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Abstract Background This study aims to explore the effects of the iris-ciliary angle (ICA) on the accurate prediction of the vault after implantable collamer lens (ICL) using the manufacturer’s online calculation and ordering system (OCOS). Methods The participants were categorized into three groups according to the size of ICA as follows: narrow ICA group ( 60°). We compared the preoperative ocular characteristics and postoperative vault at 3 months among the three groups. Bivariate correlation was used to analyze the correlation between vault and ICA, and multiple linear regression was used to further analyze the correlation between vault and preoperative parameters. Ordered multicategorical logistic regression analyses were used to further illustrate the effect of different ICA groups on postoperative vault distribution. Results This study included 278 eyes of 157 individuals. There were no statistically significant differences in preoperative ocular parameters among the three ICA groups, while the postoperative vault was minimal in the wide ICA group, followed by the normal and then the narrow ICA group (p

Objective Recently, the application in the field of germplasm resource conservation has become an important application of primordial germ cells (PGCs). However, due to the lack of deep understanding of the biological characteristics of PGCs at different time points, there is no systematic scheme for the selection of PGCs at which time points in practical application, which affects the practical application effect of PGCs. This study aims to clarify the differences in PGCs during development. Methods Here, migration experiment, EdU proliferation assay and cell apoptosis assay were conducted to compare the differences in the migration ability, the proliferation ability and the recovery efficiency among female and male PGCs at E3.5, E4.5, and E5.5, which were explained by the following transcriptome sequencing analysis. Results We found that there were larger differences between female and male PGCs at different embryonic ages, while smaller differences between female and male PGCs at the same embryonic age. Further comparison showed that the cell migration ability of female and male PGCs decreased gradually during development, so female and male PGCs at E3.5 are more suitable for in vitro allotransplantation. At the same time, the proliferation ability of PGCs gradually decreased during development, and cell adhesion and extracellular matrix communication were weakened, indicating that female and male PGCs of E3.5 are more suitable for in vitro long-term culture cell line establishment. Interestingly, female and male PGCs at E5.5 showed strong DNA damage repair ability, thus more suitable for in vitro long-term cryopreservation. Conclusion This study provides a theoretical basis for systematically selecting PGCs at suitable developmental time points as cell materials for efficient utilization by analyzing the characteristics of female and male PGCs at different developmental time points based on transcriptome.

Abstract Objectives Chicken (Gallus gallus), as the most economically important poultry, is a classical and ideal model for studying the mechanism of vertebrate developmental biology and embryology. However, the sex determination and differentiation in chicken is still elusive, which limited the application and slowed down many basic studies in chicken. Data description We applied PacBio Iso-seq to multiple spatiotemporal embryo-gonad tissues in the male and female chicken, which contain the blastoderm (E0, un-differentiation stage), genital ridge (E3.5–6.5, sex-differentiation stage) and gonads (E18.5, full-sex-differentiation stage). We obtained 51,479 and 48,356 full-length transcripts in male and female chicken embryo, respectively. The comprehensive annotated and evaluated these transcripts. The 1,293 and 1,556 candidate lncRNAs, 5,766 and 4,211 AS events in male and female. Collectively, our data constitutes a grand increase in the known number of lncRNA, AS (Alternative splicing) and Poly(A) during chicken embryo sex-differentiation and plays an important role in improving current genome annotation. In the meantime, the data will be enriched the functional studies in other birds.

This study investigates the role of histone acetylation in the differentiation of chicken embryonic stem cells (ESCs) into primordial germ cells (PGCs). Transcriptomic sequencing was used to analyze differentially expressed genes during this differentiation process, with functional annotation identifying genes associated with histone acetylation. To explore the role of acetylation, acetate and an acetyltransferase inhibitor (ANAC) were added to the ESCs induction medium. Transcriptomic analysis revealed that during ESCs differentiation into PGCs, genes involved in histone acetyltransferase activity were upregulated, while those associated with histone deacetylase activity were downregulated. Functional enrichment analysis indicated these genes are involved in pathways critical for germ cell differentiation, underscoring their importance in avian reproductive biology. Quantitative real-time PCR (qRT-PCR) confirmed significant differential expression of HAT8 and HDAC10 between ESCs and PGCs (P < 0.01). The acetate treatment group exhibited a significantly higher number of embryoid bodies and elevated expression levels of CVH, C-KIT, and NANOS3 compared to the ANAC group (P < 0.01). Furthermore, indirect immunofluorescence and flow cytometry demonstrated a significantly higher proportion of DDX4-positive cells in the acetate group (P < 0.01). These findings provide preliminary evidence that histone acetylation regulates chicken PGCs formation, offering a theoretical framework for the epigenetic induction of PGCs in vitro. This study enhances our understanding of the molecular mechanisms underlying PGCs development in poultry and contributes to advancements in avian reproductive technologies and genetic conservation.

Abstract Background To assess the relationship between postoperative implantable collamer lens (ICL) vault and lens height obtained from two different measurements. Methods A retrospective case series study enrolled eyes with horizontally implanted ICL. Crystal lens rise (CLR) and the distance between STS plane and anterior crystalline lens surface (STSL) were measured in the horizontal and vertical directions using ultrasound biomicroscopy (UBM). We compared the differences in the parameters measured in both horizontal and vertical directions. The participants were categorized into three groups according to ciliary sulcus width (CSW) which is defined as the distance between the posterior angle of the iris and the anterior angle of the ciliary process: narrow CSW group (NSG); medium CSW group (MSG); and wide CSW group (WSG). The correlations between CLR/STSL and vault were examined in each of the three groups. Biased correlation analysis was used further to contrast the correlation between CLR/STSL and vault. Results This retrospective study included 223 myopic eyes. Vertical STSL (VSTSL) and vertical CLR (VCLR) exhibited significantly greater values compared to their horizontal counterparts (both P

Abstract Aerosol jet printing has the potential to fabricate fine features on various substrates due to its large stand-off distance. However, the presence of overspray and instability, particularly at high printing resolutions, has limited its widespread application. In this study, we introduce an efficient approach called annular acoustic focusing for aerosol jet printing. By determining the optimal focusing frequency (5.8 MHz) for silver nanoparticles using a particle ejection model, we achieve precise and stable printing. We also propose a modified print nozzle geometry, resulting in ultrafine traces (line width

