Search

Abstract Purpose This study aims to summarize the latest and best evidence on central venous access device-related thrombosis (CRT) in hospitalized children, which provides theoretical support for standardizing the preventive care practice of CRT in hospitalized children. Methods Relevant guidelines, systematic reviews and expert consensuses were reviewed through ten guideline websites, six professional association websites and seven databases. The literature evaluation was conducted, and the best evidence from qualified studies was extracted and summarized. Furthermore, the best evidence was summarized through expert consultation and localized for the preventive care practice of CRT in hospitalized children in China. Results A total of 14 topics and 68 best evidence were collected, including personnel qualification and quality management, pediatric patient selection, risk assessment, central venous access device (CVAD) selection and use, tip position, catheter maintenance, basic prevention, drug prevention, imaging examination, health education, nursing records, follow-up, CVAD removal and others. Conclusion In this study, the best evidence based on evidence-based nursing was summarized, and expert consultation was adopted to localize the best evidence collected. It is of great significance to standardize the clinical practice of pediatric nurses and ensure the effectiveness of CRT preventive care for hospitalized children, thus guaranteeing the safety of hospitalized children with CVAD catheterization.

The kidney-brain axis is a bidirectional communication network connecting the kidneys and the brain, potentially affected by inflammation, uremic toxin, vascular injury, neuronal degeneration, and so on, leading to a range of diseases. Numerous studies emphasize the disruptions of the kidney-brain axis may contribute to the high morbidity of neurological disorders, such as cognitive impairment (CI) in the natural course of chronic kidney disease (CKD). Although the pathophysiology of the kidney-brain axis has not been fully elucidated, epidemiological data indicate that patients at all stages of CKD have a higher risk of developing CI compared with the general population. In contrast to other reviews, we mentioned some commonly used medicines in CKD that may play a pivotal role in the pathogenesis of CI. Revealing the pathophysiology interactions between kidney damage and brain function can reduce the potential risk of future CI. This review will deeply explore the characteristics, indicators, and potential pathophysiological mechanisms of CKD-related CI. It will provide a theoretical basis for identifying CI that progresses during CKD and ultimately prevents and treats CKD-related CI.

The global spread of viral respiratory infections continues to pose a substantial threat to human health, exacerbating the societal burden. Timely and precise detection of viruses is pivotal in mitigating pandemic transmission. Currently, the prevalent diagnostic techniques for viruses include real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and colloidal gold assays. However, intricate workflows and protracted processing times of RT-qPCR and ELISA preclude real-time diagnostics, despite their high accuracy. Colloidal gold assays offer rapid turnaround. However, their accuracy and sensitivity are limited, particularly in the context of emerging variants like SARS-CoV-2, which renders them suboptimal test tools. Mounting evidence suggests that surface-enhanced Raman spectroscopy (SERS), with its streamlined operation, rapid analysis, high specificity and sensitivity, holds significant potential as a superior alternative test tool. This review consolidates various SERS-based approaches for detecting respiratory infection virus (RIV) and delineates their characteristics. The unique strengths of SERS technology, including its exceptional sensitivity, robust specificity, and expedited turnaround times, earmark it as particularly well-suited for large-scale instant screening of viral infections within populations.

ABSTRACT: Four experiments were performed to investigate the role of the mitogen-activated protein kinase (MAPK) signaling pathway in intestinal absorption of phosphorus (P) and calcium (Ca) in broiler chickens. Experiment 1 assessed how dietary levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) influence the gene expression of intestinal P and Ca transporters in broilers. Experiment 2 evaluated the effects of 1,25(OH)2D3 administered via intraperitoneal injection on the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) signaling pathways. Experiments 3 and 4 investigated the effect of ERK and p38MAPK inhibitors on the expression of intestinal P and Ca transporters. The findings demonstrated that broilers (1–21 days old) fed a 1,25(OH)2D3-deficient diet (0.625 µg/kg) exhibited reduced body weight, tibia P and Ca levels, and mRNA levels of P transporters (NaPi-IIb, PiT-1, and PiT-2), Ca transporters (NCX1, PMCA1b, and CaBP-D28k), vitamin D receptors (VDR), ERK, and p38MAPK in the duodenum (Experiment 1) (P < 0.05). By comparison, the growth, bone quality, and mRNA levels of genes (except for duodenal NaPi-IIb) in broilers were similar to those in broilers fed the control diet when dietary 1,25(OH)2D3 was adequate (5 µg/kg) (Experiment 1) (P > 0.05). After intraperitoneal injection of 1,25(OH)2D3, the mRNA level of jejunal NaPi-IIb and the protein level of p-p38MAPK/t-p38MAPK in broilers (9–14 days old) decreased (P < 0.05), whereas the mRNA level of CaBP-D28k and the protein level of p-ERK/t-ERK increased (Experiment 2) (P < 0.05). The mRNA and protein expression of jejunal NaPi-IIb and the protein expression of CaBP-D28k in broilers (9–17 days old) treated with the ERK inhibitor PD98059 were greater than those in the control group (Experiment 3) (P < 0.05). Similarly, compared with control broilers, broilers (9–17 days old) treated with the p38MAPK inhibitor SB203580 showed elevated mRNA expression of jejunal NaPi-IIb and CaBP-D28k (Experiment 4) (P < 0.05). These results suggest that adequate supplementation with 1,25(OH)2D3 (5 µg/kg) can restore broiler growth and bone quality by upregulating the transcription of genes involved in intestinal P and Ca absorption. Additionally, the ERK and p38MAPK signaling pathways are implicated in the modulatory effect of 1,25(OH)2D3 on the absorption of P and Ca in broilers.

Abstract In order to address the challenges of identifying, detecting, and tracking moving objects in video surveillance, this paper emphasizes image-based dynamic entity detection. It delves into the complexities of numerous moving objects, dense targets, and intricate backgrounds. Leveraging the You Only Look Once (YOLOv3) algorithm framework, this paper proposes improvements in image segmentation and data filtering to address these challenges. These enhancements form a novel multi-object detection algorithm based on an improved YOLOv3 framework, specifically designed for video applications. Experimental validation demonstrates the feasibility of this algorithm, with success rates exceeding 60% for videos such as “jogging”, “subway”, “video 1”, and “video 2”. Notably, the detection success rates for “jogging” and “video 1” consistently surpass 80%, indicating outstanding detection performance. Although the accuracy slightly decreases for “Bolt” and “Walking2”, success rates still hover around 70%. Comparative analysis with other algorithms reveals that this method’s tracking accuracy surpasses that of particle filters, Discriminative Scale Space Tracker (DSST), and Scale Adaptive Multiple Features (SAMF) algorithms, with an accuracy of 0.822. This indicates superior overall performance in target tracking. Therefore, the improved YOLOv3-based multi-object detection and tracking algorithm demonstrates robust filtering and detection capabilities in noise-resistant experiments, making it highly suitable for various detection tasks in practical applications. It can address inherent limitations such as missed detections, false positives, and imprecise localization. These improvements significantly enhance the efficiency and accuracy of target detection, providing valuable insights for researchers in the field of object detection, tracking, and recognition in video surveillance.

2-Heptanol is an important secondary alcohol, applied in food, pharmaceutical and plastic industries. However, current industrial synthetic methods require energy intensive hydrogenation of 2-heptanone using homogeneous noble catalysts in alkaline medium. In this work, we presented a systematic study on enhanced transfer hydrogenation of 2-heptanone to 2-heptanol using non-noble Co/ZnO catalysts without alkaline promoters. The strong synergism of Co and ZnO contributes to formation of amorphous metallic Co species and electronically reconfigured CoO species, leading to a 20-fold activity enhancement at 180 °C and a TOF of 89.4 h−1 over Co0.09/ZnO-500 catalysts. Structure-dependency studies further revealed that, the lattice strain between Co and ZnO induced the generation of multi-phased Co/CoO/Co:ZnO interfaces, facilitating tandem H2 generation, spillover and activation of C=O bond (of 2-heptanone molecule), respectively. The insights of molecular catalysis on interface of amorphous Co/ZnO for enhanced C=O bond activation, provide fundamental understanding for transfer hydrogenation of various other ketones into valuable alcohols.

