary process of signal transduction. In our previous study, we found that the PYL4 gene in tomato plants was significantly upregulated after exogenous treatment with the hormone ABA. The present study used virus-induced gene silencing (VIGS) to further elucidate the role of the PYL4 gene in response to drought in tomato (Solanum lycopersicum) plants. Under the drought treatment, the SlPYL4-silenced plants wilted faster than the control plants did. Physiological indicators showed that the total reactive oxygen species (ROS) content and superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) activities of the SlPYL4-silenced plants were lower than those of the control plants after 3 and 6 h of drought stress treatment. After 3 h of drought treatment, hydrogen peroxide (H2O2) and superoxide anion (O2−.) accumulated much more in the leaves of the SlPYL4-silenced plants than in the leaves of the control plants. These results indicated that PYL4 plays a positive role in drought tolerance in tomato plants. Our results also suggest that SlPYL4 is located upstream of the ABA pathway to regulate the expression of PP2C, SnRK, and AREB/ABF genes.

CRISPR-Cas9 is a common tool for gene editing, and appropriate sgRNAs are the key factor for successful editing. In this study, the effect of sgRNA length and number on editing efficiency was analyzed in rice using CYP81A6 as the target gene. A series of CRISPR-Cas9 plant expression vectors containing single sgRNAs with different lengths (17, 18, 19, 20, 21, 22, 23 nt) or two sgRNAs were constructed and introduced into rice cultivar Zhonghua11 by Agrobacterium-mediated transformation. Analysis of the editing status of 1283 transgenic rice plants showed that 371 were successfully edited with base preference. Single A or T insertions were the most frequent among the six edited types. The editing efficiency of transgenic rice with two sgRNAs was higher than that with a single sgRNA. Editing efficiency and sgRNA length showed a normal distribution with 20 nt sgRNA (25%) being the most efficient. The editing efficiency decreased slightly with decreases of 1–2 bases (19 nt 20%, 18 nt 21%), but decreased significantly with a decrease of 3 bases (17 nt 4.5%). Editing efficiency was significantly reduced by adding 1 to 3 bases (21 nt 16.8%, 22 nt 13%, 23 nt 13%) to the sgRNA. These results provide data for successful gene editing or rice by CRISPR-Cas9.

Background: Device-related thrombosis (DRT) after successful closure implantation on left atrial appendage (LAA) was considered as a major challenge and optimal strategy on antithrombotic therapy remains to be solved. This study was performed to compare the clinical effectiveness and safety of reduced rivaroxaban dose (RRD) and dual antiplatelet therapy (DAPT) after left atrial appendage closure (LAAC) implantation with the Watchman device. Methods: After successful LAAC, consecutive participants were medicated with a standard DAPT or RRD. The primary endpoints included DRT, thrombosis events (TE), and bleeding events that were documented during a 12-month follow-up period. Results: 767 patients (DAPT: n = 140; RRD: n = 627) were initially included. After propensity score matching (PSM), 140 patients treated with DAPT and 280 patients with RRD were included in each group with similar baseline information, thromboembolic and bleeding risk factors, cardiovascular risk factors and concomitant medication. In the RRD group, 193 patients were on rivaroxaban 15 mg (R15) and 47 received rivaroxaban 10 mg (R10). The incidence of DRT was documented in 12 (9.3%) patients in the DAPT group and 3 (6.3%) in R10 and 7 (3.0%) in R15 (log-rank p = 0.050). DAPT subgroups were more likely to experience shorter time to DRT as compared to R15 (R15vs. DAPT hazard ratio (HR) = 0.334, p = 0.015, 95% CI: 0.131–0.850). The median length of DRT in the R15 group was significantly lower than that of the DAPT group (1.721 [1.610–1.818] mm vs. 1.820 [1.725–1.925] mm, p = 0.029). Compared with the unadjusted estimated rates of ischemic events for patients with similar congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack or thromboembolism, vascular disease, age 65–74 years, sex category (CHA2DS2-VASc) scores, a significant decrease of 68.6% in ischemic stroke rates was noted in the R15 group, which contributed to a 54.9% reduction of overall thromboembolic events. The overall minor bleeding was not significantly different amongst the three groups (p = 0.944). Procedural bleeding was more common in the DAPT group, as compared with the R10 and R15 groups. Conclusions: After successful closure implantation, long-term RRD significantly reduced the DRT and TE occurrence compared with DAPT.