ABSTRACT: Avian primordial germ cells (PGCs) are important culture cells for the production of transgenic chickens and preservation of the genetic resources of endangered species; however, culturing these cells in vitro proves challenging. Although the proliferation of chicken PGCs is dependent on insulin, the underlying molecular mechanisms remain unclear. In the present study, we explored the expression of the PI3K/AKT signaling pathway in PGCs, investigated its effects on PGC self-renewal and biological properties, and identified the underlying mechanisms. Our findings indicated that although supplementation with the PI3K/AKT activator IGF-1 failed to promote proliferation under the assessed culture conditions, the PI3K/AKT inhibitor LY294002 resulted in retarded cell proliferation and reduced expression of germ cell-related markers. We further demonstrated that inhibition of PI3K/AKT regulates the cell cycle and promotes apoptosis in PGCs by activating the expression of BAX and inhibiting that of Bcl-2. These findings indicated that the PI3K/AKT pathway is required for cell renewal, apoptosis, and maintenance of the reproductive potential in chicken PGCs. This study aimed to provide a theoretical basis for the optimization and improvement of a culture system for chicken PGCs and provide insights into the self-renewal of vertebrate PGCs as well as potential evolutionary changes in this unique cell population.

Planting concrete (PC) is a type of sustainable concrete. It remains challenging to prepare and design a PC by considering complex factors such as voidage and alkalinity. In this paper, preparation and mix design methods of PC are reviewed and compared, with particular emphasis on the influence of various factors on permeability, mechanical properties, durability, and plant compatibility. Alkali reduction measures, vegetation testing, and plant compatibility cannot be ignored in the design of PC. 25∼30% voidage and 8–10 pH can ensure the durability of vegetation concrete, physiological characteristics of plants and fertilizer retention performance. In addition, the paper summarizes the application of PC in water purification, slope protection and green roof establishment. The cost and applicable conditions of different slope protection methods are further compared and analyzed. Finally, several essential areas that require further research efforts are suggested based on the current research results, including research direction and challenges of PC.

Traffic accidents frequently lead to fatal injuries, claiming millions of lives every year. To mitigate driving hazards and ensure personal safety, it is crucial to assist vehicles in anticipating the objects in the traffic scene (treated here as important objects) which may pose a threat during the driving task. Previous research on important object detection primarily assessed the importance of individual participants, treating them as independent entities and frequently neglecting the interconnections among these participants. Unfortunately, this approach has proven less effective in detecting important objects in complex scenarios. In this work, we introduce Driving scene Relationship Understanding transformer (DRUformer), designed to enhance the important object detection task. The DRUformer is a transformer-based multi-modal important object detection model that takes into account the relationships between all the participants in the driving scenario. Recognizing that driving intention also significantly affects the detection of important objects during driving, we have incorporated a module for embedding driving intention. To assess the performance of our approach, we conducted comparative experiments on the DRAMA dataset, comparing our model against other state-of-the-art (SOTA) models. The results demonstrated a noteworthy 16.2% improvement in mIoU and a substantial 12.3% boost in ACC compared to SOTA methods. Furthermore, we conducted a qualitative analysis of our model’s ability to detect important objects across different road scenarios and classes, highlighting its effectiveness in diverse contexts. Finally, we conducted various ablation studies to assess the efficiency of the proposed modules in our DRUformer model. Through extensive experimentation, it has been demonstrated that our model performs exceptionally well in the task of driving scene important object localization. The code is publicly available on the following link: https://github.com/oniu-uin0/DRUformer

The only cells in an organism that could do any other sort of cell until 2006 (except sperm or egg) were known as embryonic stem cells, ESC [...]

The accurate prediction of vehicle behavior is crucial for autonomous driving systems, impacting their safety and efficiency in complex urban environments. To address the challenge of multi-agent trajectory prediction, we propose a novel model integrating multiple input modalities, including historical trajectories, map data, vehicle features, and interaction information. Our approach employs a Conditional Variational Autoencoder (CVAE) framework with a decoder that predicts control actions using the Gaussian Mixture Model (GMM) and then converts these actions into dynamically feasible trajectories through a bicycle model. Evaluated on the nuScenes dataset, the model achieves great performance across key metrics, including minADE5 of 1.26 and minFDE5 of 2.85, demonstrating robust performance across various vehicle types and prediction horizons. These results indicate that integrating multiple data sources, physical models, and probabilistic methods significantly improves trajectory prediction accuracy and reliability for autonomous driving. Our approach generates diverse yet realistic predictions, capturing the multimodal nature of future outcomes while adhering to Physical Constraints and vehicle dynamics.

Background: Educating and training clinicians to deliver nutrition interventions is critical to improve population health. However, the adequacy of nutrition education within primary care adult and family nurse practitioner (ANP/FNP) curricula has not been addressed. Purpose: The purpose of this study was to describe faculty perceptions of nutrition education in ANP/FNP programs. Methods : We used a cross-sectional design to gather data on nutrition education. The survey was administered to a convenience sample of faculty from the United States. Results : Our response rate was 47.8% (N = 49). The mean +/- SD hours of nutrition education was 14.4 +/- 14.6. One-fourth of schools reported that their students received at least 25 hours of nutrition education. Most participants thought it was very or extremely important (75.6%) that their students become more educated about nutrition. Conclusions : There is a need and desire for more nutrition education within nursing graduate curricula. Novel strategies to implement nutrition education in nurse practitioner curriculum are needed. [ABSTRACT FROM AUTHOR]

Three-dimensional (3D) conformal printing of temperature sensors with a wide sensing range and high stability requires the potential printable material with excellent functionality and printability. Herein, a high-performance silver nanoparticles (Ag NPs) decorated reduced graphene oxide (RGO)/Ag (ADR/Ag) ink with low viscosity was synthesized for aerosol jet printing (AJP). Ag ions are electrostatically adsorbed on the graphene oxide (GO) surface, and Ag NPs (∼10 nm) were attached onto the RGO surface by in-situ liquid-phase reduction. The ADR nanoflakes were mixed with commercial Ag NPs ink, high resolution patterns with ink stream widths down to 10 μm are printed, and ADR/Ag-0.8% ink shows excellent low-temperature sintering capability and flexibility, and the resistivity of the printed traces is 9.79 × 10−5 Ω m after 1 h sintering at a relatively low temperature (75 °C). The resistance negligibly increases by only 5% after 1000 bending cycles, which is about 7 times lower compared to the pure Ag traces. Furthermore, we achieve the 3D printing of a conformal temperature sensor with a sensitivity range of (1.162–1.519) × 10−3/°C in the broad sensing range of 0–200 °C. These findings shed light on the additive manufacturing of high-performance conformal electronics using the emerging AJP technology.