This case report describes a 16-year-old patient with refractory Hodgkin’s lymphoma who developed bilateral anterior and intermediate uveitis as an adverse reaction to Brentuximab vedotin (BV). This is a rare case of an ocular adverse reaction potentially related to BV, with symptoms like blurred vision, decreased visual acuity, photophobia, and redness. Potential mechanisms include BV targeting CD30+ T cells in the uveal tissue or an immune response triggered by the microtubule-disrupting agent MMAE within BV. This highlights the need for vigilant monitoring of ocular adverse events in BV-treated patients and further research into their mechanisms and management.

Dehydrogenation is considered as one of the most important industrial applications for renewable energy. Cubic ceria-based catalysts are known to display promising dehydrogenation performances in this area. Large particle size (>20 nm) and less surface defects, however, hinder further application of ceria materials. Herein, an alternative strategy involving lactic acid (LA) assisted hydrothermal method was developed to synthesize active, selective and durable cubic ceria of

Acquired pure red cell aplasia (aPRCA) is a rare hematological disorder characterized by normochromic, normocytic anemia, reticulocytopenia, and the absence of erythroblasts. The pathogenesis of aPRCA has remained elusive. This review delves into the intricate web of immune mechanisms underlying the development of this enigmatic condition. By exploring immune responses, cytotoxic effects, and antibody-mediated processes, we dissect the immune-driven assault on erythroid progenitors. The classification of aPRCA, including its primary and secondary forms, is elucidated, with a particular emphasis on etiological factors such as viruses, drugs, thymoma, and large granular lymphocytic leukemia. Furthermore, we discuss the implications of cytogenetic changes in erythroid progenitors and immune cells in the pathophysiology of aPRCA. This comprehensive overview aims to shed light on the complex interplay between immune dysregulation and erythroid failure in aPRCA, offering insights that will be crucial for better understanding and treating this disease.

Abstract Background Uric acid/high-density lipoprotein cholesterol ratio (UHR) is a novel index of inflammation and metabolism that has been investigated in various diseases. However, association between UHR and hypertension among reproductive-aged women is unclear. Methods In this cross-sectional study, we investigated the association between serum UHR and hypertension among 5485 women aged 20–44 years based on the National Health and Nutrition Examination Survey (NHANES) database using various methods, including univariate and multivariate logistic regression analysis, stratified analysis, and spline regression. P 1, P

Objective Our objective was to investigate the concentration of plasma thrombopoietin (TPO) in patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS), as well as its relationship with patients' responses to recombined human TPO (rhTPO) therapy.

Being the phylum with the second largest biodiversity, mollusks are widely distributed in marine, freshwater, and land, conquered almost all habitats on the earth. Throughout geological time, several molluscan lineages independently colonized freshwater and land, evolving independently in new habitats. Resolving the timing of their colonization for novel environments is the basis of understanding the complex evolution of Mollusca. Herein, we obtained an elaborate single–copy orthologs set including 107 genes with a total length of 3,447,675 amino acid sites across 134 mollusks to reconstruct the phylogeny of Mollusca. The phylogenetic analysis recovered the “Aculifera+ Conchifera” topology with well–supported. By the divergence times estimation with fossil calibration, we revealed Cambrian rapid diversification of all molluscan classes. What’s more, our results provided the times of three major independent colonization of novel environments and consistent with previous studies. The freshwater mussels (Bivalvia: Unionida) colonized freshwater about 233 Mya, ancient origin and late diversification make this order to become the main represent of the freshwater bivalves. The orders Stylommatophora and Basommatophora (Gastropoda: Pulmonata) respectively colonized land and freshwater about 201 Mya, the Triassic–Jurassic mass extinction may have provided the opportunities for their colonization. Ampullariidae (Gastropoda) colonized freshwater about 156 Mya, their lungs may have contributed to the adaption of tropical freshwater environment and make them survive. Our results probably offer the most comprehensive time–scale of molluscan evolution, could provide some insights into the habitat transition and evolution of Mollusca.

Three-dimensional skeleton-based action recognition (3D SAR) has gained important attention within the computer vision community, owing to the inherent advantages offered by skeleton data. As a result, a plethora of impressive works, including those based on conventional handcrafted features and learned feature extraction methods, have been conducted over the years. However, prior surveys on action recognition have primarily focused on video or red-green-blue (RGB) data-dominated approaches, with limited coverage of reviews related to skeleton data. Furthermore, despite the extensive application of deep learning methods in this field, there has been a notable absence of research that provides an introductory or comprehensive review from the perspective of deep learning architectures. To address these limitations, this survey first underscores the importance of action recognition and emphasizes the significance of 3-dimensional (3D) skeleton data as a valuable modality. Subsequently, we provide a comprehensive introduction to mainstream action recognition techniques based on 4 fundamental deep architectures, i.e., recurrent neural networks, convolutional neural networks, graph convolutional network, and Transformers. All methods with the corresponding architectures are then presented in a data-driven manner with detailed discussion. Finally, we offer insights into the current largest 3D skeleton dataset, NTU-RGB+D, and its new edition, NTU-RGB+D 120, along with an overview of several top-performing algorithms on these datasets. To the best of our knowledge, this research represents the first comprehensive discussion of deep learning-based action recognition using 3D skeleton data.

Extensive research has explored human motion generation, but the generated sequences are influenced by different motion styles. For instance, the act of walking with joy and sorrow evokes distinct effects on a character’s motion. Due to the difficulties in motion capture with styles, the available data for style research are also limited. To address the problems, we propose ASMNet, an action and style-conditioned motion generative network. This network ensures that the generated human motion sequences not only comply with the provided action label but also exhibit distinctive stylistic features. To extract motion features from human motion sequences, we design a spatial temporal extractor. Moreover, we use the adaptive instance normalization layer to inject style into the target motion. Our results are comparable to state-of-the-art approaches and display a substantial advantage in both quantitative and qualitative evaluations. The code is available at https://github.com/ZongYingLi/ASMNet.git.

ABSTRACT Streptococcus pneumoniae is a notorious human opportunistic pathogen which undergoes a spontaneous and reversible phenotypic change in response to the host environment. We demonstrated that the regulatory gene hsdSA of DNA methylation in the type I restriction modification system altered colony transparency and substantially contributed to S. pneumoniae virulence. Most importantly, hsdSA regulated the production of extracellular vesicles (EVs) which package cytosolic, surface, and secreted proteins, including pneumolysin (PLY). Interestingly, we confirmed that EV-associated PLY utilized internalization into macrophages to prolong the survival of intracellular bacteria as a major immune evasion strategy; that is, EV-associated PLY produced by the D39 strain (EVs-D39) could induce the formation of LC3-associated monolayer vacuoles [LC3-associated phagocytosis (LAP)] and co-localize with the NADPH oxidase 2 (NOX2) complex but not ULK1 when macrophages were infected with the D39Δply strain. In addition, EV-associated PLY derived from the EVs-D39 promoted macrophages to release more reactive oxygen species (ROS) and expression of p-p70s6k than EV-associated PLY derived from the D39ΔhsdSA strain (EVs-D39ΔhsdSA ), whereas the expression of p-ULK1 was reversed, indicating that EVs-D39ΔhsdSA was more likely to induce conventional xenophagy. Furthermore, we identified the β1 integrin receptor as a crucial inducer of ROS to mediate LAP activation. Bacterial evasion of host clearance is closely related to insufficient acidification after the fusion of autophagosomes or LAPosomes with lysosomes. Of note, we found EV-associated PLY damaged the integrity of the lysosome membrane and changed the pH gradient, resulting in lysosomes being unable to remove intracellular bacteria and ultimately prolonging the survival of S. pneumoniae in macrophages. Finally, the extracted mouse alveolar macrophages and mouse intranasal infection models were employed to further verify the above findings. IMPORTANCE S. pneumoniae is a major human pathogen that undergoes a spontaneous and reversible phase variation that allows it to survive in different host environments. Interestingly, we found hsdSA , a gene that manipulated the phase variation, promoted the survival and replication of S. pneumoniae in macrophages by regulating EV production and EV-associated PLY. More importantly, here we provided the first evidence that higher EV-associated PLY (produced by D39) could form LAPosomes that were single membrane compartments containing S. pneumoniae, which are induced by integrin β1/NOX2/ROS pathway. At the same time, EV-associated PLY increased the permeability of lysosome membrane and induced an insufficient acidification to escape the host killing, and ultimately prolonged the survival of S. pneumoniae in macrophages. In contrast, lower EV-associated PLY (produced by D39ΔhsdSA ) activated ULK1 recruitment to form double-layered autophagosomes to eliminate bacteria.

