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Abstract High-grade serous ovarian cancer (HGSOC) is an aggressive disease known to develop resistance to chemotherapy. We investigated the prognostic significance of tumor cell states and potential mechanisms underlying chemotherapy resistance in HGSOC. Transcriptome deconvolution was performed to address cellular heterogeneity. Kaplan–Meier survival curves were plotted to illustrate the outcomes of patients with varying cellular abundances. The association between gene expression and chemotherapy response was tested. After adjusting for surgery status and grading, several cell states exhibited a significant correlation with patient survival. Cell states can organize into carcinoma ecotypes (CE). CE9 and CE10 were proinflammatory, characterized by higher immunoreactivity, and were associated with favorable survival outcomes. Ratios of cell states and ecotypes had better prognostic abilities than a single cell state or ecotype. A total of 1265 differentially expressed genes were identified between samples with high and low levels of C9 or CE10. These genes were partitioned into three co-expressed modules, which were associated with tumor cells and immune cells. Pogz was identified to be linked with immune cell genes and the chemotherapy response of paclitaxel. Collectively, the survival of HGSOC patients is correlated with specific cell states and ecotypes.

Abstract How to prevent and resolve COVID-19 pandemic and similar public health crisis is a significant research topic. Although research on science literacy has been involved in dealing with public health crisis, there is a lack of empirical tests between the mass public’s science literacy and co-production during COVID-19 pandemic. With the empirical evidence from 140 cities in China, the study finds that the public’s science literacy significantly promotes co-production in the battle against pandemic. Specifically, for every 1% increase in the mass public’s science literacy in the city, co-production increased by 14.2%. Meanwhile, regional education level and local government capacity can expand the positive role of the public’s science literacy on co-production to fight against COVID-19 pandemic. In addition, the performance of the public’s science literacy on co-production against pandemic shows heterogeneity at different stages of pandemic prevention, in different regions, and in cities of different scales. This study complemented the gaps in existing research on science literacy and co-production and empirically verified the potential positive role of the public’s science literacy in pandemic prevention and control. Furthermore, it provided new ideas for improving the effectiveness of public co-production in public health crisis governance.

Abstract Video frame interpolation (VFI) is a technique that synthesises intermediate frames between adjacent original video frames to enhance the temporal super‐resolution of the video. However, existing methods usually rely on heavy model architectures with a large number of parameters. The authors introduce an efficient VFI network based on multiple lightweight convolutional units and a Local three‐scale encoding (LTSE) structure. In particular, the authors introduce a LTSE structure with two‐level attention cascades. This design is tailored to enhance the efficient capture of details and contextual information across diverse scales in images. Secondly, the authors introduce recurrent convolutional layers (RCL) and residual operations, designing the recurrent residual convolutional unit to optimise the LTSE structure. Additionally, a lightweight convolutional unit named separable recurrent residual convolutional unit is introduced to reduce the model parameters. Finally, the authors obtain the three‐scale decoding features from the decoder and warp them for a set of three‐scale pre‐warped maps. The authors fuse them into the synthesis network to generate high‐quality interpolated frames. The experimental results indicate that the proposed approach achieves superior performance with fewer model parameters.

In this study, WC-12Co cemented carbides were prepared by laser powder bed fusion (LPBF) on a WC-20Co substrate. The effects of the scanning speed and the substrate on the microstructure, mechanical properties and wear characteristics of the WC-12Co cemented carbide were investigated. The results showed that an alternating distribution of coarse and fine WC grains is observed in the LPBF-prepared WC-12Co cemented carbides. As the laser scanning speed decreases or the laser energy density increases, the WC phase gradually decomposes, accompanied by the loss of C and the formation of ƞ phases. WC-12Co cemented carbides produced at a lower scanning speed exhibit a higher density of thermal cracks, while those produced at a higher scanning speed have a larger number of pores. As the laser scanning speed increases, the transverse rupture strength (TRS) first increases to a maximum value of 823.13 MPa and then decreases. The variation of TRS is mainly attributed to the evolution of the brittle ƞ-phase and metallurgical defects. For WC-12Co cemented carbides formed at low scanning speeds, the brittle η-phase may fracture and cut through the matrix during the friction process, leading to an increase in coefficient of friction (COF) and wear mass loss. For samples formed at high scanning speeds, the formation and detachment of the shear layer could accelerate the friction process and undermine the wear resistance of the WC-12Co cemented carbide. Therefore, the sample prepared at the scanning speed of 400 mm/s shows the best wear performance.

Abstract The rise in sea levels, driven by global climate change, poses a significant threat to cultural heritage in coastal regions. Traditional risk assessment methods, focusing on direct inundation, often fail to consider the crucial impact of socio-economic factors, which are significantly vulnerable to sea level rise. To bridge this gap, this study introduces an innovative Sea Level Rise Cultural Heritage Impact Assessment Model (SLR-CHIA Model), a novel approach that integrates both land inundation and socio-economic aspects. This comprehensive model evaluates potential risks to various types of cultural heritage in coastal China, including intangible cultural heritage, relics, and traditional villages. The study’s findings are striking: (1) About 7.79% of coastal villages, 53.94% of relics, and 2.53% of intangible cultural heritage are potentially at high risk in a 100-year sea level rise event; (2) Relics in the Eastern coast and villages in the Southern coast are most vulnerable; (3) Different types of cultural heritage rely on diverse principal factors for protection, resulting in varied risk levels under sea level rise conditions. The SLR-CHIA Model provides a vital methodological framework for evaluating cultural heritage risks in other global regions.

Sepsis, a systemic inflammatory response caused by infection, can lead to sepsis-associated encephalopathy (SAE), characterized by brain dysfunction without direct central nervous system infection. The pathogenesis of SAE involves blood-brain barrier disruption, neuroinflammation and neuronal death, with neuroinflammation being the core process. Nogo-A, a neurite growth-inhibitory protein in the central nervous system, is not well understood in sepsis. This study explores Nogo-A's mechanisms in sepsis, focusing on SAE. Using in vivo and in vitro methods, healthy SPF C57BL/6J male mice were divided into Sham, Nogo-A-NC-Model, and Nogo-A-KD-Model groups, with sepsis induced by abdominal ligation and puncture. Morris water maze tests assessed learning and memory, and brain tissues underwent HE staining, Nissl staining, and Western blot analysis. In vitro, Nogo-A gene knockdown models were constructed using BV-2 microglia cells to study inflammation and oxidative stress. Results showed Nogo-A expression affected learning and memory in septic mice, with knockdown reducing neuronal damage. Bioinformatics analysis suggested Nogo-A may activate ROS to inhibit p-SHP2, activating mitochondrial autophagy and promoting neuronal apoptosis. Western blot results confirmed that Nogo-A affects mitochondrial autophagy and neuronal survival by inhibiting SHP2 and activating ROS. Nogo-A's role in neuroinflammation and neuroprotection was emphasized, revealing its impact on ER stress, mitochondrial autophagy, and NLRP3 inflammasome activation. This study provides a theoretical basis for SAE treatment, suggesting further multi-gene and multi-pathway analyses and validation in clinical samples. Developing gene therapy and drug interventions targeting Nogo-A pathways will offer more effective treatment strategies.

Diabetic gastroparesis, a common complication of type 2 diabetes (T2DM), presents a significant treatment challenge. FoxiangSan is emerging as a potential therapy. FoxiangSan is a traditional Chinese medicine formula with the potential for treating diabetic gastroparesis by modulating gut microbiota and cAMP/PKA signaling pathways. This study explores the mechanisms behind FoxiangSan's effects on T2DM-induced gastroparesis, focusing on its impact on gut microbiota and the cAMP/PKA pathway. A rat model of type 2 diabetic gastroparesis was established through a high-fat diet and streptozotocin (STZ) injection, and the effects of FoxiangSan were assessed. Additionally, protein expression related to the cAMP/PKA pathway was examined, and FoxiangSan's influence on gut microbiota was studied using 16S rRNA sequencing. FoxiangSan significantly alleviated hyperglycemia, improved gastric pathology in rats with gastroparesis, enhanced the expression of 5-HT4, cAMP, PKA, and pPKA in the gastric antrum, and rebalanced gut microbiota. FoxiangSan demonstrates the therapeutic potential for T2DM-associated gastroparesis by modulating the cAMP/PKA pathway and gut microbiota.