Abstract Background Early metastasis is a hallmark of osteosarcoma (OS), a highly common type of malignant tumor. Members of the potassium inwardly rectifying channel family exert oncogenic effects in various cancers. However, the role of the potassium inwardly rectifying channel subfamily J member 2 (KCNJ2) in OS is unclear. Methods The expression of KCNJ2 in OS tissues and cell lines was measured using bioinformatic analysis, immunohistochemistry, and western blotting. Wound-healing assays, Transwell assays, and lung metastasis models were used to analyze the effects of KCNJ2 on mobility of OS cells. The molecular mechanisms linking KCNJ2 and HIF1α in OS were explored by mass spectrometry analysis, immunoprecipitation, ubiquitination detection, and chromatin-immunoprecipitation quantitative real-time polymerase chain reaction. Results KCNJ2 was found to be overexpressed in advanced-stage OS tissues, as well as in cells with high metastatic potential. High expression of KCNJ2 was associated with a shorter survival rate of OS patients. KCNJ2-inhibition repressed the metastasis of OS cells, whereas KCNJ2-elevation induced the opposite effects. Mechanistically, KCNJ2 binds to HIF1α and inhibits its ubiquitination, thus increasing the expression of HIF1α. Interestingly, HIF1α binds directly to the KCNJ2 promoter and increases its transcription under hypoxic conditions. Conclusion Taken together, our results indicated that a KCNJ2/HIF1α positive feedback loop exists in OS tissues, which significantly promotes OS cell metastasis. This evidence may contribute to the diagnosis and treatment of OS. Video Abstract

Abstract This study addresses the meso-structure of recycled aggregate concrete with different admixture and c;uring condition. The RCA (Recycled concrete aggregate) with admixture of slag power and fly ash and curing condition of steam was casted. X-ray CT (Computed tomography) was used to obtain meso-structure of RCA, and the pore structure, aggregate, and interface traction zone were analyzed. The results show that steam curing not only increases the pore volume but also makes the pore morphology more complex, the fractal dimension increases, the proportion of spherical pores decreases, and the pores develop from spherical to flat and slender with the increase of steam curing temperature. The porosity of micron pores in recycled aggregate concrete is about 2.3%, in which the pores with aperture less than 300 μm accounts for more than 85%. The thickness of the interface area between recycled aggregate and new mortar is about 200 μm, and the crack width in recycled aggregate is about 300– 400 μm.

The ultra-fine dredged sand (DS) from the lower reaches of the Yangtze River is a large amount of solid waste with the potential to be recycled and applied as a replacement for fine aggregate. This article discussed the utilization of dredged sand by producing alkali activated materials (AAMs). The chemical and physical characteristics of the DS were analyzed. The effect of the DS on durability and mechanical characteristics of the alkali activated slag/fly materials were studied with different precursor systems. From the results, it was found that the addition of DS improved the 28 d strength and even 56 d strength. The 25% DS content increased the compressive strength of both slag rich and fly ash (FA) rich AAMs by about 5%, and the microstructure showed a denser matrix at this content. However, excessive DS can cause a decrease in flowability, early compressive strength and a decline in the compactness of the matrix. Adding an appropriate amount of DS can control the drying shrinkage. The 25% DS content has an inhibitory effect on the shrinkage development of slag rich mortar, while the similar effect on FA rich mortar appears at a content of over 50%. The adoption of DS addition to produce AAMs improves the ecological benefits of concrete engineering projects on the Yangtze River coast.

Foamed concrete, due to its lightweight and high-strength characteristics, offers significant advantages as a roadbed material. However, its mechanical properties are notably influenced by its density and microstructure. Comprehensive research addressing the correlation between the density, mechanical properties, and microstructure of roadbed foamed concrete, especially within real construction scenarios, remains limited. To address this research gap, we undertook compressive strength tests and a set of microstructural analyses on four sets foamed concrete samples of varying densities prepared on-site. The objective was to deeply understand the mechanical and microstructural characterization of roadbed foamed concrete at different densities and correlation Analysis. The findings indicate an exponential correlation between density and compressive strength, most prominently within the density range of 800–1000 kg/m3, accompanied by commendable thermal stability. X-ray Computed Tomography (X-CT) analyses further demonstrate that density increase is pivotal in enhancing the pore structure, thereby achieving lower porosity, fewer detrimental pores, more homogeneous pore distribution, and superior pore sphericity. Scanning Electron Microscopy (SEM) evaluations suggest that enhancing the density of the sample can mitigate the damage to individual pores, reduce internal cavities, and curb initial defects. Furthermore, the pore intersections exhibit a more intact and dense crystalline structure. Upon assessment, we discerned a significant correlation between porosity, compressive strength, and density. The Pearson correlation coefficient (r) between any two of these parameters is notably close to 1 (−1). These research results show that it is feasible to optimize the density of foam concrete to enhance its microstructure and thereby enhance its compressive performance. This provides strong data support for the wider application of foam concrete in roadbed engineering.