Introduction and backgroundIntimate partner violence (IPV) and child malnutrition are global public health issues. Assessing the association between IPV and child anthropometric failures (stunting, underweight, and wasting) in 29 Sub-Saharan African (SSA) countries can provide significant global health solutions. Some studies have found an association between IPV against women and child malnutrition, but the conclusions are inconsistent. The physical and psychological conditions, living environment, and rights of the mother may be involved.MethodsWe collected and analyzed the Demographic and Health Surveys data (2010–2021) of 29 SSA countries. The main exposure variables were various types of IPV, classified as physical, sexual, and emotional violence. The outcome was the child’s development index, which can be roughly divided into stunting, wasting, and underweight. An adjusted binary logistic regression model was used to test the relationship between IPV and children’s nutritional status.ResultsA total of 186,138 children under 5 years of age were included in the analysis; 50,113 (27.1%) of the children were stunted, 11,329 (6.1%) were wasted, and 39,459 (21.3%) were underweight in all regions. The child’s gender, age, duration of breastfeeding, complementary feeding, and vitamin A supplements intake in the past 6 months were associated with their nutritional status (p 0.05).ConclusionIPV is positively associated with child stunting in SSA countries. Sexual violence showed a strong positive correlation with stunting. Wasting was unexpectedly negatively associated with IPV. There was no clear correlation between underweight and violence.

Abstract The carbon stock function of harvested wood products (HWPs) is attracting attention among climate change countermeasures. Among HWPs, particle board (PB) and fiberboard (FB) mainly use recycled materials. This study estimated carbon stocks of PB and FB and their annual changes over the past 70 years in Japan using three methods of the Intergovernmental Panel on Climate Change guidelines: Tiers 1–3. Tier 1 uses first order decay (FOD), a 25-year half-life, and the Food and Agriculture Organization of the United Nations database. Tier 2 uses FOD, a 25-year half-life, and Japan-specific statistics. Tier 3 uses a log-normal distribution for the decay function and a 38–63-year half-life of building PB/FB. Japan’s PB and FB carbon stocks have increased for the past 70 years. The latest carbon stock in early 2022 and the annual change in carbon stock in 2021 was 21.83 million t-C and 0.42 million t-C/year, respectively for Tier 3. Tier 3 has the highest estimation accuracy by using decay functions and half-lives that match the actual conditions of building PB and FB, whereas Tiers 1 and 2 were underestimates. Approximately 40% of the carbon stock is derived from waste wood, which extends its utilization.

Highlights A novel strategy was developed to construct ultrathin microfiber composite hydrogel films (< 5 μm) by embedding an electrospun fiber network into a hydrogel. The microfiber composite hydrogel offers tunable modulus in a broad range (from ~ 5 kPa to tens of MPa), which matches the modulus of most biological tissues and organs. The ultrathin configuration and ultrasoft nature allow the microfiber composite hydrogel seamlessly attaching to various rough surfaces.

Programmed death-ligand 1 (PD-L1), expressed on the surface of tumor cells, can bind to programmed cell death-1 (PD-1) on T cells. The interaction of PD-1 and PD-L1 can inhibit T-cell responses by decreasing T-cell activity and accelerating their apoptosis. Various cancers express high levels of PD-L1 and exploit PD-L1/PD-1 signaling to evade T-cell immunity, and immunotherapies targeting the PD-1/PD-L1 axis have been shown to exert remarkable anti-tumor effects; however, not all tumor patients benefit from these therapies. Therefore, study of the mechanisms regulating PD-L1 expression are imperative. In this review, we explore regulation of PD-L1 expression in the contexts of gene transcription, signaling pathways, histone modification and remodeling, microRNAs, long noncoding RNAs, and post-translational modification. Current developments in studies of agents that block PD-L1 and correlations between immunotherapies targeting PD-1/PD-L1 and PD-L1 expression are also summarized. Our review will assist in understanding of PD-L1 expression regulation and discusses the implications of reported findings in cancer diagnosis and immunotherapy.

Background: Nanoparticles conjugated with fluorescent probes have versatile applications, serving not only for targeted fluorescent imaging but also for evaluating the in vivo profiles of designed nanoparticles. However, the relationship between fluorophore density and nanoparticle behavior remains unexplored. Methods: The IR783-modified liposomes (IR783-sLip) were prepared through a modified ethanol injection and extrusion method. The cellular uptake efficiency of IR783-sLip was characterized by flow cytometry and fluorescence microscope imaging. The effects of IR783 density on liposomal in vivo behavior were investigated by pharmacokinetic studies, biodistribution studies, and in vivo imaging. The constitution of protein corona was analyzed by the Western blot assay. Results: Dense IR783 modification improved cellular uptake of liposomes in vitro but hindered their blood retention and tumor imaging performance in vivo. We found a correlation between IR783 density and protein corona absorption, particularly IgM, which significantly impacted the liposome performance. Meanwhile, we observed that increasing IR783 density did not consistently improve the effectiveness of tumor imaging. Conclusions: Increasing the density of modified IR783 on liposomes is not always beneficial for tumor near-infrared (NIR) imaging yield. It is not advisable to prematurely evaluate novel nanomaterials through fluorescence dye conjugation without carefully optimizing the density of the modifications.

PurposeTOPBP1 interacting checkpoint and replication regulator (TICRR), a hub gene of the Cdk2-mediated initiation step of DNA replication, has been shown an essential role in tumorigenesis by accelerating the DNA replication of tumor cells.MethodsRT-qPCR was used to detect the mRNA expression of TICRR in LUAD tumors and adjacent normal tissues. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database of LUAD were acquired to analyze the critical role of TICRR expression in survival prognosis and clinicopathology characters in LUAD. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) were performed using the R package. The correlation of TICRR expression with immune cell infiltration, RNA epigenetic modification, DNA damage repair (DDR) pathway, and cell metabolism of LUAD was further explored to verify significant conclusions.ResultsTICRR was significantly upregulated in most cancer types, including LUAD, lung squamous cell carcinoma (LUSC), and others. Cox regression analysis indicated the overexpression of TICRR was associated with poor survival in several cancers. In LUAD, TICRR expression was positively correlated with tumor stage and was increased in smoking, male, and high tumor mutational burden (TMB) patients. Enrichment analysis revealed that TICRR could influence tumor proliferation and prognosis via activating pathways involving cell cycle, DNA repair, DNA replication, cysteine metabolism, oxidative phosphorylation, and ubiquitin-mediated proteolysis pathways. Interestingly, high TICRR expression correlated with DDR pathway signature (34 genes), 37 m6A/m5C regulated genes, and some metabolism-regulated genes. Silencing the TICRR gene affects cysteine metabolism and modifies cancer-related pathways, with decreased cell cycle and increased B/T cell receptor signaling. Our TICRR risk model accurately predicts LUAD patient prognosis, validated across GEO datasets, and is integrated with clinical characteristics via a nomogram, facilitating personalized treatment strategies and enhancing patient management.ConclusionsTaken together, TICRR has emerged as a promising prognostic biomarker in lung adenocarcinoma (LUAD), with implications in immune activation, cell cycle regulation, RNA modification, and tumor energy metabolism. These findings suggest that TICRR could serve as a viable therapeutic target and a reliable prognostic indicator for LUAD.