Limb-girdle muscular dystrophy type 2A (LGMD R1 Calpain 3-Related, LGMD2A/R1), an autosomal recessive disorder, is characterized by progressive muscle weakness with a prominent presentation in the proximal limb girdle muscles. LGMD2A/R1, which is caused by variants in calcium-activated neutral proteinase 3 (CAPN3), is the most common. The present study aimed at identifying the clinically significant variants in a Chinese family with LGMD2A/R1 and exploring the genotype–phenotype correlations. Clinical symptoms, laboratory findings, and physical examinations were obtained. Genomic DNA was extracted from the peripheral blood samples of this family. Whole-exome sequencing (WES) and Sanger sequencing were used to explore and validate the pathogenic genes. In this study, the proband and his sister, who had two identical mutations in the CAPN3 gene sequence, exhibited diverse clinical features, including disease onset and progression. The mutation c.2120 A>G (p. D707G) is pathogenic and has been reported in the Human Gene Mutation Database (HGMD) and the ClinVar database. c.1783-72 C>G may be a novel pathogenic mutation of LGMD2A/R1 based on the American College of Medical Genetics (ACMG) guidelines, which widens the gene variant pool in CAPN3 and improves diagnosis and genetic counseling.

Abstract Developing efficient electrocatalysts with low‐cost for the urea oxidation reaction (UOR) is a significant challenge in energy‐saving H2 production owing to its lower thermodynamic potential. Heteroatom incorporation strategy has been proven to boost electrocatalytic activity by altering electronic structures and revealing more active sites on catalysts. Herein, nickel hydroxide nanosheets with various vanadium incorporation (Vx‐Ni(OH)2) were developed through a facile hydrothermal approach. By optimizing the incorporated vanadium contents, V6‐Ni(OH)2 catalyst exhibited easily accessible active sites and enhanced charge transfer with structural advantages, then assembled as the working electrode for urea‐assisted H2 production. Consequently, V6‐Ni(OH)2 catalyst demonstrated superior UOR activity compared with other incorporated samples with an overpotential of 1.33 V and a Tafel slope of 28.3 mV dec−1. Theoretical calculations revealed that the improved UOR activity was attributed to the potential determining step of V‐Ni(OH)2, which exhibited lower energy in comparison with the pristine Ni(OH)2 and increased electronic states density near the Fermi level. Both experimental and theoretical calculations confirmed vanadium incorporation on Ni(OH)2 could modify the electronic structure of Ni(III) species, improving electrical conductivity, and optimizing the adsorption energy for key reaction intermediates. Furthermore, the crucial contribution of vanadium incorporation with optimized electronic structures to the high UOR activity of Ni(OH)2 is demonstrated.

Path planning is an essential research topic in the navigation of mobile robots. Currently, rapidly-exploring random tree star (RRT*) and its variants are known for their probabilistic completeness and asymptotic optimality, making them effective in finding solutions for many path planning problems. However, slow convergence rate of the RRT* limits its practical efficiency. To address this problem, this paper proposed an enhanced RRT* algorithm by refining the extension process of the exploring tree. This enhancement aims to guide the tree approaching to obstacles (GAO) while exploring toward the target point. First, GAO-RRT* employed a dual-weighted sample strategy instead of random sample to guide search direction of the exploring tree. Second, a variable step size extension strategy was adopted to increase the efficiency of node generation, balancing searching time and path safety in regions with different obstacles densities. Third, growth status of new nodes was monitored in real-time, and a reverse growth strategy was proposed to guide the exploring tree to escape local optima. In addition, parent node creation procedure for new nodes was used to produce a better initial path. Finally, the proposed GAO-RRT* was compared with three state of the art algorithms on 16 different instances of four representative environments. Compared to RRT*, Quick-RRT* (Q-RRT*), and Fast-RRT* (F-RRT*), the results showed that (1) the average path cost of initial solutions obtained by GAO-RRT* decreased by 38.32%, 29.69%, and 20.44%, respectively; and (2) the average convergence time of solution obtained by GAO-RRT* to suboptimal (1.05*$ C_{best} $) was reduced by 71.22%, 69.69%, and 58.37%, respectively. Simulation results indicated that GAO-RRT* outperforms the compared algorithms in terms of path cost and convergence speed.

Abstract Background The cation/proton antiporter (CPA) superfamily plays a crucial role in regulating ion homeostasis and pH in plant cells, contributing to stress resistance. However, in potato (Solanum tuberosum L.), systematic identification and analysis of CPA genes are lacking. Results A total of 33 StCPA members were identified and classified into StNHX (n = 7), StKEA (n = 6), and StCHX (n = 20) subfamilies. StCHX owned the highest number of conserved motifs, followed by StKEA and StNHX. The StNHX and StKEA subfamilies owned more exons than StCHX. NaCl stress induced the differentially expression of 19 genes in roots or leaves, among which StCHX14 and StCHX16 were specifically induced in leaves, while StCHX2 and StCHX19 were specifically expressed in the roots. A total of 11 strongly responded genes were further verified by qPCR. Six CPA family members, StNHX1, StNHX2, StNHX3, StNHX5, StNHX6 and StCHX19, were proved to transport Na+ through yeast complementation experiments. Conclusions This study provides comprehensive insights into StCPAs and their response to NaCl stress, facilitating further functional characterization.

For the project of pipe jacking in cohesionless soil, it is key to determine the vertical load on jacked pipe so as to predict the jacking force accurately. In this paper, a new parabolic soil arching model was proposed to calculate the vertical load on jacked pipe. This proposed analytical model was composed of parabolic soil arching zone, parabola-typed collapse zone and friction arch zone. Combined with existing literature, the key parameters (i.e., height of parabolic soil arching, horizontal pressure coefficient and width and height of friction arch) were determined. In addition, considering that the trajectory of major stress is parabola, the formula of horizontal pressure coefficient was deduced in the friction arch. The parabolic soil arching zone is assumed as a three-hinged arch with reasonable arch axis, and the formula of load transfer was derived considering the transition effect of parabolic soil arching. The results of experiment, theoretical models and numerical model were adopted to verify the proposed analytical model. Finally, the influence of the key parameters on the vertical load on jacked pipe were also discussed in detail. This work provides a meaningful reference for evaluating the vertical load on jacked pipe for design of pipe jacking.

Abstract Background Salinity stress is an environmental constraint that normally develops concurrently under field conditions, resulting in drastic limitation of rice plant growth and grain productivity. The objective of this study was to explore the alleviating effects of NaCl pre-treatment on rice seedlings as well as the salt tolerance mechanisms by evaluating morph-physiological traits. Results Variety Huanghuazhan, either soaked in distilled water or 25 mg/L Prohexadione calcium (Pro-Ca), were first hardened with varying concentrations of NaCl solutions (0 and 50 mM NaCl), and then subjected to varying degrees of salt stress (0 and 100 mM NaCl), indicated by S0, S1, S2 and S3, respectively. Growth analysis suggested that NaCl-pretreatment improved the root/shoot ratio in water-soaked rice plant at DAP 0. Data related to the reaction center density, photosynthetic electron transport efficiency, trapping efficiency were compared before (CK) using performance Index (PIabs). Compared to S2 (Pro-Ca-S2) treatment, PIabs did not show any difference with plants pre-treated with NaCl (S3 or Pro-Ca-S3). Rather than PIabs, significant difference was found in photosynthetic electron transport efficiency (ΨEo). The ΨEo value in Pro-S2 was significantly lowered as compared to Pro-S3 treatment at DAP 7, and the decrease rate was about 6.5%. Correlation analysis indicated leaf PIabs was weak correlated with plant biomass while the quantum yield for reduction of the PSI end electron acceptors, trapped energy flux per reaction center and PSII antenna size displayed strong positive correlation with biomass. Additional analysis revealed that 100 mM NaCl significantly reduced leaf linear electron flux under low-light conditions, regardless of whether seedlings had been pre-treated with 50 mM NaCl or not. Conclusions NaCl-induced salt tolerance was related to the robust photosynthetic machinery.