Introduction: As psychoneuroimmunology flourishes, there is compelling evidence that depression suppresses the anti-tumor immune response, promotes the progression of cancer, and inhibits the effectiveness of cancer immunotherapy. Recent studies have reported that antidepressants can not only alleviate the depressant condition of cancer patients, but also strengthen the anti-tumor immunity, thus suppressing tumors. Tumor necrosis factor receptor 2 (TNFR2) antagonistic antibodies (Anti-TNFR2) targeting tumor-infiltrating regulatory T cells (Tregs) has achieved great results in preclinical studies, and with a favorable toxicity profile than existing immunotherapies, and is expected to become a new generation of more effective treatment strategies. Understanding the effects of combination therapy with antidepressants and Anti-TNFR2 may help design new strategies for cancer immunotherapy.Methods: We treated CT26, HCT116, MCA38 and SW620 colon cancer cells with fluoxetine (0–50 µM), ansofaxine hydrochloride (0–50 µM) and amitifadine hydrochloride (0–150 µM) to examine their effects on cell proliferation and apoptosis. We explored the antitumor effects of ansofaxine hydrochloride in combination with or without Anti-TNFR in subcutaneously transplanted CT26 cells in tumor-bearing mouse model. Antitumor effects were evaluated by tumor volume. NK cell, M1 macrophage cell, CD4+ T cell, CD8+ T cell, exhausted CD8+ T and regulatory T cell (Tregs) subtypes were measured by flow cytometry. 5-hydroxytryptamine, dopamine and norepinephrine levels were measured by ELISA.Results: Oral antidepression, ansofaxine hydrochloride, enhanced peripheral dopamine levels, promoted CD8+T cell proliferation, promoted intratumoral infiltration of M1 and NK cells, decreased the proportion of tumor-infiltrating exhausted CD8+T cells, and strengthened anti-tumor immunity, thereby inhibiting colon cancer growth. In combination therapy, oral administration of ansofaxine hydrochloride enhanced the efficacy of Anti-TNFR2, and produced long-term tumor control in with syngeneic colorectal tumor-bearing mice, which was attributable to the reduction in tumor-infiltrating Treg quantity and the recovery of CD8+ T cells function.Discussion: In summary, our data reveal the role of ansofaxine hydrochloride in modulating the anti-tumor immunity. Our results support that exhausted CD8+T is an important potential mechanism by which ansofaxine hydrochloride activates anti-tumor immunity and enhances anti-tumor effects of anti-TNFR2.

Embryonic stem cells (ESCs) are remarkably undifferentiated cells that originate from the inner cell mass of the blastocyst. They possess the ability to self-renew and differentiate into multiple cell types, making them invaluable in diverse applications such as disease modeling and the creation of transgenic animals. In recent years, as agricultural practices have evolved from traditional to biological breeding, it has become clear that pluripotent stem cells (PSCs), either ESCs or induced pluripotent stem cells (iPSCs), are optimal for continually screening suitable cellular materials. However, the technologies for long-term in vitro culture or establishment of cell lines for PSCs in livestock are still immature, and research progress is uneven, which poses challenges for the application of PSCs in various fields. The establishment of a robust in vitro system for these cells is critically dependent on understanding their pluripotency maintenance mechanisms. It is believed that the combined effects of pluripotent transcription factors, pivotal signaling pathways, and epigenetic regulation contribute to maintaining their pluripotent state, forming a comprehensive regulatory network. This article will delve into the primary mechanisms underlying the maintenance of pluripotency in PSCs and elaborate on the applications of PSCs in the field of livestock.

The perception systems of autonomous vehicles face significant challenges under adverse conditions, with issues such as obscured objects and false detections due to environmental noise. Traditional approaches, which typically focus on noise removal, often fall short in such scenarios. Addressing the lack of diverse adverse weather data in existing automotive datasets, we propose a novel data augmentation method that integrates realistically simulated adverse weather effects into clear condition datasets. This method not only addresses the scarcity of data but also effectively bridges domain gaps between different driving environments. Our approach centers on a conditional generative model that uses segmentation maps as a guiding mechanism to ensure the authentic generation of adverse effects, which greatly enhances the robustness of perception and object detection systems in autonomous vehicles, operating under varied and challenging conditions. Besides the capability of accurately and naturally recreating over 90% of the adverse effects, we demonstrate that this model significantly improves the performance and accuracy of deep learning algorithms for autonomous driving, particularly in adverse weather scenarios. In the experiments employing our augmented approach, we achieved a 2.46% raise in the 3D average precision, a marked enhancement in detection accuracy and system reliability, substantiating the model’s efficacy with quantifiable improvements in 3D object detection compared to models without augmentation. This work not only serves as an enhancement of autonomous vehicle perception systems under adverse conditions but also marked an advancement in deep learning models in adverse condition research.

Transformer-based models have gained popularity in the field of natural language processing (NLP) and are extensively utilized in computer vision tasks and multi-modal models such as GPT4. This paper presents a novel method to enhance the explainability of transformer-based image classification models. Our method aims to improve trust in classification results and empower users to gain a deeper understanding of the model for downstream tasks by providing visualizations of class-specific maps. We introduce two modules: the “Relationship Weighted Out” and the “Cut” modules. The “Relationship Weighted Out” module focuses on extracting class-specific information from intermediate layers, enabling us to highlight relevant features. Additionally, the “Cut” module performs fine-grained feature decomposition, taking into account factors such as position, texture, and color. By integrating these modules, we generate dense class-specific visual explainability maps. We validate our method with extensive qualitative and quantitative experiments on the ImageNet dataset. Furthermore, we conduct a large number of experiments on the LRN dataset, which is specifically designed for automatic driving danger alerts, to evaluate the explainability of our method in scenarios with complex backgrounds. The results demonstrate a significant improvement over previous methods. Moreover, we conduct ablation experiments to validate the effectiveness of each module. Through these experiments, we are able to confirm the respective contributions of each module, thus solidifying the overall effectiveness of our proposed approach.

Abstract The dynamic response properties of concrete have been of interest during the use of buildings due to seismic, impact, and explosion events. The splitting Hopkinson lever is a classical device for testing the dynamic mechanical properties of materials. In this paper, dynamic splitting tests on concrete were conducted using it, and a time series predictive computational model for the incident, reflected and transmitted pulses of high-strength concrete specimens at high strain rates was developed, and the extension mechanism of splitting tensile cracks in high-strength concrete was detected and analyzed based on the DIC technique. The results show that: the peak strength of C60 specimens and C80 specimens increased by about 60% and 90%, respectively, from 0.05 MPa to 0.09 MPa in impact strength; the triangular damaged area at the end of the contact surface of the specimen and the rod subjected to high impact pressure increased significantly, the dynamic energy dissipation increased, and the damage degree of the specimens increased; under the action of high strain rate, the brittleness of the concrete specimens with higher strength increased, the damage rate The higher strength concrete specimens have increased brittleness, faster damage rate and higher crack extension under high strain rate. The results of the paper can provide important references for the design of buildings under impact loading.