BackgroundColorectal cancer (CRC) is a prevalent malignancy with diverse molecular characteristics. The NGS-based approach enhances our comprehension of genomic landscape of CRC and may guide future advancements in precision oncology for CRC patients.MethodIn this research, we conducted an analysis using Next-Generation Sequencing (NGS) on samples collected from 111 individuals who had been diagnosed with CRC. We identified somatic and germline mutations and structural variants across the tumor genomes through comprehensive genomic profiling. Furthermore, we investigated the landscape of driver mutations and their potential clinical implications.ResultsOur findings underscore the intricate heterogeneity of genetic alterations within CRC. Notably, BRAF, ARID2, KMT2C, and GNAQ were associated with CRC prognosis. Patients harboring BRAF, ARID2, or KMT2C mutations exhibited shorter progression-free survival (PFS), whereas those with BRAF, ARID2, or GNAQ mutations experienced worse overall survival (OS). We unveiled 80 co-occurring and three mutually exclusive significant gene pairs, enriched primarily in pathways such as TP53, HIPPO, RTK/RAS, NOTCH, WNT, TGF-Beta, MYC, and PI3K. Notably, co-mutations of BRAF/ALK, BRAF/NOTCH2, BRAF/CREBBP, and BRAF/FAT1 correlated with worse PFS. Furthermore, germline AR mutations were identified in 37 (33.33%) CRC patients, and carriers of these variants displayed diminished PFS and OS. Decreased AR protein expression was observed in cases with AR germline mutations. A four-gene mutation signature was established, incorporating the aforementioned prognostic genes, which emerged as an independent prognostic determinant in CRC via univariate and multivariate Cox regression analyses. Noteworthy BRAF and ARID2 protein expression decreases detected in patients with their respective mutations.ConclusionThe integration of our analyses furnishes crucial insights into CRC’s molecular characteristics, drug responsiveness, and the construction of a four-gene mutation signature for predicting CRC prognosis.

Two experiments were conducted in this research. Experiment 1 investigated the spatial expression characteristics of calcium (Ca) and phosphorus (P) transporters in the duodenum, jejunum, and ileum of 21-day-old broilers provided with adequate nutrient feed. Experiment 2 evaluated the effects of dietary vitamin D3 (VD3) concentration (0, 125, 250, 500, 1,000, and 2,000 IU/kg) on growth performance, bone development, and gene expression levels of intestinal Ca and P transporters in 1–21-day-old broilers provided with the negative control diet without supplemental VD3. Results in experiment 1 showed that the mRNA levels of calcium-binding protein 28-kDa (CaBP-D28k), sodium-calcium exchanger 1 (NCX1), plasma membrane calcium ATPase 1b (PMCA1b), and IIb sodium-phosphate cotransporter (NaPi-IIb) were the highest in the broiler duodenum. By contrast, the mRNA levels of inorganic phosphate transporter 1 (PiT-1) and 2 (PiT-2) were the highest in the ileum. Results in experiment 2 showed that adding 125 IU/kg VD3 increased body weight gain (BWG), feed intake (FI), bone weight, and percentage and weight of Ca and P in the tibia and femur of 1–21-day-old broilers compared with the negative control diet (p < 0.05). The rise in dietary VD3 levels from 125 to 1,000 IU/kg further increased the BWG, FI, and weights of the bone, ash, Ca, and P (p < 0.05). No difference in growth rate and leg bone quality was noted in the broilers provided with 1,000 and 2,000 IU/kg VD3 (p > 0.05). Supplementation with 125–2,000 IU/kg VD3 increased the mRNA abundances of intestinal Ca and P transporters to varying degrees. The mRNA level of CaBP-D28k increased by 536, 1,161, and 28 folds in the duodenum, jejunum, and ileum, respectively, after adding 1,000 IU/kg VD3. The mRNA levels of other Ca and P transporters (PMCA1b, NCX1, NaPi-IIb, PiT-1, and PiT-2) increased by 0.57–1.74 folds by adding 1,000–2,000 IU/kg VD3. These data suggest that intestinal Ca and P transporters are mainly expressed in the duodenum of broilers. Moreover, the addition of VD3 stimulates the two mineral transporter transcription in broiler intestines.

Abstract Background Pre-eclampsia (PE) is one of the leading causes of maternal and fetal morbidity/mortality during pregnancy, and alpha-2-macroglobulin (A2M) is associated with inflammatory signaling; however, the pathophysiological mechanism by which A2M is involved in PE development is not yet understood. Methods Human placenta samples, serum, and corresponding clinical data of the participants were collected to study the pathophysiologic mechanism underlying PE. Pregnant Sprague–Dawley rats were intravenously injected with an adenovirus vector carrying A2M via the tail vein on gestational day (GD) 8.5. Human umbilical artery smooth muscle cells (HUASMCs), human umbilical vein endothelial cells (HUVECs), and HTR-8/SVneo cells were transfected with A2M-expressing adenovirus vectors. Results In this study, we demonstrated that A2M levels were significantly increased in PE patient serum, uterine spiral arteries, and feto-placental vasculature. The A2M-overexpression rat model closely mimicked the characteristics of PE (i.e., hypertension in mid-to-late gestation, histological and ultrastructural signs of renal damage, proteinuria, and fetal growth restriction). Compared to the normal group, A2M overexpression significantly enhanced uterine artery vascular resistance and impaired uterine spiral artery remodeling in both pregnant women with early-onset PE and in pregnant rats. We found that A2M overexpression was positively associated with HUASMC proliferation and negatively correlated with cell apoptosis. In addition, the results demonstrated that transforming growth factor beta 1 (TGFβ1) signaling regulated the effects of A2M on vascular muscle cell proliferation described above. Meanwhile, A2M overexpression regressed rat placental vascularization and reduced the expression of angiogenesis-related genes. In addition, A2M overexpression reduced HUVEC migration, filopodia number/length, and tube formation. Furthermore, HIF-1α expression was positively related to A2M, and the secretion of sFLT-1 and PIGF of placental origin was closely related to PE during pregnancy or A2M overexpression in rats. Conclusions Our data showed that gestational A2M overexpression can be considered a contributing factor leading to PE, causing detective uterine spiral artery remodeling and aberrant placental vascularization.

Model-Based Reinforcement Learning (MBRL) has been gradually applied in the field of Robot Learning due to its excellent sample efficiency and asymptotic performance. However, for high-dimensional learning tasks in complex scenes, the exploration and stable training capabilities of the robot still need enhancement. In light of policy planning and policy optimization, we propose a bidirectional model-based policy optimization algorithm based on adaptive gaussian noise and improved confidence weights (BMPO-NW). The algorithm parameterizes bidirectional policy networks into noise networks by adding different adaptive Gaussian noises to the connection weights and biases. This can improve the randomness of policy search and induce efficient exploration for the robot. Simultaneously, the confidence weight of improved activation function is introduced into the Q-function update formula of SAC, which can reduce the error propagation problem of target Q-network, and enhance the robot’s training stability. Finally, we implement the improved algorithm based on the framework of bidirectional model-based policy optimization algorithm (BMPO) to ensure asymptotic performance and sample efficiency. Experimental results in MuJoCo benchmark environments demonstrate that the learning speed of BMPO-NW is about 20% higher than baseline methods, the average reward is about 15% higher than other MBRL methods, and 50%-70% higher than MFRL methods, while the training process is more stable. Ablation experiments and different variant design experiments further verify the feasibility and robustness. The research results provide theoretical support for the conclusion of this paper and hold significant practical value for MBRL to help the robot realize applications in complex scenarios.