Objective: The traditional Chinese patent medicine (TCPM), Simo decoction (Simo decoction oral solution), with its primary ingredient Arecae semen (Binglang, Areca catechu L.), known for its potential carcinogenic effects, is the subject of this study. The research aims to analyze the effectiveness and potential risks of Simo decoction, particularly as a carcinogen, and to suggest a framework for evaluating the risks and benefits of other herbal medicines. Methods: The study is based on post-marketing research of Simo decoction and Arecae semen. It utilized a wide range of sources, including ancient and modern literature, focusing on the efficacy and safety of Simo decoction. The research includes retrospective data on the sources, varieties, and toxicological studies of Arecae semen from databases such as Pubmed, Clinical Trials, Chinese Clinical Trial Registry, China National Knowledge Infrastructure, WHO-UMC Vigibase, and China National Center for ADR Monitoring. Results: Common adverse drug reactions (ADRs) associated with Simo decoction include skin rash, nausea, vomiting, abdominal pain, and diarrhea. However, no studies exist reporting the severe ADRs, such as carcinogenic effects. Arecae semen is distributed across approximately 60 varieties in tropical Asia and Australia. According to the WHO-UMC Vigibase and the National Adverse Drug Reaction Monitoring System databases, there are currently no reports of toxicity related to Arecae semen in the International System for Classification of ADRs (ISCR) or clinical studies. Conclusion: Risk-benefit analysis in TCPM presents more challenges compared to conventional drugs. The development of a practical pharmacovigilance system and risk-benefit analysis framework is crucial for marketing authorization holders, researchers, and regulatory bodies. This approach is vital for scientific supervision and ensuring the safety and efficacy of drug applications, thus protecting public health.

Halicin, the first antibacterial agent discovered by artificial intelligence, exerts broad-spectrum antibacterial effects and has a unique structure. Our study found that halicin had a good inhibitory effect on clinical isolates of drug-resistant strains and Clostridium perfringens (C. perfringens). The safety of halicin was evaluated by acute oral toxicity, genotoxicity and subchronic toxicity studies. The results of acute toxicity test indicated that halicin, as a low-toxicity compound, had an LD50 of 2018.3 mg/kg. The results of sperm malformation, bone marrow chromosome aberration and cell micronucleus tests showed that halicin had no obvious genotoxicity. However, the results of the 90-day subchronic toxicity test indicated that the test rats exhibited weight loss and slight renal inflammation at a high dose of 201.8 mg/kg. Teratogenicity of zebrafish embryos showed that halicin had no significant teratogenicity. Analysis of intestinal microbiota showed that halicin had a significant effect on the intestinal microbial composition, but caused a faster recovery. Furthermore, drug metabolism experiments showed that halicin was poorly absorbed and quickly eliminated in vivo. Our study found that halicin had a good therapeutic effect on intestinal infection model of C. perfringens. These results show the feasibility of developing oral halicin as a clinical candidate drug for treating intestinal infections.

Monitoring crop condition, soil properties, and mapping tillage activities can be used to assess land use, forecast crops, monitor seasonal changes, and contribute to the implementation of sustainable development policy. Agricultural maps can provide independent and objective estimates of the extent of crops in a given area or growing season, which can be used to support efforts to ensure food security in vulnerable areas. Satellite data can help detect and classify different types of soil. The evolution of satellite remote sensing technologies has transformed techniques for monitoring the Earth’s surface over the last several decades. The European Space Agency (ESA) and the European Union (EU) created the Copernicus program, which resulted in the European satellites Sentinel-1B (S1B) and Sentinel-2A (S2A), which allow the collection of multi-temporal, spatial, and highly repeatable data, providing an excellent opportunity for the study of land use, land cover, and change. The goal of this study is to map the land cover of Côte d’Ivoire’s West Central Soubre area (5°47′1′′ North, 6°35′38′′ West) between 2014 and 2020. The method is based on a combination of S1B and S2A imagery data, as well as three types of predictors: the biophysical indices Normalized Difference Vegetation Index “(NDVI)”, Modified Normalized Difference Water Index “(MNDWI)”, Normalized Difference Urbanization Index “(NDBI)”, and Normalized Difference Water Index “(NDWI)”, as well as spectral bands (B1, B11, B2, B3, B4, B6, B7, B8) and polarization coefficients VV. For the period 2014–2020, six land classifications have been established: Thick_Forest, Clear_Drill, Urban, Water, Palm_Oil, Bareland, and Cacao_Land. The Random Forest (RF) algorithm with 60 numberOfTrees was the primary categorization approach used in the Google Earth Engine (GEE) platform. The results show that the RF classification performed well, with outOfBagErrorEstimates of 0.0314 and 0.0498 for 2014 and 2020, respectively. The classification accuracy values for the kappa coefficients were above 95%: 96.42% in 2014 and 95.28% in 2020, with an overall accuracy of 96.97% in 2014 and 96 % in 2020. Furthermore, the User Accuracy (UA) and Producer Accuracy (PA) values for the classes were frequently above 80%, with the exception of the Bareland class in 2020, which achieved 79.20%. The backscatter coefficients of the S1B polarization variables had higher GINI significance in 2014: VH (70.80) compared to VH (50.37) in 2020; and VV (57.11) in 2014 compared to VV (46.17) in 2020. Polarization coefficients had higher values than the other spectral and biophysical variables of the three predictor variables. During the study period, the Thick_Forest (35.90% ± 1.17), Palm_Oil (57.59% ± 1.48), and Water (5.90% ± 0.47) classes experienced a regression in area, while the Clear_Drill (16.96% ± 0.80), Urban (2.32% ± 0.29), Bareland (83.54% ± 1.79), and Cacao_Land (35.14% ± 1.16) classes experienced an increase. The approach used is regarded as excellent based on the results obtained.

IntroductionThe hierarchical healthcare delivery system is an important measure to improve the allocation of medical resources and promote equitable distribution of basic medical and health services. It is one of the key factors in the success or failure of China’s medical reform. This study aims to analyze the factors influencing patients’ healthcare-seeking behaviors, including socioeconomic and clinical outcomes, under China’s hierarchical healthcare delivery system, and to provide potential solutions.MethodsPatients receiving outpatient treatment in the past 14 days and inpatient care in the past 1 year were investigated. The multivariate logistic regression was used to analyze the influencing factors of patient’s medical treatment behavior selection, and to compare whether the clinical outcomes of primary medical institutions and grade A hospitals are the same.ResultsNine thousand and ninety-eight person-times were included in the study. Of these, 4,538 patients were outpatients, 68.27% of patients were treated in primary medical institutions; 4,560 patients were hospitalized, 58.53% chose to be hospitalized in grade A hospitals. Provinces and cities, urban and rural areas, occupation, education level, medical insurance type, income, whether there are comorbid diseases, and doctors’ medical behavior are the factors affecting the choice of medical treatment behavior. Patients who choose primary medical institutions and grade A hospitals have different control levels and control rate for the blood pressure, blood lipids, blood glucose.ConclusionUnder the hierarchical diagnosis and treatment system, the patients’ choice of hospital is mainly affected by their level of education, medical insurance types, and the inpatients are also affected by whether there are comorbid conditions. Clinical outcomes of choosing different levels of hospitals were different.

Climate factors can impact the multifunctionality of steppe ecosystem by altering plant diversity. The pivotal role of diversity in mediating these effects is of paramount importance. Given that various facets of plant diversity exhibit diverse responses to climate change and impart distinct impacts on steppe ecosystem multifunctionality, the elucidation of how different dimensions of diversity mediate the effects of climate factors on steppe ecosystem multifunctionality assumes significance. The study area of this research was the typical steppe in Hulun Buir. Its main objective was to examine the direct and indirect impacts of climate factors on plant diversity and ecosystem multifunctionality. The findings showed that, in terms of the role played by climatic factors, precipitation had a greater effect on species diversity, while functional diversity and phylogenetic diversity were mainly influenced by temperature. The impact of climatic factors on below-ground ecosystem multifunctionality was notably substantial. With regard to the mediating role of plant diversity, species diversity played a greater role in moderating the effects of climatic factors on above- and below-ground ecosystem multifunctionality, while functional and phylogenetic diversity were important in mediating the effects of above- and below-ground ecosystem multifunctionality, respectively. To summarize, this study elucidates the correlation between multiple plant community diversities and ecosystem multifunctionality in a typical steppe under climate change, along with the potential mechanisms through which plant diversity moderates the influence of climate factors on ecosystem multifunctionality. Overall, species diversity and functional diversity take precedence over phylogenetic diversity, which can better predict the ecosystem multifunctionality of steppe and provide guidance for the conservation and sustainability of steppe plant diversity.