In recent years, inducing pluripotent stem cells to differentiate into functional primordial germ cells (PGCs) in vitro has become an important method of obtaining a large number of PGCs. However, the instability and low induction efficiency of the in vitro PGC induction system restrict the application of PGCs in transgenic animal production, germplasm resource conservation and other fields. In this study, we successfully established a two-step induction model of chicken PGCs in vitro, which significantly improved the formation efficiency of PGC-like cells (PGCLCs). To further improve the PGC formation efficiency in vitro, 5025 differentially expressed genes (DEGs) were obtained between embryonic stem cells (ESCs) and PGCs through RNA-seq. GO and KEGG enrichment analysis revealed that signaling pathways such as BMP4, Wnt and Notch were significantly activated during PGC formation, similar to other species. In addition, we noted that cAMP was activated during PGC formation, while MAPK was suppressed. Based on the results of our analysis, we found that the PGC formation efficiency was significantly improved after activating Wnt and inhibiting MAPK, and was lower than after activating cAMP. To sum up, in this study, we successfully established a two-step induction model of chicken PGCs in vitro with high PGC formation efficiency, which lays a theoretical foundation for further demonstrating the regulatory mechanism of PGCs and realizing their specific applications.

Abstract There are different characteristics of BC in developing countries and developed countries. We intended to study the factors which influence the survival and prognosis of BC between southern China and the United States. (a) To study the two groups BC patients in southern China from 2001 to 2016 and SEER database from 1975 to 2016. (b) To register, collect and analyze the clinicopathological features and treatment information. Our study found that there are significant differences in tumor size, positive lymph node status and KI-67 between southern China and SEER cohort (P

ABSTRACT: Spermatogonia Stem Cells (SSCs) are the basis of spermatogenesis. In the poultry industry, asthenospermia and azoospermia in roosters seriously reduce economic benefits. In this study, we explored SSCs formation mechanisms in detail. TDRD1, which is a downstream target gene of TCF7L2 and is modified by histone methylation, was screened through multiomics analysis. Functionally, RT-qPCR, flow cytometry, immunohistochemistry, and indirect immunofluorescence results showed that H3K4me2 regulated TDRD1 to promote SSCs formation both in vivo and in vitro. Furthermore, ChIP-qPCR and dual luciferase assays showed that H3K4me2 was enriched in the −800 to 0 bp region of the TDRD1 promoter and positively regulated TDRD1 transcription to promote SSCs formation. Interestingly, in mechanistic terms, dual luciferase assays showed that TDRD1 transcription levels were significantly decreased after co-transfection with dCas9-LSD1-P1/P2/P3 and OETCF7L2, while TDRD1 transcript levels were not significantly altered after transfecting dCas9-LSD1-P4 and OETCF7L2. These results suggested that H3K4me2 enrichment in P1, P2, and P3 of the TDRD1 promoter promotes TDRD1 transcription by reducing enrichment of TCF7L2. This study explored the specific regulatory mechanisms involving the Wnt signaling pathway, H3K4me2, and TDRD1, enriched the regulatory network regulating the formation of SSCs, and laid a theoretical foundation for the specific application of SSCs.

LiDAR point clouds are significantly impacted by snow in driving scenarios, introducing scattered noise points and phantom objects, thereby compromising the perception capabilities of autonomous driving systems. Current effective methods for removing snow from point clouds largely rely on outlier filters, which mechanically eliminate isolated points. This research proposes a novel translation model for LiDAR point clouds, the ‘L-DIG’ (LiDAR depth images GAN), built upon refined generative adversarial networks (GANs). This model not only has the capacity to reduce snow noise from point clouds, but it also can artificially synthesize snow points onto clear data. The model is trained using depth image representations of point clouds derived from unpaired datasets, complemented by customized loss functions for depth images to ensure scale and structure consistencies. To amplify the efficacy of snow capture, particularly in the region surrounding the ego vehicle, we have developed a pixel-attention discriminator that operates without downsampling convolutional layers. Concurrently, the other discriminator equipped with two-step downsampling convolutional layers has been engineered to effectively handle snow clusters. This dual-discriminator approach ensures robust and comprehensive performance in tackling diverse snow conditions. The proposed model displays a superior ability to capture snow and object features within LiDAR point clouds. A 3D clustering algorithm is employed to adaptively evaluate different levels of snow conditions, including scattered snowfall and snow swirls. Experimental findings demonstrate an evident de-snowing effect, and the ability to synthesize snow effects.

ATM serine/threonine kinase (ATM; previously known as ataxia‐telangiectasia mutated) plays a critical role in maintaining genomic stability and regulates multiple downstream pathways, such as DNA repair, cell cycle arrest, and apoptosis. As a serine/threonine kinase, ATM has an array of downstream phosphorylation substrates, including checkpoint effector checkpoint kinase 2 (CHK2). ATM inhibits cell cycle progression by phosphorylating and activating CHK2, which plays an important role in the formation and development of tumors and participates in DNA repair responses after double‐stranded DNA breaks. In this study, we used a recently developed mammalian functional genetic screening system to explore a series of ATM substrates and their role in DNA damage to enhance our understanding of the DNA damage response. Ubiquilin 4 (UBQLN4), which belongs to the ubiquilin family characterized by its ubiquitin‐like (UBL) and ubiquitin‐associated (UBA) domains, was identified as a new substrate for ATM. UBQLN4 is involved in various intracellular processes, such as autophagosome maturation, p21 regulation, and motor axon morphogenesis. However, the biological function of UBQLN4 remains to be elucidated. In this study, we not only identified UBQLN4 as a substrate for ATM, but also found that UBQLN4 interacts with and stabilizes the anti‐apoptotic proteins Bcl‐2‐related protein A1 (BCL2A1) and Bcl‐2‐like protein 10 (BCL2L10) and prevents mesothelioma cell apoptosis in response to DNA damage. These findings expand our understanding of the role of UBQLN4 in mesothelioma and provide new insights into potential mesothelioma treatments targeting substrates for ATM.