Objective This research aimed to evaluate the effects of age on growth, tibia development, and intestinal calcium (Ca) and phosphorus (P) transporter gene expressions in broiler chickens. Methods A total of 224 male Arbor Acres broilers were fed with nutrient-adequate diets and reared in eight cages (28 broilers per cage). Eight broilers (one broiler per cage) were selected and killed at 5, 10, 15, 20, 25, 30, 35, and 40 days of age, respectively. Results Body weight continuously increased with age of broiler chickens from 5 to 40 days. The bone weight, ash weight, diameter, and length of the tibia also increased with broiler age. By contrast, the tibia ash, Ca, and P percentages quadratically changed with age (p

Abstract Background Glaucoma, the major cause of irreversible blindness worldwide, is characterized by progressive degeneration of retinal ganglion cells (RGCs). Current treatments for glaucoma only slow or partially prevent the disease progression, failing to prevent RGCs death and visual field defects completely. Glutamate excitotoxicity via N-methyl-d-aspartic acid (NMDA) receptors plays a vital role in RGCs death in glaucoma, which is often accompanied by oxidative stress and NLRP3 inflammasome activation. However, the exact mechanisms remain unclear. Methods The glutamate-induced R28 cell excitotoxicity model and NMDA-induced mouse glaucoma model were established in this study. Cell counting kit-8, Hoechst 33342/PI dual staining and lactate dehydrogenase release assay were performed to evaluate cell viability. Annexin V-FITC/PI double staining was used to detect apoptosis and necrosis rate. Reactive oxygen species (ROS) and glutathione (GSH) were used to detect oxidative stress in R28 cells. Levels of proinflammatory cytokines were measured by qRT-PCR. Transmission electron microscopy (TEM) was used to detect necroptotic morphological changes in RGCs. Retinal RGCs numbers were detected by immunofluorescence. Hematoxylin and eosin staining was used to detect retinal morphological changes. The expression levels of RIP1, RIP3, MLKL and NLRP3 inflammasome-related proteins were measured by immunofluorescence and western blotting. Results We found that glutamate excitotoxicity induced necroptosis in RGCs through activation of the RIP1/RIP3/MLKL pathway in vivo and in vitro. Administration of the RIP3 inhibitor GSK872 and RIP1 inhibitor necrostatin-1 (Nec-1) prevented glutamate-induced RGCs loss, retinal damage, neuroinflammation, overproduction of ROS and a decrease in GSH. Furthermore, after suppression of the RIP1/RIP3/MLKL pathway by GSK872 and Nec-1, glutamate-induced upregulation of key proteins involved in NLRP3 inflammasome activation, including NLRP3, pro-caspase-1, cleaved-caspase-1, and interleukin-1β (IL-1β), was markedly inhibited. Conclusions Our findings suggest that the RIP1/RIP3/MLKL pathway mediates necroptosis of RGCs and regulates NLRP3 inflammasome activation induced by glutamate excitotoxicity. Moreover, GSK872 and Nec-1 can protect RGCs from necroptosis and suppress NLRP3 inflammasome activation through inhibition of RIP1/RIP3/MLKL pathway, conferring a novel neuroprotective treatment for glaucoma.

Background: Pediatric gliomas (PGs) are highly aggressive and predominantly occur in young children. In pediatric gliomas, abnormal expression of Homeobox (HOX) family genes (HFGs) has been observed and is associated with the development and progression of the disease. Studies have found that overexpression or underexpression of certain HOX genes is linked to the occurrence and prognosis of gliomas. This aberrant expression may contribute to the dysregulation of important pathological processes such as cell proliferation, differentiation, and metastasis. This study aimed to propose a novel HOX-related signature to predict patients’ prognosis and immune infiltrate characteristics in PGs.Methods: The data of PGs obtained from publicly available databases were utilized to reveal the relationship among abnormal expression of HOX family genes (HFGs), prognosis, tumor immune infiltration, clinical features, and genomic features in PGs. The HFGs were utilized to identify heterogeneous subtypes using consensus clustering. Then random forest-supervised classification algorithm and nearest shrunken centroid algorithm were performed to develop a prognostic signature in the training set. Finally, the signature was validated in an internal testing set and an external independent cohort.Results: Firstly, we identified HFGs significantly differentially expressed in PGs compared to normal tissues. The individuals with PGs were then divided into two heterogeneous subtypes (HOX-SI and HOX-SII) based on HFGs expression profiles. HOX-SII showed higher total mutation counts, lower immune infiltration, and worse prognosis than HOX-SI. Then, we constructed a HOX-related gene signature (including HOXA6, HOXC4, HOXC5, HOXC6, and HOXA-AS3) based on the cluster for subtype prediction utilizing random forest supervised classification and nearest shrunken centroid algorithm. The signature was revealed to be an independent prognostic factor for patients with PGs by multivariable Cox regression analysis.Conclusion: Our study provides a novel method for the prognosis classification of PGs. The findings also suggest that the HOX-related signature is a new biomarker for the diagnosis and prognosis of patients with PGs, allowing for more accurate survival prediction.

Vaccines are one of the most effective means of preventing influenza A, typically containing the hemagglutinin (HA) of the influenza A virus. However, antigenic drift and shift of the influenza A virus can lead to instability in vaccine efficacy. Compared to HA, the antigenic variation rate of neuraminidase (NA) is slower. In traditional inactivated influenza vaccines, although they contain a certain amount of NA, there are significant differences between different batches, which cannot consistently induce NA-based immune responses. Therefore, NA is often overlooked in vaccine development. In this study, we report an mRNA vaccine encoding the NA of two strains of influenza A virus. The experimental results demonstrated that when matched with the viral strain, this mRNA vaccine induced high levels of neutralizing antibodies, providing a protective effect to mice in viral challenge experiments, and this immune response was shown to be biased towards the Th1 type. In summary, this study demonstrates that NA is a promising potential antigen, providing new insights for the development of influenza A virus vaccines.

Bacterial wilt is a significant soil-borne disease that poses a threat to mulberry production yield and quality of agricultural production worldwide. However, the disease resistance mechanisms dependent on root exudates are not well understood. In this present study, we investigated the antibacterial mechanisms of the main active substances (erucamide, oleamide, and camphor bromide) present in mulberry root exudates (MRE) against Ralstonia pseudosolanacearum (Rp), the causal agent of bacterial wilt. Our findings revealed that these three active substances inhibited the growth activity of Rp by affecting the cell morphology and extracellular polysaccharide content, as well as triggering a burst of reactive oxygen species. The active substances induced oxidative stress, leading to a decrease in Rp growth. Additionally, the expression levels of key genes in the hrp gene cluster (hrpB, hrpX, and hrpF) and other virulence-related genes (such as ripAW, ripAE, Rs5-4819, Rs5-4374, ace, egl3, and pehB) were significantly reduced upon treatment with the active substances. Further pathogenicity experiments demonstrated that root exudates (at a concentration of 1.5 mg·mL−1) delayed or slowed down the occurrence of bacterial wilt in mulberry. These findings provide valuable insight into the antimicrobial mechanisms of MRE against Rp and lay a theoretical foundation for the development and application of biocontrol agents to control mulberry bacterial wilt.

Abstract Spiking Neural Network is known as the third‐generation artificial neural network whose development has great potential. With the help of Spike Layer Error Reassignment in Time for error back‐propagation, this work presents a new network called SpikeGoogle, which is implemented with GoogLeNet‐like inception module. In this inception module, different convolution kernels and max‐pooling layer are included to capture deep features across diverse scales. Experiment results on small NMNIST dataset verify the results of the authors’ proposed SpikeGoogle, which outperforms the previous Spiking Convolutional Neural Network method by a large margin.