Abstract Background Immune dysregulation is a feature of sepsis. However, a comprehensive analysis of the immune landscapes in septic patients has not been conducted. Objectives This study aims to explore the abundance ratios of immune cells in sepsis and investigate their clinical value. Methods Sepsis transcriptome data sets were downloaded from the NCBI GEO database. The immunedeconv R package was employed to analyze the abundance of immune cells in sepsis patients and calculate the ratios of different immune cell types. Differential analysis of immune cell ratios was performed using the t test. The Spearman rank correlation coefficient was utilized to find the relationships between immune cell abundance and pathways. The prognostic significance of immune cell ratios for patient survival probability was assessed using the log-rank test. In addition, differential gene expression was performed using the limma package, and gene co-expression analysis was executed using the WGCNA package. Results We found significant changes in immune cell ratios between sepsis patients and healthy controls. Some of these ratios were associated with 28-day survival. Certain pathways showed significant correlations with immune cell ratios. Notably, six immune cell ratios demonstrated discriminative ability for patients with systemic inflammatory response syndrome (SIRS), bacterial sepsis, and viral sepsis, with an Area Under the Curve (AUC) larger than 0.84. Patients with a high eosinophil/B.cell.memory ratio exhibited poor survival outcomes. A total of 774 differential genes were identified in sepsis patients with a high eosinophil/B.cell.memory ratio compared to those with a low ratio. These genes were organized into seven co-expression modules associated with relevant pathways, including interferon signaling, T-cell receptor signaling, and specific granule pathways. Conclusions Immune cell ratios eosinophil/B.cell.memory and NK.cell.activated/NK.cell.resting in sepsis patients can be utilized for disease subtyping, prognosis, and diagnosis. The proposed cell ratios may have higher prognostic values than the neutrophil-to-lymphocyte ratio (NLR).

Abstract Background Gene knock‐in (KI) in animal cells via homology‐directed repair (HDR) is an inefficient process, requiring a laborious work for screening from few modified cells. HDR tends to occur in the S and G2/M phases of cell cycle; therefore, strategies that enhance the proportion of cells in these specific phases could improve HDR efficiency. Results We used various types of cell cycle inhibitors to synchronize the cell cycle in S and G2/M phases in order to investigate their effect on regulating CRISPR/Cas9-mediated HDR. Our results indicated that the four small molecules—docetaxel, irinotecan, nocodazole and mitomycin C—promoted CRISPR/Cas9-mediated KI with different homologous donor types in various animal cells. Moreover, the small molecule inhibitors enhanced KI in animal embryos. Molecular analysis identified common signal pathways activated during crosstalk between cell cycle and DNA repair. Synchronization of the cell cycle in the S and G2/M phases results in CDK1/CCNB1 protein accumulation, which can initiate the HDR process by activating HDR factors to facilitate effective end resection of CRISPR-cleaved double-strand breaks. We have demonstrated that augmenting protein levels of factors associated with the cell cycle via overexpression can facilitate KI in animal cells, consistent with the effect of small molecules. Conclusion Small molecules that induce cell cycle synchronization in S and G2/M phases promote CRISPR/Cas9-mediated HDR efficiency in animal cells and embryos. Our research reveals the common molecular mechanisms that bridge cell cycle progression and HDR activity, which will inform further work to use HDR as an effective tool for preparing genetically modified animals or for gene therapy.

This study delves into the multifaceted effects of multi-walled carbon nanotubes (MWCNT) incorporation on phosphogypsum's properties. We investigated the phase composition and morphology of phosphogypsum and observed the influence of MWCNT on the setting time, flexural strength, compressive strength, water resistance, and hydration process. The results demonstrated that MWCNT significantly abbreviates the setting time of phosphogypsum, enhances its absolute dry flexural strength and compressive strength, and improves water resistance, with optimal effects occurring at a MWCNT content of around 1.00%. Nonetheless, these benefits diminish and can even be counterproductive if MWCNT content is excessively high. The enhanced properties of phosphogypsum upon MWCNT addition can be ascribed to the filling effect and mechanical interlocking facilitated by MWCNT. Additionally, MWCNT promoted the hydration of phosphogypsum, as evidenced by calorimetric measurements.

Background: Robot grasping encompasses a wide range of research areas; however, most studies have been focused on the grasping of only stationary objects in a scene; only a few studies on how to grasp objects from a user's hand have been conducted. In this paper, a robot grasping algorithm based on deep reinforcement learning (RGRL) is proposed. Methods: The RGRL takes the relative positions of the robot and the object in a user's hand as input and outputs the best action of the robot in the current state. Thus, the proposed algorithm realizes the functions of autonomous path planning and grasping objects safely from the hands of users. A new method for improving the safety of human–robot cooperation is explored. To solve the problems of a low utilization rate and slow convergence of reinforcement learning algorithms, the RGRL is first trained in a simulation scene, and then, the model parameters are applied to a real scene. To reduce the difference between the simulated and real scenes, domain randomization is applied to randomly change the positions and angles of objects in the simulated scenes at regular intervals, thereby improving the diversity of the training samples and robustness of the algorithm. Results: The RGRL's effectiveness and accuracy are verified by evaluating it on both simulated and real scenes, and the results show that the RGRL can achieve an accuracy of more than 80% in both cases. Conclusions: RGRL is a robot grasping algorithm that employs domain randomization and deep reinforcement learning for effective grasping in simulated and real scenes. However, it lacks flexibility in adapting to different grasping poses, prompting future research in achieving safe grasping for diverse user postures.

Abstract Background Dysregulated epithelial–mesenchymal transition (EMT) is involved in cervical cancer metastasis and associated with histone acetylation. However, the underlying molecular mechanisms of histone acetylation in cervical cancer EMT and metastasis are still elusive. Methods We systematically investigated the expression patterns of histone acetylation genes and their correlations with the EMT pathway in cervical cancer. The expression of CSRP2BP among cervical cancer tissues and cell lines was detected using Western blotting and immunohistochemistry analyses. The effects of CSRP2BP on cervical cancer cell proliferation and tumorigenicity were examined by cell growth curve, EdU assay, flow cytometry and xenotransplantation assays. Wound healing assays, transwell migration assays and pulmonary metastasis model were used to evaluate the effects of CSRP2BP on cell invasion and metastasis of cervical cancer cells in vivo and in vitro. RNA-seq, chromatin immunoprecipitation (ChIP), co-immunoprecipitation (Co-IP) and luciferase reporter assays were used to uncover the molecular mechanisms of CSRP2BP in promoting cervical cancer EMT and metastasis. Results We prioritized a top candidate histone acetyltransferase, CSRP2BP, as a key player in cervical cancer EMT and metastasis. The expression of CSRP2BP was significantly increased in cervical cancer tissues and high CSRP2BP expression was associated with poor prognosis. Overexpression of CSRP2BP promoted cervical cancer cell proliferation and metastasis both in vitro and in vivo, while knockdown of CSRP2BP obtained the opposite effects. In addition, CSRP2BP promoted resistance to cisplatin chemotherapy. Mechanistically, CSRP2BP mediated histone 4 acetylation at lysine sites 5 and 12, cooperated with the transcription factor SMAD4 to bind to the SEB2 sequence in the N-cadherin gene promotor and upregulated N-cadherin transcription. Consequently, CSRP2BP promoted cervical cancer cell EMT and metastasis through activating N-cadherin. Conclusions This study demonstrates that the histone acetyltransferase CSRP2BP promotes cervical cancer metastasis partially through increasing the EMT and suggests that CSRP2BP could be a prognostic marker and a potential therapeutic target for combating cervical cancer metastasis.