In the southeastern coastal regions of China, thick layers of marine soft soil are widely distributed, exhibiting characteristics such as high compressibility, high porosity, low strength, high sensitivity, and easy thixotropy, and these viscoelastic behaviors of foundation soil have significant implications for elastic compression bending bar, as evidenced by issues such as post-construction settlement of roadbeds and long-term operation deviation of bridge pile foundations. In this study, a mechanical model of an elastic bar embedded in an elastic and viscoelastic medium, fixed at the base and free at the top, is established based on the Winkler foundation assumption. The deflection function of a bar subjected to both axial force and locally distributed horizontal load is derived using the Rayleigh-Ritz method. Utilizing the elastic-viscoelastic correspondence principle, the viscoelastic medium surrounding the bar is modeled as an elastic medium in which the ground reaction coefficient varies within phase space formulation. This study provides a robust theoretical foundation for soft soil foundation engineering projects and fills a significant gap in the literature by offering a comprehensive framework for understanding displacement in elastic bars within viscoelastic media. Drawing upon the derivation of the deformation function for elastic rods within a viscoelastic medium, the findings of this research hold significant applicability across a range of domains. These include, but are not limited to, the expansion of roadways in regions characterized by coastal soft soil, as well as the monitoring of deformation and lifespan in bridge pile foundations.

A growing body of evidence suggests that the increase of permeability results in reduced strength and bearing capacity of subgrade. A new microbiological stabilizing method, known as microbial induced calcite precipitation (MICP), was induced into stabilization of the subgrade for fully permeable pavement in this study. This study explored the mechanical and hydraulic properties of unsaturated and saturated fine sand soil stabilized by MICP technology. Instead of bacteria, urease was directly induced into fine sand with pre-mixing method. The results indicated that saturated specimens obtained better moisture stability. Compared with cement stabilized soil, the compressive strength and resilient modulus of unsaturated urease stabilized soil were lower under the same CaCO3 or cement content. What stands out in this study is that the saturated urease stabilized soil was not sensitive to water and had relatively higher strength. In addition, the hydraulic conductivity of urease stabilized soil was significantly higher than that of cement stabilized soil. This study developed a potential subgrade improvement technology for possible application in fully permeable pavement. Urease stabilizing method could be used to help increase the strength and maintain a high hydraulic conductivity.

Abstract Background Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small‐scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first‐line treatment in locally advanced or metastatic LSCC. Methods Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression‐free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45‐Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses. Results The median duration of follow‐up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF‐α, IFN‐γ, IL‐6, and IL‐8, demonstrating an overlapping trend. Conclusion The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen.

Abstract Delayed luminescence (DL) is gradually used in various detection of biological systems as a rapid detection technique, however, its biological mechanism was still not clear. In this study, a new model of DL detection system for liquid biological samples is established to investigate the DL emission of Saccharomyces cerevisiae cells cultured in different glucose concentrations. We analyzed the relationship between the DL emission and cell growth, cell vitality, mitochondrial morphology, mitochondrial DNA (mtDNA) copy number, adenosine triphosphate (ATP), oxygen consumption rate (OCR), as well as mitochondria membrane potential (MMP) in S. cerevisiae cells cultured with 0.01, 0.05, 0.15, 3, 10 and 20 g/L glucose respectively. It was found that the DL emission had strong correlation with mitochondrial morphology, OCR, and MMP. The results suggested that DL is an indicator of mitochondria status under different glucose supply conditions, and may be an effective method to detect mitochondrial metabolism related disorders.

Despite the fact that task-oriented conversation systems have received much attention from the dialogue research community, only a handful of them have been studied in a real-world manufacturing context using industrial robots. One stumbling block is the lack of a domain-specific discourse corpus for training these systems. Another difficulty is that earlier attempts to integrate natural language interfaces (such as chatbots) into the industrial sector have primarily focused on task completion rates. When designing a dialogue system for social robots, the user experience is prioritized above industrial robots. To overcome these challenges, we provide the Industrial Robots Domain Wizard-of-Oz dataset (IRWoZ), a fully-labeled discourse dataset covering four robotics domains. It delivers simulated discussions between shop floor workers and industrial robots, with over 401 dialogues, to promote language-assisted Human-Robot Interaction (HRI) in industrial settings. Small talk concepts and human-to-human conversation strategies are provided to support human-like answer generation and give a more natural and adaptable dialogue environment to increase user experience and engagement. Finally, we propose and evaluate an end-to-end Task-oriented Dialogue for Industrial Robots (ToD4IR) using two types of pre-trained backbone models: GPT-2 and GPT-Neo, on the IRWoZ dataset. We performed a series of trials to validate ToD4IR’s performance in a real manufacturing context. Our experiments demonstrate that ToD4IR outperforms three downstream task-oriented dialogue tasks, i.e., dialogue state tracking, dialogue act generation, and response generation, on the IRWoZ dataset. Our source code of ToD4IR and the IRWoZ dataset is accessible at https://github.com/lcroy/ToD4IR for reproducible research.