In the field of water depth inversion using imagery, the commonly used methods are based on water reflectance and wave extraction. Among these methods, the Optical Bathymetry Method (OBM) is significantly influenced by bottom sediment and climate, while the wave method requires a specific study area. This study introduces a method combining the FFT and spatial profile measurement to invert the wavelength of the wave bathymetry method (WBM), which enhances accuracy and reduces workload. The method was applied to remote sensing images of Sanya Bay in China, obtained from the Worldview satellite. The average error of the inverted depth results after applying the wavelength inversion technique was 15.9%, demonstrating consistency with the depth measurements obtained through the OBM in clear water of the bay. The WBM has notable advantages over the OBM, as it is unaffected by water quality. In addition, the influence of wave period on the accuracy of water depth retrieval was theoretically evaluated, revealing that a larger wave period leads to a better depth measurement. The depth measurement from two images with different wave periods aligned with the theoretical analysis. These results showcase the applicability and potential of the WBM for accurately estimating water depth in various coastal environments.

Accurate energy consumption model is the basis of energy saving optimal control of air conditioning system. The existing energy consumption model of air conditioning water system mainly focuses on a certain equipment or a part of the cycle. However, the coupling between water system equipment will affect the setting of optimal energy consumption of equipment. It is necessary to establish the energy consumption model of water system as a whole. However, air conditioning water system is a highly nonlinear complex system, and its precise physical model is difficult to establish. The main goal of this paper is to develop an accurate machine learning modeling and optimization technique to predict the total energy consumption of air conditioning water system by using the actual operation data collected. The main contributions of this work are as follows: (1) Three commonly used machine learning techniques, artificial neural network (ANN), support vector machine (SVM) and classification regression tree (CART), are used to build prediction models of air conditioning water system energy consumption. The results show that all the three models have fast training speed, but the ANN model has better performance in cross-validation. (2) The improved differential evolution algorithm was used to optimize the parameters (initial weights and thresholds) of the ANN, which solved the problem that the ANN is easy to fall into the local optimal solution. The simulation results show that the root mean square error (RMSE) of the improved model decreases by 20.5%, the mean absolute error (MAE) decreases by 30.2%, and the coefficient of determination (R2) increases from 0.9227 to 0.9512. (3) Sensitivity analysis of the established optimization model shows that chilled water flow, chilled water outlet temperature and air conditioning load are the main factors affecting the total energy consumption.

Abstract Metastasis is the most important reason for the poor prognosis of gastric cancer (GC) patients, and the mechanism urgently needs to be clarified. Here, we explored a prognostic model for the estimation of tumor-associated mortality in GC patients and revealed the RNA-binding protein RBMS1 as a candidate promoter gene for GC metastasis by analyzing GOBO and Oncomine high-throughput sequencing datasets for 408 GC patients. Additionally, RBMS1 was observed with overexpression in 85 GC patient clinical specimens by IHC staining and further be verified its role in GC metastasis via inducing EMT process both in in vitro and in vivo experiments. Moreover, we identified that IL-6 was predicted to be one of the most significant upstream cytokines in the RBMS1 overexpression gene set based on the Ingenuity Pathway Analysis (IPA) algorithm. Most importantly, we also revealed that RBMS1 could promote migration and invasion through IL6 transactivation and JAK2/STAT3 downstream signaling pathway activation by influencing histone modification in the promoter regions after binding with the transcription factor MYC in the HGC-27 and SGC-7901 GC cell lines. Hence, we shed light on the potential molecular mechanisms of RBMS1 in the promotion of GC metastasis, which suggests that RBMS1 may be a potential therapeutic target for GC patients.

The authors demonstrate enhanced hydrovoltaic power generation using heat conduction effects to break through the slow heat replenishment limit common in evaporation-induced hydrovoltaic generators.

Background Research into neural mechanisms underlying cue-induced cigarette craving has attracted considerable attention for its significant role in treatments. However, there is little understanding about the effects of exposure to smoking-related cues on electroencephalogram (EEG) microstates of smokers, which can reflect abnormal brain network activity in several psychiatric disorders. Aims To explore whether abnormal brain network activity in smokers on exposure to smoking-related cues would be captured by EEG microstates. Method Forty smokers were exposed to smoking and neutral imagery conditions (cues) during EEG recording. Behavioural data and parameters for microstate topographies associated with the auditory (A), visual (B), salience and memory (C) and dorsal attention networks (D) were compared between conditions. Correlations between microstate parameters and cigarette craving as well as nicotine addiction characteristics were also analysed. Results The smoking condition elicited a significant increase in the duration of microstate classes B and C and in the duration and contribution of class D compared with the neutral condition. A significant positive correlation between the increased duration of class C (smoking minus neutral) and increased craving ratings was observed, which was fully mediated by increased posterior alpha power. The increased duration and contribution of class D were both positively correlated with years of smoking. Conclusions Our results indicate that smokers showed abnormal EEG microstates when exposed to smoking-related cues compared with neutral cues. Importantly, microstate class C (duration) might be a biomarker of cue-induced cigarette craving, and class D (duration and contribution) might reflect the relationship between cue-elicited activation of the dorsal attention network and years of smoking.

Abstract Solar‐driven vapor generation technology can directly produce clean water, but existing strategies remain challenging in achieving both high evaporation performance and good salt resistance due to complex water‐thermal management. Here, we constructed hydrogel‐based hierarchically nanostructured evaporator (HNE) with vertically aligned micro water transportation pathways and water confined ion selective nanochannels. Based on the polarity modified hierarchical structures and umbrella‐shaped geometry design, HNEs can achieve high‐speed water transfer at low saturated water content to realize efficient heat energy confinement, and provide more heat exchange sites. Consequently, an exciting water evaporation rate of 3.68 kg m−2 h−1 and the efficiency of 91.1% were achieved under 1 sun solar radiation. More importantly, the overlapping electrical double layer in the narrow nanochannels endows the ions selectivity of the nanochannel to reject anions, resulting in reliable long‐term salt resistance. The ingenious design was creatively confirmed by streaming potential and validated during long‐term efficient work.

Background: Prostate cancer (PCa) is the second most common cancer among men worldwide. Perineural invasion (PNI) was a prominent characteristic of PCa, which was recognized as a key factor in promoting PCa progression. As a complex and heterogeneous disease, its true condition is difficult to explain thoroughly with conventional bulk RNA sequencing. Thus, an improved understanding of PNI-PCa progression at the single-cell level is needed.Methods: In this study, we performed scRNAseq on tumor tissues of three PNI-PCa patients. Principal component analysis (PCA) and Uniform manifold approximation and projection (UMAP) were used to reduce dimensionality and visualize the cellular composition of tumor tissues. The differently expressed genes among each cluster were identified by EdgeR. GO enrichment analysis was used to understand the roles of genes within the clusters. Pseudotime cell trajectory was used to reveal the molecular pathways underlying cell fate decisions and identify genes whose expression changed as the cells underwent transition. We applied CellPhoneDB to identify cell-cell interactions among the epithelial and neural cells in PNI-PCa.Results: Analysis of the ∼17,000 single-cell transcriptomes in three PNI prostate cancer tissues, we identified 12 major cell clusters, including neural cells and two epithelial subtypes with different expression profiles. We found that basal/intermediate epithelial cell subtypes highly expressed PCa progression-related genes, including PIGR, MMP7, and AGR2. Pseudotime trajectory analysis showed that luminal epithelial cells could be the initiating cells and transition to based/intermediate cells. Gene ontology (GO) enrichment analysis showed that pathways related to cancer progressions, such as lipid catabolic and fatty acid metabolic processes, were significantly enriched in basal/intermediate cells. Our analysis also suggested that basal/intermediate cells communicate closely with neural cells played a potential role in PNI-PCa progression.Conclusion: These results provide our understanding of PNI-PCa cellular heterogeneity and characterize the potential role of basal/intermediate cells in the PNI-PCa progression.