Dragon fruits have abundant nutritional and antioxidant properties. High temperatures limit the growth and production of dragon fruits. Hemin can effectively alleviate abiotic stress in plants. However, the regulatory effect of Hemin on dragon fruit under heat stress remains unclear. In this study, we explored the impacts of foliar application of Hemin on dragon fruit size, yield and quality during the high temperatures of the summer season. In this experiment, dragon fruit variety ‘Jindu No. 1’ was used as material and treated with three Hemin concentrations, i.e., H1: 1 μmol.L−1, H2: 10 μmol.L−1, H3: 100 μmol.L−1, compared with CK: control. The results show that exogenous Hemin increased the single fruit weight, yield, fruit shape index and edible rate. It also improved pericarp L* value, a* value, C* and decreased ho, improving the peel colour; exogenous Hemin enhanced soluble solids content and phenolic compounds content and antioxidant enzyme activities in the pulp of dragon fruit. In addition, exogenous Hemin increased the content of chlorophyll content in dragon fruit stems. Differential metabolites determined by metabolomic assay also indicated that Hemin significantly increased the content of active substances such as selagin. Additionally, the Hemin treatment H2 also activated the activity of antioxidant enzymes such as superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX), which helps to mitigate the effects of high temperatures on dragon fruit. The current findings strongly advocate that H2 treatment may effectively counteract the adverse effects of heat stress by regulating the morph-physiological and antioxidant traits.

Casimir force densities, i.e., force per area, become very large if two solid material surfaces come closer together to each other than 10 nm. In most cases, the forces are attractive. In some cases, they can be repulsive depending on the solid materials and the fluid medium in between. This review provides an overview of experimental and theoretical studies that have been performed and focuses on four main aspects: (i) the combinations of different materials, (ii) the considered geometries, (iii) the applied experimental measurement methodologies and (iv) a novel self-assembly methodology based on Casimir forces. Briefly reviewed is also the influence of additional parameters such as temperature, conductivity, and surface roughness. The Casimir effect opens many application possibilities in microelectromechanical systems (MEMS) and nanoelectromechanical systems (NEMS), where an overview is also provided. The knowledge generation in this fascinating field requires interdisciplinary approaches to generate synergetic effects between technological fabrication metrology, theoretical simulations, the establishment of adequate models, artificial intelligence, and machine learning. Finally, multiple applications are addressed as a research roadmap.

Abstract Electronic health record (EHR) data is crucial in providing comprehensive historical disease information for patients and is frequently utilized in health event prediction. However, current deep learning models that rely on EHR data encounter significant challenges. These include inadequate exploration of higher‐order relationships among diseases, a failure to capture dynamic relationships in existing relationship‐based disease prediction models, and insufficient utilization of patient symptom information. To address these limitations, a novel dynamic HyperGraph‐based deep learning model is introduced for disease prediction (DHGL) in this study. Initially, pertinent symptom information is extracted from patients to assign them with an initial embedding. Subsequently, sub‐hypergraphs are constructed to consider distinct patient cohorts rather than treating them as isolated entities. Ultimately, these hypergraphs are dynamized to gain a more nuanced understanding of patient relationships. The evaluation of DHGL on real‐world EHR datasets reveals its superiority over several state‐of‐the‐art baseline methods in terms of predictive accuracy.

Here we report a rare morphology of a cardiac fibroma in a child. A 2-year and 8-month-old toddler came for “chronic constipation” and was found to have a heart murmur on cardiac auscultation. Further transthoracic echocardiography suggested “a strong echogenic mass in the left ventricular wall, with some part of “a string of beads” in shape extending into left ventricle outflow tract”, which was atypical for either a tumor, thrombus or vegetation. The child underwent resection of the mass and mitral valvuloplasty. Pathological examination confirmed the mass as a cardiac fibroma.

ObjectiveDistant metastasis occurs in some patients at the first diagnosis of nasopharyngeal carcinoma (NPC), the prognosis is poor, and there are significant individual differences. This study established a nomogram model of lung metastasis of NPC as a supplement to TNM staging.MethodsThe training cohort is used to build the nomogram model, and the validation cohort is used to evaluate the model. The training cohort of 177 patients is from the Surveillance, Epidemiology, and End Results (SEER) database. Factors affecting overall survival (OS) in patients with lung metastasis of NPC analysis by Cox regression analysis and then a nomogram were established. 122 patients from the Affiliated Tumor Hospital of Guangxi Medical University were selected as the external validation cohort. The concordance index (C-index), the area under the curve (AUC), and the calibration curve were used to assess the accuracy of the nomogram and used the decision curve analysis (DCA) curve to measure the clinical benefit capacity of the model. The patients were separated into two groups with different risks, and the “Kaplan-Meier (KM)” survival analysis was used to evaluate the differentiation ability of the model.ResultsAge, T-stage, radiation, chemotherapy, and brain metastases can affect the OS in NPC with lung metastasis. A nomogram was developed according to the above five factors. The C-index of the training cohort and the validation cohort were 0.726 (95% CI: 0.692-0.760) and 0.762 (95% CI: 0.733-0.791). The AUC of the nomogram was better than that of the TNM staging. In the training cohort, the nomogram predicted OS AUC values of 0.767, 0.746, and 0.750 at 1, 2, and 3 years, TNM stage of 0.574, 0.596, and 0.640. In the validation cohort, nomogram predictions of OS AUC values of 0.817, 0.857, and 0.791 for 1, 2, and 3 years, TNM stage of 0.575, 0.612, and 0.663. DCA curves suggest that nomogram have better clinical net benefits than TNM staging. The KM survival analysis shows that the nomogram has a reasonable risk stratification ability.ConclusionThis study successfully established a nomogram model of NPC lung metastasis, which can be used as a supplement to TNM staging and provide reference for clinicians.

In pipe jacking engineering, accurate prediction of jacking force is the key to pipe jacking design. Based on a project of the Beijing Daxing Airport Line, the influence of the advance jacked pipes on the jacking force of the subsequent pipe is carried out in the present work. First, the verified numerical model of practical engineering was established, and the jacking force and radial stress of different pipes were analyzed. Then, the two pipes were taken as research object, and the parameters of spacing, angle, buried depth, and pipe diameter were investigated, respectively. The results show that in the actual project, the advance jacked pipes have amplification and superposition effects on friction resistance of the subsequent pipe, and the maximum growth rate is 37.2%. The friction resistance of the subsequent pipe presents a trend of first increasing and then decreasing with the change of the layout angle of advance jacked pipe from 0° to 180°. With the increase of buried depth and pipe diameter, the absolute value of incremental friction resistance of the subsequent pipe increases gradually, but the growth rate remains constant. Finally, the empirical formulas for predicting the friction resistance growth rate of subsequent pipes under different angles are proposed. The research results can provide some reference for the design of pipe jacking.

Rice aroma, one of the most important qualities of rice, was the comprehensive result of volatiles in rice and human sense. In this study, the main volatile compounds in rice were analyzed by using gas chromatography-mass spectrometry and gas chromatography-olfactometry, and their correlations with sensory score were investigated. A total of eighty-five volatiles were found in rice samples. By combining odor activity value and correlation analysis, nine volatiles were considered as potential characteristic volatiles in rice aroma, namely hexanal, 2-pentylfuran, octanal, 2-acetyl-1-pyrroline (2-AP), 1-octen-3-ol, trans-2-octenal, decanal, trans-2-nonenal and trans, trans-2,4-decadienal. It was found that the volatiles negatively correlated with sensory scores were positively correlated with hexanal. It indicated that hexanal might be a representative of the negative volatiles of rice aroma. The effects of the nine potential characteristic volatiles on rice aroma were investigated by using sensory analysis. The results showed that the odor intensity and preference level of 2-AP, hexanal, and 1-octen-3-ol were significantly affected by the content. Furthermore, the aroma of cooked rice was significantly different after adding 2-AP, hexanal or trans, trans-2,4-decadienal. Rice aroma was increased by adding 2-AP and deteriorated by adding hexanal or trans, trans-2,4-decadienal, indicating that 2-AP contributed positively to rice aroma while hexanal and trans, trans-2,4-decadienal contributed negatively to rice aroma. Hexanal, 2-AP, and trans, trans-2,4-decadienal were suggested to be the key characteristic volatiles for future aroma evaluation.