In order to study the failure characteristics of old age concrete, five different loading rates (0.02 mm/min ~ 1.5 mm/min) were used to carry out uniaxial compression tests on 60-year-old bridge concrete cores. The Digital Image Correlation (DIC) method was used for non-contact full field deformation observation of crack evolution. At the same time, the cumulative counts, event number and amplitude were used as the characterization parameters of Acoustic Emission (AE) technology to monitor the concrete damage process. The results show that the ultimate strength, the number of cracks, and the severity of failure of aged concrete increased with the increase of loading rate, while the number of AE events decreased with the increasing loading rate. And the compressive strength of the old bridge concrete is 26.3 MPa, which is 24.5% lower than the design strength of 35 MPa.There is an obvious compaction stage of aged concrete under different loading rates compared with early age concrete, and the slope of the stress-strain curve in this stage increased continuously. When the specimen was damaged, the initial cracks developed vertically and then obliquely, the overall failure of the specimen is caused by tensile cracks.

BackgroundsProstate cancer (PCa) is the second most common male cancer in the world and based on its high prevalence and overwhelming effect on patients, more precise diagnostic and therapeutic methods are essential research topics. As such, this study aims to evaluate the value of three-dimensional transrectal ultrasound (3D-TRUS) in the detection, diagnosis and biopsy of PCa, and to provide a basis for clinical practice of PCa.MethodsRetrospective analysis and comparison of a total of 401 male patients who underwent prostate TRUS in our hospital from 2019 to 2020 were conducted, with all patients having prostate biopsy. Nomogram was used to estimate the probability of different ultrasound signs in diagnosing prostate cancer. The ROC curve was used to estimate the screening and diagnosis rates of 3D-TRUS, MRI and TRUS for prostate cancer.ResultsA total of 401 patients were randomly divided into two groups according to different methods of prostate ultrasonography, namely the TRUS group (251 patients) and the 3D-TRUS group (150 patients). Of these cases, 111 patients in 3D-TRUS group underwent MRI scan. The nomogram further determined the value of 3D-TRUS for prostate cancer. The ROC AUC of prostate cancer detected by TRUS, MRI and 3D-TRUS was 0.5580, 0.6216 and 0.6267 respectively. Biopsy complications were lower in 3D-TRUS group than TRUS group, which was statistically significant (P

Objective: FGFR is considered an important driver gene of lung squamous cell carcinoma (LSCC). Thus, identification of the biological events downstream of FGFR is important for the treatment of this malignancy. Our previous study has shown that the FGFR/RACK1 complex interacts with PKM2 and consequently promotes glycolysis in LSCC cells. However, the biological functions of the FGFR/RACK1 complex remain poorly understood. Methods: Anchorage-independent assays and in vivo tumorigenesis assays were performed to evaluate cancer cell malignancy. Distant seeding assays were performed to evaluate cancer cell metastasis. β-gal staining was used to examine cell senescence, and immunoprecipitation assays were performed to examine the interactions among FGFR, RACK1, and MDM2. Results: FGFR/RACK1 was found to regulate the senescence of LSCC cells. Treatment with PD166866, an inhibitor of FGFR, or knockdown of RACK1 induced senescence in LSCC cells (P < 0.01). A molecular mechanistic study showed that FGFR/RACK1/MDM2 form a complex that promotes the degradation of p53 and thus inhibits cell senescence. PD166866 and RG7112, an MDM2/p53 inhibitor, cooperatively inhibited the colony formation and distal seeding of LSCC cells (P < 0.01), and upregulated the expression of p53 and p21. Conclusions: Together, our findings revealed the regulatory roles and mechanisms of FGFR/RACK1 in cell senescence. This understanding should be important in the treatment of LSCC.

Abstract Bispecific antibodies (bsAb) that target two independent epitopes or antigens have been extensively explored in translational and clinical studies since they were first developed in the 1960s. Many bsAbs are being tested in clinical trials for treating a variety of diseases, mostly cancer. Here, we provide an overview of various types of bsAbs in clinical studies and discuss their targets, safety profiles, and efficacy. We also highlight the current challenges, potential solutions, and future directions of bsAb development for cancer treatment.

Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder with the underlying etiology yet incompletely understood and no cure treatment. Patients of fragile X syndrome (FXS) also manifest symptoms, e.g. deficits in social behaviors, that are core traits with ASD. Several studies demonstrated that a mutual defect in retinoic acid (RA) signaling was observed in FXS and ASD. However, it is still unknown whether RA replenishment could pose a positive effect on autistic-like behaviors in FXS. Herein, we found that RA signaling was indeed down-regulated when the expression of FMR1 was impaired in SH-SY5Y cells. Furthermore, RA supplementation rescued the atypical social novelty behavior, but failed to alleviate the defects in sociability behavior or hyperactivity, in Fmr1 knock-out (KO) mouse model. The repetitive behavior and motor coordination appeared to be normal. The RNA sequencing results of the prefrontal cortex in Fmr1 KO mice indicated that deregulated expression of Foxp2, Tnfsf10, Lepr and other neuronal genes was restored to normal after RA treatment. Gene ontology terms of metabolic processes, extracellular matrix organization and behavioral pathways were enriched. Our findings provided a potential therapeutic intervention for social novelty defects in FXS.

Ultra-fine sands are dredged periodically in order to maintain the normal activities of the Yangtze River Channel. Finding a new solution for managing these ultra-fine dredged sand becomes a challenge for channel managers. In this study, ultra-fine dredged sand and manufactured sand were used as the concrete fine aggregates. The concrete mix ratio was obtained based on the minimum paste theory by setting different target strengths, Average Paste Thickness (APT) between aggregates and dredged sand contents. The feasibility of applying the minimum paste theory in the design of ultra-fine dredged sand concrete mix ratio was verified by compressive strength tests. The influences of APT and dredged sand content on the mechanical properties and workability of concrete were analyzed. The results showed that with the increase of the APT, the compressive strength initially was increased and then decreased and the workability was improved. The workability of the concrete was improved with more content of ultra-fine dredged sand through the analysis of the microstructure of the fine aggregates. The concrete with a mass ratio 25% ultra-fine dredged sand had a lower harmful porosity which was verified by mercury intrusion porosimetry (MIP) and SEM, and has a compressive strength value of 43.8 MPa at 28 days which was 11.4% and 10.61% higher than that of the control group with the content ratio of 0% and 50%, respectively. The test results proved that the use of the minimum paste theory in the design of the ultra-fine dredged sand concrete mix ratio is expected to obtain concrete with fewer paste content and proper working performance.