The proteomic analysis from samples of patients with preeclampsia (PE) displayed a low level of ferritin light chains (FTL), but we do not know what the significance of reduced FTL in PE pathophysiology is. To address this question, we first demonstrated that FTL was expressed in first- and third-trimester cytotrophoblasts, including extravillous trophoblasts (EVTs), of the human placenta. Furthermore, a pregnant rat model of FTL knockdown was successfully established by intravenously injecting adenoviruses expressing shRNA targeting FTL. In pregnant rats with downregulated FTL, we observed PE-like phenotypes and impaired spiral arterial remodelling, implying a causal relationship between FTL downregulation and PE. Blocking ferroptosis with ferrostatin-1 (Fer-1) significantly rescued the above PE-like phenotypes in pregnant rats with FTL knockdown. Furthermore, using trophoblast cell line and chorionic villous explant culture assays, we showed that FTL downregulation induced cell death, especially ferroptosis, resulting in defective uterine spiral artery remodelling. Eventually, this conclusion from the animal model was verified in PE patients’ placental tissues. Taken together, this study revealed for the first time that FTL reduction during pregnancy triggered ferroptosis and then caused defective uterine spiral artery remodelling, thereby leading to PE.

BackgroundWe aimed to investigate the effects of blood lipids and lipid-lowering agents on osteoarthritis (OA) risk.Materials and methodsWe performed Mendelian randomization (MR) analyses to estimate the causal effect of blood low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels on knee and hip OA. Single nucleotide polymorphisms (SNPs) were selected from large genome-wide association studies (GWASs) of individuals of European ancestry as genetic instruments for blood lipid levels. The associations of selected genetic instruments with knee and hip OA were estimated in a recent GWAS of the UK Biobank and arcOGEN datasets. Univariate and multivariate MR analyses were performed to detect and adjust for potential pleiotropy. Furthermore, genetic instruments in HMGCR, NPC1L1, and PCSK9 regions were used to mimic LDL-C-lowering effects of statin, ezetimibe, and evolocumab, respectively.ResultsGenetically determined LDL-C increments led to reduced risks of both knee OA (OR = 0.91 per 1-SD increment, 95% CI: 0.86–0.95, P = 6.3 × 10−5) and hip OA (OR = 0.92, 95% CI: 0.85–0.99, P = 0.027). Multivariate MR analysis proved that the effect was independent of HDL-C, TG, and body mass index. TG increment was associated with reduced risks of hip OA in the univariate MR analysis; however, this was not supported by the multivariate MR analysis. Genetically proxied LDL-C-lowering effects of statins are related to increased risks of knee OA but not hip OA.ConclusionsThe findings suggested that LDL-C increments have independent protective effects on both knee and hip OA. LDL-C-lowering effects of statins may increase the risk of knee OA.

The Qilian Mountains (QMs) act as the “water tower” of the Hexi Corridors, playing an important role in the regional ecosystem security and economic development. Therefore, it is of great significance to understand the spatiotemporal characteristics of precipitation in the QMs. This study evaluated the performance of 21 models of phase 6 of the Coupled Model Intercomparison Project (CMIP6) from 1959 to 1988 based on ERA5 and in situ datasets. In addition, the precipitation changing trend from 2015 to 2100 was projected according to four shared socioeconomic pathways (SSPs): namely, SSP126, SSP245, SSP370, and SSP585. The results have shown the following: (1) all CMIP6 models could reflect the same precipitation changing trend, based on the observed datasets (−2.01 mm·10a−1), which was slightly lower than that of ERA5 (2.82 mm·10a−1). Multi-mode ensemble averaging (MME) showed that the projected precipitation-change trend of the four scenarios was 5.73, 9.15, 12.23, and 16.14 mm·10a−1, respectively. (2) The MME and ERA5 showed the same precipitation spatial pattern. Also, during the period 1959–1988, the MME in spring, summer, autumn and winter was 130.07, 224.62, 95.96, and 29.07 mm, respectively, and that of ERA5 was 98.57, 280.77, 96.85, and 22.64 mm, respectively. The largest precipitation difference in summer was because of strong convection and variable circulation. (3) From 2015 to 2100, the snow-to-rain ratio was between 0.1 and 1.1, and the snow-to-rain ratio climate tendency rate was concentrated in the range of −10~0.1 mm·10a−1. Both of these passed the significance test (p < 0.05). The projected rainfall of all four SSPs all showed an increasing trend with values of 6.20, 11.31, 5.64, and 20.41 mm·10a−1, respectively. The snowfall of the four SSPs all showed a decreasing trend with values of 0.42, 2.18, 3.34, and 4.17 mm·10a−1, respectively.

With global warming, Arctic sea ice, as one of the important factors regulating climate, has put forward new requirements for research. At present, the ground penetrating radar (GPR) is a powerful tool to obtain the structure of Arctic sea ice. Traditional offset imaging techniques no longer meet research requirements, and the two-parameter full waveform inversion (FWI) method has received widespread attention. To solve the high nonlinearity and ill-posed problem of FWI, the L-BFGS optimization algorithm and Wolfe criterion of inexact line search were used to update the model. The parameter scale factor, multiscale inversion strategy, and total variation (TV) regularization were introduced to optimize the inversion results. Finally, the inversion of anomalous bodies with different scales and different physical parameters is carried out, which verifies the reliability of the proposed method for dual-parameter imaging of Arctic sea ice and provides a powerful tool for the study of Arctic sea ice.

Abstract Background PCV3 is a pathogen associated with porcine dermatitis and nephropathy syndrome (PDNS)-like clinical signs, reproductive failure, and cardiac and multiorgan inflammation, which was newly identified in 2016 in sows in USA. Recently, PCV3 has also been identified from several non-porcine species like (cattle, dog, wild boar, deer, mice and ticks). However, PCV3 infection in donkey is not well established. Since 2019, 300 blood samples were collected from female donkey, which was characterized by abortion and sterility, in Liaocheng city of China. Results In the present study, an investigation of PCV3 in donkey blood samples was undertaken employing by real time PCR. Positive rates of PCV3 in donkeys reach to 21.0 %. In addition, one full-length PCV3 genome sequence was obtained, and it had a highest identity with porcine circovirus 3 PCV3/CN/Nanjing2017 strain and is clustered to PCV3a genotype based on ORF2 sequences. Conclusions This is the first report of detection of PCV3 from female donkeys presenting reproductive failure in large-scale donkey farms, China. In addition, the PCV3 strain identified in this study shared the closest relationship with those from porcine, suggesting that PCV3 may be transmitted from pigs to donkeys. Totally, PCV3 infection in donkey should be concerned although the association between it and reproductive failure are not better understood.

The aim of this work is the preliminary clinical validation and accuracy evaluation of our automatic algorithms in assessing progression fetal femur length (FL) in ultrasound images. To compare the random forest regression model with the SegNet model from the two aspects of accuracy and robustness. In this study, we proposed a traditional machine learning method to detect the endpoints of FL based on a random forest regression model. Deep learning methods based on SegNet were proposed for the automatic measurement method of FL, which utilized skeletonization processing and improvement of the full convolution network. Then the automatic measurement results of the two methods were evaluated quantitatively and qualitatively with the results marked by doctors. 436 ultrasonic fetal femur images were evaluated by the two methods above. Compared the results of the above three methods with doctor's manual annotations, the automatic measurement method of femur length based on the random forest regression model was 1.23 ± 4.66 mm and the method based on SegNet was 0.46 ± 2.82 mm. The indicator for evaluating distance was significantly lower than the previous literature. Measurement method based SegNet performed better in the case of femoral end adhesion, low contrast, and noise interference similar to the shape of the femur. The segNet-based method achieves promising performance compared with the random forest regression model, which can improve the examination accuracy and robustness of the measurement of fetal femur length in ultrasound images.