Existing healthcare data-sharing solutions often combine attribute-based encryption techniques with blockchain technology to achieve fine-grained access control. However, the transparency of blockchain technology may introduce potential risks of exposing access structures and user attributes. To address these concerns, this paper proposes a novel healthcare data-sharing scheme called HA-Med. By leveraging blockchain technology, HA-Med ensures the concealment of access policies and attributes, providing a secure solution for fine-grained access control of medical data. Furthermore, the scheme supports attribute revocation and forward secrecy to enhance user privacy. The security of HA-Med is rigorously verified through theoretical analysis, and its feasibility is demonstrated through experiments conducted using the Java-based JPBC library.

Background: This study aimed to assess the overall reporting quality of randomized controlled trials (RCTs) in Chinese herbal medicine (CHM) formulas for patients with diabetes, and to identify factors associated with better reporting quality.Methods: Four databases including PubMed, Embase, Cochrane Library and Web of Science were systematically searched from their inception to December 2022. The reporting quality was assessed based on the Consolidated Standards of Reporting Trials (CONSORT) statement and its CHM formula extension. The overall CONSORT and its CHM formula extension scores were calculated and expressed as proportions separately. We also analyzed the pre-specified study characteristics and performed exploratory regressions to determine their associations with the reporting quality.Results: Seventy-two RCTs were included. Overall reporting quality (mean adherence) were 53.56% and 45.71% on the CONSORT statement and its CHM formula extension, respectively. The strongest associations with reporting quality based on the CONSORT statement were multiple centers and larger author numbers. Compliance with the CHM formula extension, particularly regarding the disclosure of the targeted traditional Chinese medicine (TCM) pattern (s), was generally insufficient.Conclusion: The reporting quality of RCTs in CHM formulas for diabetes remains unsatisfactory, and the adherence to the CHM formula extension is even poorer. In order to ensure transparent and standardized reporting of RCTs, it is essential to advocate for or even mandate adherence of the CONSORT statement and its CHM formula extension when reporting trials in CHM formulas for diabetes by both authors and editors.

Understanding how climate change has been affecting crop yield is a prerequisite to inform adaptation decisions and to ensure global food security. The Northeast China (NEC), located in high-latitude area, is significantly affected by climate change. There is a high demand for quantitative information on impacts of climate variability on crop yields in NEC. In this study, we applied panel regression models to explore the yield-climate relationship and its spatial variations based on experimentally observed yield (Ys) and the county-scale statistical yield (Yc) of three typical crops (e.g., maize, rice and soybean) across NEC from 1981 to 2010, as well as contemporary climate data. The results indicated that Ys (Yc) of maize, rice and soybean during the past three decades increased by 64.2% (82.0%), 47.5% (55.3%), and 59.2% (58.0%), respectively. Moreover, we found climate during crop growth period had changed significantly and the change had caused measurable impacts on crop yields. Changes in temperature, precipitation and solar radiation jointly decreased Ys (Yc) of maize and soybean by 1.3% (0.7%) and 0.3% (1.1%), respectively, however increased Ys (Yc) of rice by 1.2% (2.2%), with a large spatial difference. Therefore, the impact of climate change on yields of three crops was far less than the actual increase in crop yields. Our finding suggest that other factors, mainly improved management practices, may be the main reason for the significant increase in crop yields in NEC over the past few decades. Although historical climate change also played an important role in the yields of three crops, certain improvement in management measures not only compensated for the negative impact of climate change, but also greatly promoted the increase in crop yields. Therefore, in proposing strategies for crop production to cope with climate change, we need in-depth assessments of the role of improved management.

Abstract The coexistence of electric dipoles and itinerant electrons in a solid was postulated decades ago, before being experimentally established in several ‘polar metals’ during the last decade. Here, we report a concentration-driven polar-to-nonpolar phase transition in electron-doped BaTiO3. Comparing our case with other polar metals, we find a particular threshold concentration (n *) linked to the dipole density (n d). The universal ratio $$\frac{{n}_{{{{\rm{d}}}}}}{{n}^{* }}\approx 8.0(6)$$ n d n * ≈ 8.0 ( 6 ) suggests a common mechanism across different polar systems, possibly explained by a dipolar Ruderman-Kittel-Kasuya-Yosida theory. Moreover, in BaTiO3, we observe enhanced thermopower and upturn on resistivity at low temperatures near n *, resembling the Kondo effect. We argue that local electric dipoles act as two-level-systems, whose fluctuations couple with surrounding electron clouds, giving rise to a potential dipolar-counterpart of the Kondo effect. Our findings unveil a mostly uncharted territory for exploring emerging physics associated with electron-dipole correlations, encouraging further theoretical work on dipolar-RKKY and Kondo interactions.

Abstract Background We assessed health-related quality of life (HRQOL) and its determinants among rural glaucoma participants compared to age-matched normal controls in the population-based Handan Eye Study (HES), in rural Yongnian County, northern China. Methods We enrolled 99 adults with glaucoma (mean age 63.0 ± 11.0 years), including primary open-angle glaucoma (POAG, n = 67) and primary angle-closure glaucoma (PACG, n = 32) and 102 controls (mean age 58.5 ± 5.3 years) with normal visual acuity and visual field and no history of glaucoma. Results of ophthalmic examinations and socioeconomic data were recorded. HRQOL was measured using the EQ-5D (converted to utility valves, UVs), and visual function (VF) and vision-related quality of life (VRQOL) were evaluated using the visual function-quality of life (VF-QOL) instrument. Primary and secondary outcome measures EQ-5D and VF-QOL scores. Results The mean UVs, VF, and VRQOL scores for glaucoma cases were 0.98 ± 0.04, 87.9 ± 15.2, and 95.5 ± 12.8, respectively, significantly worse than VF (94.4 ± 4.4) and VRQOL (100.0 ± 0.0) among controls, even after adjusting for age, gender, educational level, and family income (P = 0.015, P = 0.033). UVs were significantly lower among glaucoma participants with impaired VRQOL (55.4 ± 11.5) compared to those with normal VRQOL scores (99.1 ± 2.8) (UVs: 0.92 ± 0.08 vs. 0.99 ± 0.03, P = 0.036), also after adjustment for age and family income (P = 0.006). Participants with PACG had significantly lower VF and VRQOL scores compared to POAG (77.8 ± 21.4 vs. 92.9 ± 6.8, P

【Objective】Barthea barthei (Hance ex Benth.) Krass. is a unique shrub of the genus Barthea in Melastomataceae in China, which has important ornamental value. However, it is mainly distributed in the wild, and its artificial cultivation technology system has not been fully established, which greatly limits its application potential as a landscape plant. In this study, by comparing the effects of different types in nutrients and different application concentrations on the growth and root indexes of the seedlings, the main nutrient dosage affecting the growth of the seedlings was determined, providing a scientific basis for the cultivation of the seedlings.【Method】The tissue culture seedlings of B. barthei were used as materials, and they were transplanted into the seedling cups with yellow soil as the cultivation substrate. After 3 months' culture, 6 kinds of N nutrients (Glutamic acid, Alanine, Aspartic acid, Compound fertilizer, Urea, Controlled-released fertilizer) and 3 kinds of application amount (0.7, 1.4 and 2.8 mg/plant) were applied respectively. The seedling height and chlorophyll content of B. barthei were measured monthly, and the root indexes of B. barthei was measured after the experiment.【Result】Nutrient type and application amount had significant effects on the early growth and development of B. barthei seedlings. The highest increment of seedling height was 5.18±0.13 cm after 1 month of treatment with T9 (Aspartic acid, 2.8 mg/plant). The increment became smaller after 4~5 months. The seedling height increment of seedlings treated with T5 (Alanine, 1.4 mg/plant) was not significantly different from that of the control in the first 2 months, but it was much higher than that of the control after the 4th and 5th months. The increment of seedling height of T18 (Controlled-released fertilizer, 2.8 mg/plant) was the largest after 4 and 5 months. The root biomass of T14 (Urea, 1.4 mg/plant), T9 (Aspartic acid, 2.8 mg/plant) and T15 (Urea, 2.8 mg/plant) were the largest, which were 0.71 (±0.40) g, 0.65 (±0.21) g and 0.64 (±0.24) g, respectively. The root surface area with diameter less than or equal to 2 mm under T9 treatment was 273.63 cm2, which was significantly higher than that under other treatments.【Conclusion】Considering the seedling height and root index of root surface area with diameter ≤ 2 mm, the best nutrient for the early stage of B. barthei growth was Aspartic acid with the amount of 2.8 mg/plant.