In order to study the fracture behavior of hydraulic concrete, wedge splitting tests are performed on notched cubic concrete specimens with different crack-depth ratios (0.3, 0.4, and 0.5). Meanwhile, acoustic emission and the digital image correlation method were used to monitor the crack propagation. Test results show that the initiation toughness of the hydraulic concrete specimen is independent of the crack-depth ratio. As the crack-depth ratio increases, the fracture toughness, the fracture energy, and the critical crack length decrease. The AE cumulative counts and hits can reflect not only the four-stages fracture process of hydraulic concrete but also the boundary effect of hydraulic concrete. The acoustic emission b value can reflect the two stages of postpeak damage of the hydraulic concrete. The length of fictitious crack, the propagation velocity of macrocrack and effective crack length decrease with the increase of the initial notch depth ratio. The effective crack length increases with the increase in the maximum aggregate size, and the growth time increases with the maximum aggregate size and an effective height of the specimen.

The use of recycled aggregates to produce precast concrete products is conductive to the green development of construction industrialization. This paper aimed to study the effects of curing regimes and confining pressures on the triaxial compression behavior of recycled aggregate concrete (RAC). Triaxial compression tests were carried out on RAC under different curing regimes (standard curing, 60 °C—12 h and 80 °C—9 h), and the designed confining pressures were 0 MPa, 2.5 MPa, 5 MPa, and 10 MPa. The results show that the increase of confining pressure limits the expansion of cracks, causing the failure mode to change from vertical splitting to oblique shearing, and the triaxial compressive strength is doubled at most. Compared with standard curing, steam curing significantly weakened the triaxial compressive strength of RAC, which was related to the reduction of RAC cohesion, and the cohesion of RAC steam cured at 80 °C was reduced by 30%. The triaxial compression failure of RAC closely follows the Mohr–Coulomb criterion. Based on the discrete element method and test results, an RAC triaxial compression numerical model considering the shape of the actual coarse aggregate was established, and the propagation of cracks was discussed at the mesoscopic level.

Cell adhesion plays an important role in the differentiation of the morphogenesis and the trophectoderm epithelium of the blastocyst. In the porcine embryo, CDH1 mediated adhesion initiates at compaction before blastocyst formation, regulated post-translationally via protein kinase C and other signaling molecules. Here we focus on muscle RAS oncogene homolog (M-RAS), which is the closest relative to the RAS related proteins and shares most regulatory and effector interactions. To characterize the effects of M-RAS on embryo compaction, we used gain- and loss-offunction strategies in porcine embryos, in which M-RAS gene structure and protein sequence are conserved. We showed that knockdown of M-RAS in zygotes reduced embryo development abilities and CDH1 expression. Moreover, the phosphorylation of ERK was also decreased in M-RAS KD embryos. Overexpression of M-RAS allows M-RAS KD embryos to rescue the embryo compaction and blastocyst formation. Collectively, these results highlight novel conserved and multiple effects of M-RAS during porcine embryo development.

To investigate the genetic variation and molecular epidemiology characteristics of Human Respiratory Syncytial Virus (HRSV) in Guizhou Province, nasopharyngeal aspirates were collected from patients with acute respiratory infection (ARI) in Guizhou Provincial People's Hospital, from December 2017 to March 2018, and inoculated to Hep-2 cells to isolate HRSV. Cells that showed cytopathic effect (CPE) were then confirmed by indirect immunofluorescence assay and reverse transcription. The sequence of the PCR products was determined for HRSV isolates, and the genetic variation was analyzed. Out of 196 nasopharyngeal aspirate samples, HRSV were isolated in 39. The second hypervariable region at the 3′ terminal of glycoprotein gene (HVR2) sequence analysis showed that subgroup A was dominant. Seventy-nine percent of the isolates belonged to subgroup A, ON1 genotype, and 21 % belonged to subgroup B, BA9 genotype, which indicates that the dominant HRSV circulating in Guizhou Province was subgroup A, genotype ON1, co-circulating with a less prevalent subgroup B, genotype BA9. Keywords: Human respiratory syncytial virus, Virus isolation, RT-PCR, HVR2, Phylogenetic analysis, Molecular epidemiology

BackgroundHypoxia is associated with the development of pancreatic cancer (PC). However, genes associated with hypoxia response and their regulatory mechanism in PC cells were unclear. The current study aims to investigate the role of the hypoxia associated gene fucosyltransferase 11 (FUT11) in the progression of PC.MethodsIn the preliminary study, bioinformatics analysis predicted FUT11 as a key hypoxia associated gene in PC. The expression of FUT11 in PC was evaluated using quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry. The effects of FUT11 on PC cells proliferation and migration under normoxia and hypoxia were evaluated using Cell Counting Kit 8, 5-ethynyl-2’-deoxyuridine (EDU) assay, colony formation assay and transwell assay. The effects of FUT11 in vivo was examined in mouse tumor models of liver metastasis and subcutaneous xenograft. Furthermore, Western blot, luciferase assay and immunoprecipitation were performed to explore the regulatory relationship among FUT11, hypoxia-inducible factor 1α (HIF1α) and pyruvate dehydrogenase kinase 1 (PDK1) in PC.ResultsFUT11 was markedly increased of PC cells with hypoxia, upregulated in the PC clinical tissues, and predicted a poor outcome of PC patients. Inhibition of FUT11 reduced PC cell growth and migratory ability of PC cells under normoxia and hypoxia conditions in vitro, and growth and tumor cell metastasis in vivo. FUT11 bound to PDK1 and regulated the expression PDK1 under normoxia and hypoxia. FUT11 interacted with PDK1 and decreased the ubiquitination of PDK1, lead to the activation of AKT/mTOR signaling pathway. FUT11 knockdown significantly increased the degradation of PDK1 under hypoxia, while treatment with MG132 can relieve the degradation of PDK1 induced by FUT11 knockdown. Overexpression of PDK1 in PC cells under hypoxia conditions reversed the suppressive impacts of FUT11 knockdown on PC cell growth and migration. In addition, HIF1α bound to the promoter of FUT11 and increased its expression, as well as co-expressed with FUT11 in PC tissues. Furthermore, overexpression of FUT11 partially rescued the suppressive effects of HIF1α knockdown on PC cell growth and migration in hypoxia condition.ConclusionOur data implicate that hypoxia-induced FUT11 contributes to proliferation and metastasis of PC by maintaining the stability of PDK1, thus mediating activation of AKT/mTOR signaling pathway, and suggest that FUT11 could be a novel and effective target for the treatment of pancreatic cancer.

