Adaptive resistance of tumor cells to anti-vascular endothelial growth factor therapy: A reversible phenomenon.

Vascular endothelial growth factor (VEGF) inhibition is an essential targeted strategy for malignant tumors, but its efficacy is severely constrained by drug resistance. The traditional view holds that the target of VEGF inhibition is endothelial cells, and thus compensatory angiogenesis is considered the main mechanism of drug resistance. In this study, we found that tumor cells themselves could develop acquired resistance to VEGF therapy, indicating an independent resistance mechanism apart from angiogenesis. Notably, this acquired resistance was temporary, disappearing completely four days after discontinuing exposure to the drug in vitro. Our findings suggest that tumor cells may also be targets of VEGF inhibition, and their response to treatment should not be overlooked in contributing to drug resistance.

Impacts of Perioperative Comprehensive Nursing Intervention on Postoperative Urinary Incontinence and Quality of Life of Patients Undergoing Laparoscopic Radical Prostatectomy.

To evaluate the impact of perioperative comprehensive nursing intervention on postoperative urinary incontinence, various aspects of patient well-being were assessed. The comprehensive group, that received the nursing intervention, demonstrated significant improvements in self-care skills, health knowledge level, self-care responsibility, and self-concept compared to the standard group. The findings indicate that perioperative comprehensive nursing intervention has a remarkable effect on patients undergoing laparoscopic radical prostatectomy. This nursing intervention not only effectively improves postoperative urinary incontinence and alleviates negative emotions, such as anxiety and depression. Therefore, the implementation of this nursing intervention model is highly recommended for clinical practice and wider application.

The association between prenatal exposure to bisphenol A and offspring obesity: A systematic review.

In recent years, the global prevalence of childhood overweight and obesity has surged. Bisphenol A (BPA), prevalent in the manufacture of polycarbonate plastics and epoxy resins, is associated with this escalating obesity pattern. Both early life stages and pregnancy emerge as pivotal windows of vulnerability. This review systematically evaluates human studies to clarify the nexus between prenatal BPA exposure and offspring obesity. Our extensive literature search covered databases like PubMed, Web of Science, Cochrane Library, Embase, and Scopus, encompassing articles from their inception until July 2023. We utilized the Newcastle-Ottawa Scale (NOS) to evaluate the methodological rigor of the included studies, the Oxford Center for Evidence-Based Medicine Levels of Evidence Working Group (OCEBM) table to determine the level of the evidence, and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) guidelines to evaluate the certainty of the evidence with statistical significance. We centered on primary studies investigating the link between urinary BPA levels during pregnancy and offspring obesity. Our analysis included thirteen studies, with participant counts ranging from 173 to 1124 mother-child dyads. Among them, eight studies conclusively linked prenatal BPA exposure to increased obesity in offspring. Evaluation metrics for the effect of prenatal BPA on offspring obesity comprised BMI z-score, waist circumference, overweight/obesity classification, aggregate skinfold thickness, body fat percentage, and more. Present findings indicate that prenatal BPA exposure amplifies offspring obesity risk, with potential effect variations by age and gender. Therefore, further research is needed to explore the causal link between prenatal BPA exposure and obesity at different developmental stages and genders, and to elucidate the underlying mechanisms.

Bisphenol A exposure and thyroid dysfunction during pregnancy: A Systematic Review.

Bisphenol A (BPA) is a phenolic chemical that has been found to be associated with human health outcomes. It is one of the risk factors of thyroid function. Pregnancy is a vulnerable window for thyroid problems, because of the fluctuations in hormone levels. This review aimed to evaluate the association between BPA exposure and thyroid function during pregnancy. We conducted a comprehensive search of relevant databases, including PubMed, Scopus, Embase, Web of Science, and the Cochrane Library, for original studies published in English that reported data on BPA levels and thyroid-related hormone levels in pregnant women. We used the Newcastle-Ottawa Scale (NOS) to assess the methodological quality of the studies and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method to evaluate the quality of evidence. In total, 11 studies involving 6,526 individuals were included in this systematic review. These studies explored fluctuations in thyroid-related hormones, including TSH, TT3, TT4, FT3, and FT4 levels, as well as the TT4/TT3 and FT4/FT3 ratios. The systematic review is to evaluate the evidences between bisphenol A exposure and thyroid-related hormones in pregnant women. We found that BPA exposure in pregnancy might disturb the homeostasis of maternal thyroid-related hormones and suggest the increased risk of hyperthyroidism. Further studies based on the findings are required to explore the underlying mechanisms and determine the potential effects of BPA exposure to thyroid function during pregnancy.

Predicting ICU Interventions: A Transparent Decision Support Model Based on Multivariate Time Series Graph Convolutional Neural Network.