Abstract Background Epithelial ovarian cancer is the leading cause of death from gynecologic cancer, in which serous ovarian carcinoma (SOC) is the most common histological subtype. Although PARP inhibitors (PARPi) and antiangiogenics have been accepted as maintenance treatment in SOC, response to immunotherapy of SOC patients is limited. Methods The source of transcriptomic data of SOC was from the Cancer Genome Atlas database and Gene Expression Omnibus. The abundance scores of mesenchymal stem cells (MSC scores) were estimated for each sample by xCell. Weighted correlation network analysis is correlated the significant genes with MSC scores. Based on prognostic risk model construction with Cox regression analysis, patients with SOC were divided into low- and high-risk groups. And distribution of immune cells, immunosuppressors and pro-angiogenic factors in different risk groups was achieved by single-sample gene set enrichment analysis. The risk model of MSC scores was further validated in datasets of immune checkpoint blockade and antiangiogenic therapy. In the experiment, the mRNA expression of prognostic genes related to MSC scores was detected by real-time polymerase chain reaction, while the protein level was evaluated by immunohistochemistry. Results Three prognostic genes (PER1, AKAP12 and MMP17) were the constituents of risk model. Patients classified as high-risk exhibited worse prognosis, presented with an immunosuppressive phenotype, and demonstrated high micro-vessel density. Additionally, these patients were insensitive to immunotherapy and would achieve a longer overall survival with antiangiogenesis treatment. The validation experiments showed that the mRNA of PER1, AKAP12, and MMP17 was highly expressed in normal ovarian epithelial cells compared to SOC cell lines and there was a positive correlation between protein levels of PER1, AKAP12 and MMP17 and metastasis in human ovarian serous tumors. Conclusion This prognostic model established on MSC scores can predict prognosis of patients and provide the guidance for patients receiving immunotherapy and molecular targeted therapy. Because the number of prognostic genes was fewer than other signatures of SOC, it will be easily accessible on clinic.

Efforts have been made to improve the therapeutic efficiency of tumor treatments, and metal-organic frameworks (MOFs) have shown excellent potential in tumor therapy. Monotherapy for the treatment of tumors has limited effects due to the limitation of response conditions and inevitable multidrug resistance, which seriously affect the clinical therapeutic effect. In this study, we chose to construct a multiple cascade synergistic tumor drug delivery system MIL−101(Fe)−DOX−TCPP−MnO2@PDA−Ag (MDTM@P−Ag) using MOFs as drug carriers. Under near-infrared (NIR) laser irradiation, 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) and Ag NPs loaded on MDTM@P−Ag can be activated to generate cytotoxic reactive oxygen species (ROS) and achieve photothermal conversion, thus effectively inducing the apoptosis of tumor cells and achieving a combined photodynamic/photothermal therapy. Once released at the tumor site, manganese dioxide (MnO2) can catalyze the decomposition of hydrogen peroxide (H2O2) in the acidic microenvironment of the tumor to generate oxygen (O2) and alleviate the hypoxic environment of the tumor. Fe3+/Mn2+ will mediate a Fenton/Fenton-like reaction to generate cytotoxic hydroxyl radicals (·OH), while depleting the high concentration of glutathione (GSH) in the tumor, thus enhancing the chemodynamic therapeutic effect. The successful preparation of the tumor drug delivery system and its good synergistic chemodynamic/photodynamic/photothermal therapeutic effect in tumor treatment can be demonstrated by the experimental results of material characterization, performance testing and in vitro experiments.

Conventional microfluidic systems that rely on capillary force have a fixed structure and limited sensitivity, which cannot meet the demands of clinical applications. Herein, we propose a dual-drive microfluidic device for sensitive and flexible detection of multiple pathogenic microorganisms antigens/antibodies. The device comprises a portable microfluidic analyzer and a dual-drive microfluidic chip. Along with capillary force, a second active driving force is provided by a removable self-driving valve in the waste chamber. The interval between these two driving forces can be adjusted to control the reaction time in the microchannel, optimizing the formation of antigen-antibody complexes and enhancing sensitivity. Moreover, the material used in the self-driving valve can be changed to adjust the active force strength needed for different tests. The device offers quantitative analysis for respiratory syncytial virus antigen and SARS-CoV-2 antigen using a 35 μL sample, delivering results within 5 min. The detection limits of the system were 1.121 ng/mL and 0.447 ng/mL for respiratory syncytial virus recombinant fusion protein and SARS-CoV-2 recombinant nucleoprotein, respectively. Although the dual-drive microfluidic device has been used for immunoassay for respiratory syncytial virus and SARS-CoV-2 in this study, it can be easily adapted to other immunoassay applications by changing the critical reagents.

IntroductionThis study aimed to investigated the effects of 10-hydroxy-2-decenoic acid (10-HDA) on the growth performance, intestinal barrier, inflammatory response, oxidative stress, and gut microbiota of chickens challenged with lipopolysaccharide (LPS).MethodsA total of 240 one-day-old chickens were randomly assigned to five treatment groups: (1) control group (basal diet + saline); (2) LPS group (basal diet + LPS); (3) Chlortetracycline (CTC) group (basal diet containing 75 mg/kg CTC + LPS); (4) 0.1% 10-HDA group (basal diet containing 1 g/kg 10-HDA + LPS); and (5) 0.5% 10-HDA group (basal diet containing 5 g/kg 10-HDA + LPS). All chickens were injected intraperitoneally with 0.5 mg/kg body weight of either LPS or saline at 17, 19, and 21 days of age.ResultsThe results showed that dietary 10-HDA supplementation attenuated the loss in growth performance caused by the LPS challenge (p

The growth and metastasis of malignant solid tumors depend closely on new blood vessels. Vasculogenic mimicry provides a special pathway of blood supply during the early growth of malignant tumors, and real-time monitoring of its occurrence and development in vivo is important to clinical applications. However, there are few labels with sufficient brightness and stability in vivo to achieve high spatiotemporal resolution imaging of deep tissue for noninvasive optical detection of vasculogenic mimicry in tumor tissues. In this study, we constructed a high-brightness fluorescent label with fluorescence in the near-infrared-II region, which can be used not only for in vivo tumor imaging but also for tissue section imaging. Real-time high-resolution imaging of tumor vessels has been achieved with PbS quantum dots (QDs) surface-coupled with horseradish peroxidase (HRP) (HRP-QDs) by taking advantage of the low background autofluorescence of tissue at the near-infrared-II wavelength for in vivo and tissue section imaging. Qualitative and quantitative analysis of early blood supply patterns of tumor growth enables monitoring neovascularization to accurate noninvasive identification of benign and malignant solid tumors.

Abstract Various deep learning‐based video frame interpolation methods have been proposed in the past few years, but how to generate high quality interpolated frames in videos with large motions, complex backgrounds and rich textures is still a challenging issue. To deal with this limitation, a frame interpolation method based on residual blocks and feature pyramids is proposed. U‐Net is the main architecture of our method, which can capture multi‐layer information, segment objects from the background and obtain parameters with motion information to guide frame interpolation. However, the upsampling and subsampled of U‐Net will lose important information. In order to acquire more detailed contextual information, shortcut connection is used in the encoder basic module. At the same time, feature pyramid network is employed to capture features at different scales of the decoder to improve the representation of inter‐frame spatial‐temporal features. The experimental results show that the proposed method outperform the baseline methods in both of objective and subjective evaluations on different datasets. In particular, the method has obvious advantages on datasets which contain complex background.