Abstract Background Tomato (Solanum lycopersicum) is one of the most important horticultural crops, with a marked preference for nitrate as an inorganic nitrogen source. The molecular mechanisms of nitrate uptake and assimilation are poorly understood in tomato. NIN-like proteins (NLPs) are conserved, plant-specific transcription factors that play crucial roles in nitrate signaling. Results In this study, genome-wide analysis identified six NLP members in tomato genome. These members were clustered into three clades in a phylogenetic tree. Comparative genomic analysis showed that SlNLP genes exhibited collinear relationships to NLPs in Arabidopsis, canola, maize and rice, and that the expansion of the SlNLP family mainly resulted from segmental duplications in the tomato genome. Tissue-specific expression analysis showed that one of the close homologs of AtNLP6/7, SlNLP3, was strongly expressed in roots during both the seedling and flowering stages, that SlNLP4 and SlNLP6 exhibited preferential expression in stems and leaves and that SlNLP6 was expressed at high levels in fruits. Furthermore, the nitrate uptake in tomato roots and the expression patterns of SlNLP genes were measured under nitrogen deficiency and nitrate resupply conditions. Four SlNLPs, SlNLP1, SlNLP2, SlNLP4 and SlNLP6, were upregulated after nitrogen starvation. And SlNLP1 and SlNLP5 were induced rapidly and temporally by nitrate. Conclusions These results provide significant insights into the potential diverse functions of SlNLPs to regulate nitrate uptake.

The aging process leads to the gradual impairment of physiological functions in the elderly, making them more susceptible to the toxicity of environmental pollutants. In this study, aged zebrafish were first transplanted with the feces from young donors and subsequently exposed to perfluorobutanesulfonate (PFBS), an emerging persistent toxic pollutant. The interaction between young fecal transplant and PFBS inherent toxicity was investigated, focusing on reproductive performance and the underlying endocrine mechanism. The results showed that PFBS single exposure increased the percentage of primary oocytes in aged ovaries, implying a blockage of oogenesis. However, transplantation of young feces completely abolished the effects of PFBS and promoted oocyte growth, as inferred by the obviously lower percentage of primary oocytes, accompanied by a higher percentage of cortical-alveolar oocytes. Measurement of sex hormones found that PFBS significantly increased the blood concentration of estradiol and disrupted the balance of sex hormones in the elderly, which were, however, efficiently ameliorated by young fecal transplantation. Based on gene transcription along the hypothalamic-pituitary–gonadal axis, hierarchical clustering analysis showed similar profiles of the reproductive endocrine system between young zebrafish and their aged counterparts transplanted with young feces, implying that young fecal transplantation might refresh the endocrine system of aged recipients, regardless of PFBS exposure. The increased transcription levels of mRNAs encoding vitellogenin, activinBA, and membrane bound progestin receptors would cooperatively enhance the growth and maturation of oocytes in the ovaries of aged zebrafish receiving young fecal transplantation. Overall, the findings highlighted the potent efficacy of young fecal transplantation to improve the reproductive function of the elderly and to mitigate the endocrine disruption of an environmental pollutant. These findings are expected to broaden our understanding of the efficacy, mechanisms, and application of fecal transplantation.

Background: Preeclampsia (PE) is one of the leading causes of maternal and fetal morbidity and mortality worldwide. Placental oxidative stress has been identified as a major pathway to the development of PE. Ferroptosis is a new form of regulated cell death that is associated with iron metabolism and oxidative stress, and likely mediates PE pathogenesis. The aim of the study was to identify the key molecules involved in ferroptosis to further explore the mechanism of ferroptosis in PE.Methods: Gene expression data and clinical information were downloaded from the GEO database. The limma R package was used to screen differentially expressed genes (DEGs) and intersected with ferroptosis genes. The GO and KEGG pathways were then analyzed. Next, hub genes were identified via weighted gene co-expression network analysis (WGCNA). Receiver operating curves (ROCs) were performed for diagnostic and Pearson’s correlation of hub genes and clinicopathological characteristics. Immunohistochemistry and Western blot analysis were used to verify the expression of hub genes.Results: A total of 3,142 DEGs were identified and 30 ferroptosis-related DEGs were obtained. In addition, ferroptosis-related pathways were enriched by GO and KEGG using DEGs. Two critical modules and six hub genes that were highly related to diagnosis of PE were identified through WGCNA. The analysis of the clinicopathological features showed that NQO1 and SRXN1 were closely correlated with PE characteristics and diagnosis. Finally, Western blot and immunohistochemistry analysis confirmed that the expression of the SRXN1 protein in the placental tissue of patients with PE was significantly elevated, while the expression of NQO1 was significantly decreased.Conclusions: SRXN1 and NQO1 may be key ferroptosis-related proteins in the pathogenesis of PE. The study may provide a theoretical and experimental basis for revealing the pathogenesis of PE and improving the diagnosis of PE.

Objective: The aim of this study was to use machine learning methods to analyze all available clinical and laboratory data obtained during prenatal screening in early pregnancy to develop predictive models in preeclampsia (PE).Material and Methods: Data were collected by retrospective medical records review. This study used 5 machine learning algorithms to predict the PE: deep neural network (DNN), logistic regression (LR), support vector machine (SVM), decision tree (DT), and random forest (RF). Our model incorporated 18 variables including maternal characteristics, medical history, prenatal laboratory results, and ultrasound results. The area under the receiver operating curve (AUROC), calibration and discrimination were evaluated by cross-validation.Results: Compared with other prediction algorithms, the RF model showed the highest accuracy rate. The AUROC of RF model was 0.86 (95% CI 0.80–0.92), the accuracy was 0.74 (95% CI 0.74–0.75), the precision was 0.82 (95% CI 0.79–0.84), the recall rate was 0.42 (95% CI 0.41–0.44), and Brier score was 0.17 (95% CI 0.17–0.17).Conclusion: The machine learning method in our study automatically identified a set of important predictive features, and produced high predictive performance on the risk of PE from the early pregnancy information.

Perfluorobutanesulfonate (PFBS) is an environmental pollutant of emerging concern, which significantly impacts the metabolism and health of animals. Because of the loss of functional capacity, the aged animals are regarded more susceptible to the toxicity of environmental pollutants. In the present study, aged zebrafish were employed as the toxicological animal and transplanted with the feces collected from young donors for 14 days, after which the acclimated elderly were exposed to PFBS at environmentally relevant concentrations (0 and 100 μg/L) for another 14 days. When the exposure was concluded, glucose metabolic disturbances of PFBS in the aged and efficacy of young fecal transplant to mitigate the toxicity of PFBS were explored along the gut-liver axis. The results showed that PFBS exposure significantly inhibited the enzymatic activity of α-amylase in the gut, but increased the alanine aminotransferase (ALT) activity in the blood of the aged zebrafish, suggesting the impairment of intestinal digestive functions of carbohydrates and the induction of liver damage by PFBS. However, young fecal transplantation successfully ameliorated the toxicity of PFBS on α-amylase and ALT, underlining the benefits conveyed to the health of the elderly. In addition, transplantation of young feces was efficient to alleviate the hyperglycemia symptom in the elderly via stimulating the secretion of insulin. PFBS exposure increased blood glucagon level, disrupted insulin receptor transcription, and depleted hepatic glycogen store, which were all mitigated by young fecal transplant. Hepatic proteomic analysis also found dynamic interactions between young fecal transplantation and PFBS pollutant on the metabolic pathways of glucose and glycogen, involving glycolysis, gluconeogenesis, glycogenesis, and glycogenolysis. Overall, the present findings highlighted the beneficial effects of young fecal transplantation to protect the aged from the glucose metabolism toxicity of PFBS, thus providing a plausible measure to improve the health aging status.