Candida parapsilosis is a major fungal pathogen that leads to sepsis. New and more effective antifungal agents are required due to the emergence of resistant fungal strains. MAF-1A is a cationic antifungal peptide isolated from Musca domestica that is effective against a variety of Candida species. However, the mechanism(s) of its antifungal activity remains undefined. Here, we used RNA-seq to identify differentially expressed genes (DEGs) in Candida parapsilosis following MAF-1A exposure. The early (6 h) response included 1,122 upregulated and 1,065 downregulated genes. Late (18 h) responses were associated with the increased expression of 101 genes and the decreased expression of 151 genes. Upon MAF-1A treatment for 18 h, 42 genes were upregulated and 25 genes were downregulated. KEGG enrichment showed that the DEGs in response to MAF-1A were mainly involved in amino acid synthesis and metabolism, oxidative phosphorylation, sterol synthesis, and apoptosis. These results indicate that MAF-1A exerts antifungal activity through interference with Candida parapsilosis cell membrane integrity and organelle function. This provides new insight into the interaction between Candida parapsilosis and this antimicrobial peptide and serves as a reference for future Candida parapsilosis therapies.

Abstract Background Rift Valley Fever (RVF) is a mosquito-borne viral zoonosis. To detect RVF virus (RVFV) infection, indirect immunoglobulin G (IgG) and immunoglobulin M (IgM) enzyme linked immunosorbent assays (ELISAs) which utilize recombinant RVFV nucleocapsid (RVFV-N) protein as assay antigen, have reportedly been used, however, there is still a need to develop more sensitive and specific methods of detection. Methods RVFV-N protein was expressed in Escherichia coli (E. coli) and purified by histidine-tag based affinity chromatography. This recombinant RVFV-N (rRVFV-N) protein was then used as antigen to develop an IgG sandwich ELISA and IgM capture ELISAs for human sera. Ninety six serum samples collected from healthy volunteers during the RVF surveillance programme in Kenya in 2013, and 93 serum samples collected from RVF-suspected patients during the 2006–2007 RVF outbreak in Kenya were used respectively, to evaluate the newly established rRVFV-N protein-based IgG sandwich ELISA and IgM capture ELISA systems in comparison with the inactivated virus-based ELISA systems. Results rRVFV-N protein-based-IgG sandwich ELISA and IgM capture ELISA for human sera were established. Both the new ELISA systems were in 100% concordance with the inactivated virus-based ELISA systems, with a sensitivity and specificity of 100%. Conclusions Recombinant RVFV-N is a safe and affordable antigen for RVF diagnosis. Our rRVFV-N-based ELISA systems are safe and reliable tools for diagnosis of RVFV infection in humans and especially useful in large-scale epidemiological investigation and for application in developing countries.

Summary: The nucleosome, the fundamental structural unit of chromatin, is a critical regulator of gene expression. The mechanisms governing changes to nucleosome occupancy and positioning during somatic cell reprogramming remain poorly understood. We established a method for generating genome-wide nucleosome maps of porcine embryonic fibroblasts (PEF), reconstructed 1-cell embryos generated by somatic cell nuclear transfer (SCNT), and fertilized zygotes (FZ) using MNase sequencing with only 1,000 cells. We found that donor PEF chromatin, especially X chromosome, became more open after transfer into porcine oocytes and nucleosome occupancy decreased in promoters but increased in the genic regions. Nucleosome arrangements around transcriptional start sites of genes with different expression levels in somatic cells tended to become transcriptionally silent in SCNT; however, some pluripotency genes adopted transcriptionally active nucleosome arrangements. FZ and SCNT had similar characteristics, unlike PEF. This study reveals the dynamics and importance of nucleosome positioning and chromatin organization early after reprogramming. : Liu, Miao, and colleagues explore the chromosome dynamics during reprogramming of porcine fibroblasts after SCNT. By applying MNase-seq with low cell input, which is particularly important for scarce biological samples, they reveal a dynamic reorganization of nucleosomes during reprogramming. Keywords: nucleosome organization, PEF, SCNT, handmade cloning, FZ, reprogramming, gene expression

Resistance to radiotherapy is frequently observed in the clinic and leads to poor prognosis of non-small cell lung cancer (NSCLC). How to overcome resistance to radiotherapy is a challenge in the treatment of NSCLC. In this study, PPDPF was found to be upregulated in NSCLC tissues and cell lines, and its expression negatively correlated with the overall survival of patients with NSCLC. PPDPF promoted the growth, colony formation and invasion of lung cancer cells. Moreover, knockout of PPDPF inhibited tumorigenesis in the KL (Kras G12D ; LKB1 f/f ) mouse model of lung cancer. Additionally, overexpression of PPDPF led to radioresistance in lung cancer cells, and knockdown of PPDPF sensitized lung cancer cells to radiotherapy. Mechanistically, PPDPF interacted with BABAM2 (an antiapoptotic protein) and blocked its ubiquitination by MDM2, thus stabilizing BABAM2 and promoting the radioresistance of lung cancer cells. Our present study suggested PPDPF as a therapeutic target in NSCLC., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Aberrant activation of Hedgehog-Gli1 signaling and accumulation of Gli1 in hepatocellular carcinoma (HCC) are frequently observed. However, the mechanisms leading to the overactivation of this signaling pathway are not fully understood. In this study, we show that the short isoform of PHD finger protein 19 (PHF19) interacts with β-TrCP, the E3 ligase of Gli1, and that knocking down PHF19 promotes the ubiquitination of Gli1. In a biological function study, PHF19 was found to promote the growth of HCC cells both in liquid culture and in soft agar. Moreover, knocking out PHF19 in a HCC mouse model (Myc F/F ) using the hydrodynamic method inhibited tumorigenesis and improved survival. Taken together, these results demonstrate that PHF19 promotes the growth of HCC cells by activating the Hedgehog signaling pathway., (Copyright © 2021. Published by Elsevier Inc.)