In this study, we present a novel approach for predicting interventions for patients in the intensive care unit using a multivariate time series graph convolutional neural network. Our method addresses two critical challenges: the need for timely and accurate decisions based on changing physiological signals, drug administration information, and static characteristics; and the need for interpretability in the decision-making process. Drawing on real-world ICU records from the MIMIC-III dataset, we demonstrate that our approach significantly improves upon existing machine learning and deep learning methods for predicting two targeted interventions, mechanical ventilation and vasopressors. Our model achieved an accuracy improvement from 81.6% to 91.9% and a F1 score improvement from 0.524 to 0.606 for predicting mechanical ventilation interventions. For predicting vasopressor interventions, our model achieved an accuracy improvement from 76.3% to 82.7% and a F1 score improvement from 0.509 to 0.619. We also assessed the interpretability by performing an adjacency matrix importance analysis, which revealed that our model uses clinically meaningful and appropriate features for prediction. This critical aspect can help clinicians gain insights into the underlying mechanisms of interventions, allowing them to make more informed and precise clinical decisions. Overall, our study represents a significant step forward in the development of decision support systems for ICU patient care, providing a powerful tool for improving clinical outcomes and enhancing patient safety.

Responses of Soil C, N, P and Enzyme Activities to Biological Soil Crusts in China: A Meta-Analysis.

Biological soil crusts (BSCs) are often referred to as the "living skin" of arid regions worldwide. Yet, the combined impact of BSCs on soil carbon (C), nitrogen (N), phosphorus (P), and enzyme activities remains not fully understood. This study identified, screened and reviewed 71 out of 2856 literature sources to assess the responses of soil C, N, P and enzyme activity to BSCs through a meta-analysis. The results indicated that BSC presence significantly increased soil C, N, P and soil enzyme activity, and this increasing effect was significantly influenced by the types of BSCs. Results from the overall effect showed that soil organic carbon (SOC), total nitrogen (TN), available nitrogen (AN), total phosphorus (TP), and available phosphorus (AP) increased by 107.88%, 84.52%, 45.43%, 27.46%, and 54.71%, respectively, and four soil enzyme activities (Alkaline Phosphatase, Cellulase, Sucrase, and Urease) increased by 93.65-229.27%. The highest increases in SOC, TN and AN content occurred in the soil covered with lichen crusts and moss crusts, and significant increases in Alkaline Phosphatase and Cellulase were observed in the soil covered with moss crusts and mixed crusts, suggesting that moss crusts can synergistically enhance soil C and N pool and enzyme activity. Additionally, variations in soil C, N, P content, and enzyme activity were observed under different environmental settings, with more pronounced improvements seen in coarse and medium-textured soils compared to fine-textured soils, particularly at a depth of 5 cm from the soil surface. BSCs in desert ecosystems showed more significant increases in SOC, TN, AN, and Alkaline Phosphatase compared to forest and grassland ecosystems. Specifically, BSCs at low altitude (≤500 m) with an annual average rainfall of 0-400 mm and an annual average temperature ≤ 10 °C were the most conducive to improving soil C, N, and P levels. Our results highlight the role of BSCs and their type in increasing soil C, N, P and enzyme activities, with these effects significantly impacted by soil texture, ecosystem type, and climatic conditions. The implications of these findings are crucial for soil enhancement, ecosystem revitalization, windbreak, and sand stabilization efforts in the drylands of China.

Comparative single-cell analyses identify shared and divergent features of human and mouse kidney development.

The mammalian kidney maintains fluid homeostasis through diverse epithelial cell types generated from nephron and ureteric progenitor cells. To extend a developmental understanding of the kidney's epithelial networks, we compared chromatin organization (single-nuclear assay for transposase-accessible chromatin sequencing [ATAC-seq]; 112,864 nuclei) and gene expression (single-cell/nuclear RNA sequencing [RNA-seq]; 109,477 cells/nuclei) in the developing human (10.6-17.6 weeks; n = 10) and mouse (post-natal day [P]0; n = 10) kidney, supplementing analysis with published mouse datasets from earlier stages. Single-cell/nuclear datasets were analyzed at a species level, and then nephron and ureteric cellular lineages were extracted and integrated into a common, cross-species, multimodal dataset. Comparative computational analyses identified conserved and divergent features of chromatin organization and linked gene activity, identifying species-specific and cell-type-specific regulatory programs. In situ validation of human-enriched gene activity points to human-specific signaling interactions in kidney development. Further, human-specific enhancer regions were linked to kidney diseases through genome-wide association studies (GWASs), highlighting the potential for clinical insight from developmental modeling.

Long-term expandable mouse and human-induced nephron progenitor cells enable kidney organoid maturation and modeling of plasticity and disease.

Nephron progenitor cells (NPCs) self-renew and differentiate into nephrons, the functional units of the kidney. Here, manipulation of p38 and YAP activity allowed for long-term clonal expansion of primary mouse and human NPCs and induced NPCs (iNPCs) from human pluripotent stem cells (hPSCs). Molecular analyses demonstrated that cultured iNPCs closely resemble primary human NPCs. iNPCs generated nephron organoids with minimal off-target cell types and enhanced maturation of podocytes relative to published human kidney organoid protocols. Surprisingly, the NPC culture medium uncovered plasticity in human podocyte programs, enabling podocyte reprogramming to an NPC-like state. Scalability and ease of genome editing facilitated genome-wide CRISPR screening in NPC culture, uncovering genes associated with kidney development and disease. Further, NPC-directed modeling of autosomal-dominant polycystic kidney disease (ADPKD) identified a small-molecule inhibitor of cystogenesis. These findings highlight a broad application for the reported iNPC platform in the study of kidney development, disease, plasticity, and regeneration.