Effects of Al and La elements on mechanical properties of CoNiFe0.6Cr0.6 high-entropy alloys (HEAs) with face-centered cubic (FCC) structure were investigated by first-principles calculations. The variation curves of relevant physical parameters, including lattice constants, formation enthalpy, elastic constants, elastic modulus, Poisson's ratio, Pugh's ratio, Cauchy pressure, anisotropy factors, Vickers hardness, yield strength, and energy factor, as a function of Al and La concentration were discussed in detail. Results show that the resistances to bulk, elastic, and shear deformation decrease with the increase of Al and La concentration. The addition of Al and La can improve the plasticity and ductility of HEAs. Meanwhile, with the increase of Al and La concentration, the metallic characteristic of atomic bonding strengthens and the anisotropy of materials increases. Moreover, the energy factor indicates that the addition of Al and La could promote dislocation nucleation. This study provides a guideline for further research on non-equiatomic CrFeCoNi series HEAs with designed mechanical properties.

Objective: Polyploid giant cancer cells (PGCCs) with daughter cells express epithelial–mesenchymal transition (EMT)-associated proteins. Highly malignant tumor cells with EMT properties can transdifferentiate into mature tumor cells. In this study, we elucidated the potential for, and underlying mechanism of, adipogenic differentiation of PGCCs with daughter cells (PDCs). Methods: Cobalt chloride was used to induce PGCC formation in HEY (wild-type P53) and MDA-MB-231 (mutant P53) cells; these cells were then cultured in adipogenic differentiation medium. Oil red O staining was used to confirm adipogenic differentiation, and the cell cycle was detected with flow cytometry. The expression of adipogenic differentiation-associated proteins and P300 histone acetyltransferase activity were compared before and after adipogenic differentiation. Animal xenograft models were used to confirm the adipogenic differentiation of PDCs. Results: PDCs transdifferentiated into functional adipocytes. Two different cell cycle distributions were observed in PDCs after adipogenic differentiation. The expression levels of PPARγ, Ace-PPARγ, and Ace-P53 were higher in PDCs after adipogenic differentiation than in cells before adipogenic differentiation. Ace-PPARγ and FABP4 expression increased in HEY cells and decreased in MDA-MB-231 PDCs after p53 knockdown. A485 treatment increased Ace-P53, Ace-PPARγ, and FABP4 expression in HEY PDCs by inhibiting SUMOylation of P53. In MDA-MB-231 PDCs, A485 treatment decreased Ace-P53, Ace-PPARγ, and FABP4 expression. Animal experiments also confirmed the adipogenic differentiation of PDCs. Conclusions: Acetylation of P53 and PPARγ plays an important role in the adipogenic differentiation of PDCs.

Abstract Gap junctions (GJs), which are composed of connexins (Cxs), provide channels for direct information exchange between cells. Cx expression has a strong spatial specificity; however, its influence on cell behavior and information exchange between cells cannot be ignored. A variety of factors in organisms can modulate Cxs and subsequently trigger a series of responses that have important effects on cellular behavior. The expression and function of Cxs and the number and function of GJs are in dynamic change. Cxs have been characterized as tumor suppressors in the past, but recent studies have highlighted the critical roles of Cxs and GJs in cancer pathogenesis. The complex mechanism underlying Cx and GJ involvement in cancer development is a major obstacle to the evolution of therapy targeting Cxs. In this paper, we review the post-translational modifications of Cxs, the interactions of Cxs with several chaperone proteins, and the effects of Cxs and GJs on cancer. Video Abstract

The starch synthase (SS) plays important roles in regulating plant growth and development and responding to adversity stresses. Although the SS family has been studied in many crops, it has not been fully identified in sweet potato and its two related species. In the present study, eight SSs were identified from Ipomoea batatas (I. batata), Ipomoea trifida (I. trifida), and Ipomoea trlioba (I. trlioba), respectively. According to the phylogenetic relationships, they were divided into five subgroups. The protein properties, chromosomal location, phylogenetic relationships, gene structure, cis-elements in the promoter, and interaction network of these proteins were also analyzed; stress expression patterns were systematically analyzed; and real-time polymerase chain reaction (qRT-PCR) analysis was performed. Ipomoea batatas starch synthase (IbSSs) were highly expressed in tuber roots, especially Ipomoea batatas starch synthase 1 (IbSS1) and Ipomoea batatas starch synthase 6 (IbSS6), which may play an important role in root development and starch biosynthesis. At the same time, the SS genes respond to potassium deficiency, hormones, cold, heat, salt, and drought stress. This study offers fresh perspectives for enhancing knowledge about the roles of SSs and potential genes to enhance productivity, starch levels, and resistance to environmental stresses in sweet potatoes.

p21-Activated kinase 4 (PAK4), one of the serine/threonine kinases activated by Rho-family GTPases, has been widely studied as an oncogenic protein that is overexpressed in many types of cancers. In our recent study, PAK4 upregulation was observed in mice exhibiting hepatic ischaemia-reperfusion (I/R) and in liver transplantation patients. Liver I/R injury was also attenuated in Pak4 KO mice. Herein, we report a novel series of pyrazolo[3,4-d]pyrimidine derivatives of type I ½ PAK4 inhibitors. The most potent compound SPA7012 was evaluated to determine the pharmacological potential of PAK4 inhibitor in I/R injury in mice. Mice with I/R injury showed typical patterns of liver damage, as demonstrated by increases in serum levels of aminotransferases and proinflammatory cytokines, hepatocellular necrosis and apoptosis, and inflammatory cell infiltration, relative to sham mice. Conversely, intraperitoneal administration of SPA7012 dramatically attenuated biochemical and histopathologic changes. Mechanistically, stabilisation of nuclear factor-erythroid 2-related factor 2 (Nrf2), a master regulator of anti-oxidative response, was observed following SPA7012 treatment. SPA7012 treatment in primary hepatocytes also attenuated hypoxia-reoxygenation-induced apoptotic cell death and inflammation. Together, these results provide experimental evidence supporting the use of PAK4 inhibitors for alleviation of I/R-induced liver damage.

Abstract Background Hydrogen peroxide (H2O2) is the commonly used bleaching agent for teeth. But it is highly corrosive to teeth for the high concentration. The cold atmospheric pressure plasma has been witnessed a novel tooth bleaching technology and could help strengthen the bleaching effect when combined with H2O2. However, the efficacy and safety might highly correlated with processing time. The present study aims to evaluate the time-dependent efficacy and safety of tooth bleaching with cold plasma and H2O2 gel in vitro. Methods The H2O2 concentrations of the gel used in the study are 6%, 15%, 25% and 35%, respectively and the treatment time varies from 5 to 20 min. The tooth bleaching effect was evaluated by a Crystaleye Spectrophotometer and the overall change of the colorimetric value based on three independent measurements. Meanwhile, the microhardness, roughness and tooth temperature were evaluated. The surface morphology and the elemental composition were determined by scanning electron microscope and energy-dispersive X-ray spectroscopy. Results 5 min bleaching treatment contributed to 60% of the bleaching effect maximum, the 10 min effect was close to 15 min effect. Meanwhile, the microhardness reduced and roughness increased under a treatment which was longer than 20 min. Tooth pulp chamber temperature was keeping in a safe range within 20 min treatment. Conclusion 5–10 min was the best treatment time from which we can get an ideal tooth bleaching effect and less influence on tooth enamel and pulp tissue when using cold plasma and H2O2 gel.

Abstract Background Atrial septal defect is one of the most common types of congenital heart disease. This study aims to explore the surgical and cosmetic effects of open-heart surgery with right vertical axillary incision for simple congenital heart disease in infants. Methods From June 2018 to October 2021, children who underwent direct surgery of atrial septal defect in our department were selected for a propensity score matched study. Those with direct surgery through the right vertical axillary incision were included in the right vertical axillary incision group. According to age and weight, propensity score matching method was employed to match children from the right vertical axillary incision group with those undergoing direct surgery through median sternotomy (median sternotomy group) at a 1:2 ratio. Surgery outcomes between two groups were compared to evaluate the effectiveness and safety of right vertical axillary incision group. Results The median incision length (median, [interquartile range]) in right vertical axillary incision group (4.8 cm, [4.0–5.0]) was shorter than that in median sternotomy group (p