High Aggressiveness Research Articles

Prognostic prediction models for postoperative patients with stage I to III colorectal cancer based on machine learning

BACKGROUND Colorectal cancer (CRC) is characterized by high heterogeneity, aggressiveness, and high morbidity and mortality rates. With machine learning (ML) algorithms, patient, tumor, and treatment features can be used to develop and validate models for predicting survival. In addition, important variables can be screened and different applications can be provided that could serve as vital references when making clinical decisions and potentially improving patient outcomes in clinical settings. AIM To construct prognostic prediction models and screen important variables for patients with stage I to III CRC. METHODS More than 1000 postoperative CRC patients were grouped according to survival time (with cutoff values of 3 years and 5 years) and assigned to training and testing cohorts (7:3). For each 3-category survival time, predictions were made by 4 ML algorithms (all-variable and important variable-only datasets), each of which was validated via 5-fold cross-validation and bootstrap validation. Important variables were screened with multivariable regression methods. Model performance was evaluated and compared before and after variable screening with the area under the curve (AUC). SHapley Additive exPlanations (SHAP) further demonstrated the impact of important variables on model decision-making. Nomograms were constructed for practical model application. RESULTS Our ML models performed well; the model performance before and after important parameter identification was consistent, and variable screening was effective. The highest pre- and postscreening model AUCs 95% confidence intervals in the testing set were 0.87 (0.81-0.92) and 0.89 (0.84-0.93) for overall survival, 0.75 (0.69-0.82) and 0.73 (0.64-0.81) for disease-free survival, 0.95 (0.88-1.00) and 0.88 (0.75-0.97) for recurrence-free survival, and 0.76 (0.47-0.95) and 0.80 (0.53-0.94) for distant metastasis-free survival. Repeated cross-validation and bootstrap validation were performed in both the training and testing datasets. The SHAP values of the important variables were consistent with the clinicopathological characteristics of patients with tumors. The nomograms were created. CONCLUSION We constructed a comprehensive, high-accuracy, important variable-based ML architecture for predicting the 3-category survival times. This architecture could serve as a vital reference for managing CRC patients.

Zingerone Facilitates Apoptosis in Triple Negative Breast Cancer Cells by Inducing Autophagy

ABSTRACTTriple negative breast cancer (TNBC) is characterized by high heterogenicity and aggressiveness and autophagy plays a complicated role in cancer development. Zingerone is reported to possess multiple pharmacological activities, including antitumors. This study explored the biological role and the relevant mechanisms of zingerone in TNBC. Following zingerone treatment, the viability of normal breast cancer cells MCF‐10A and TNBC cells (MDA‐MB‐231 and MDA‐MB‐468) was detected with CCK‐8 assay. The proliferation, migration and invasion of TNBC cells were detected with colony formation, wound healing, and transwell assays. Western blot was used to detect the expressions of migration‐, apoptosis‐ and autophagy‐related proteins. Flow cytometry was used to detect the cell apoptotic level and immunofluorescence assay measured the autophagy. The experimental data revealed that zingerone with varying concentrations suppressed cell viability, proliferation, migration and invasion while promoting the apoptosis in TNBC, which might be mediated by autophagy activation. Besides, zingerone decreased HDAC1 expression in TNBC cells and regulated autophagy via HDAC1. Collectively, zingerone impeded the malignant progression of TNBC via inducing HDAC1‐mediated autophagy.

Optimizing trade-offs between light transmittance and intraspecific competition under varying crop layouts in a maize–soybean strip relay cropping system

Light is one of the most important environmental factors for plant growth and development. In relay cropping systems, crop layouts influence light distribution, affecting light use efficiency (LUE). However, the response of light interception, light conversion, and LUE for relay maize and relay soybean to different crop layouts remains unclear. We aimed to quantify the effect of crop layout on intraspecific and interspecific competition, light interception, light conversion, LUE, and land productivity between relay maize and relay soybean. We conducted a field experiment for four consecutive years from 2017 to 2020 in Sichuan province, China, comparing different crop layouts (bandwidth 2.0 m, row ratio 2:2; bandwidth 2.4 m, row ratio 2:3; bandwidth 2.8 m, row ratio 2:4), with sole maize and sole soybean as controls. The results showed that relay maize in the 2.0 m bandwidth layout had the largest leaf area index and plant biomass, the lowest intraspecific competitive intensity and the highest aggressiveness. Compared to a bandwidth of 2.0 m, a bandwidth of 2.8 m significantly decreased relay maize leaf area index by 11% and plant biomass by 24%, while a 2.4 m bandwidth caused roughly half these reductions. The 2.0 m bandwidth layout also significantly improved crop light interception and LUE compared to sole maize. The light interception, light interception rate, light conversion rate and LUE in relay maize all decreased significantly with increasing bandwidth, but they increased in relay soybean. The increased light transmittance to the lower and middle canopy with increasing bandwidth did not compensate for the loss of relay maize yield caused by increased intraspecific competition. However, it enhanced the yield of relay soybeans. Increasing the bandwidth by 80 cm increased the relay maize intraspecific competition by 580%, and reduced maize yield by 33%, light interception by 12%, and LUE by 18%. In contrast, the relay soybean intraspecific competition was reduced by 64%, and the soybean yield was increased by 26%, light interception by 32% and LUE by 46%. Relay cropping systems with a 2.0 m bandwidth optimize the trade-off between light transmittance and intraspecific competition of relay crops. These systems achieve the highest LUE, group yield and economic benefits, making them a recommended crop layout for the southwest regions of China. Our study offers valuable insights for developing strip relay cropping systems that maximize light utilization and contributes to the theoretical understanding of efficient sunlight use in relay cropping practices.

Greater risk-taking by non-native than native shrimp: an advantage in a human-disturbed environment?

BackgroundThe invasion of non-native species into ecosystems is a growing human-induced problem. To control their spread and population growth, knowledge is needed on the factors that facilitate or impede their invasions. In animals, traits often associated with invasion success are high activity, boldness, and aggression. However, these traits also make individuals susceptible to predation, which could curb population growth. We investigated if a recent invader into the Baltic Sea, the shrimp Palaemon elegans, differs in risk-taking from a native shrimp, P. adspersus. We recorded activity, habitat choice, and response to perceived predation threat of both species.ResultsWe found the invading shrimp to take greater risks than the native one; while the native shrimp adjusted its behaviour to habitat structure and exposure to a perceived predator, the non-native shrimp did not, and it resumed normal activity sooner after a perceived predation threat. Despite the greater risk taking by the non-native shrimp, its population has grown rapidly during the last two decades in the investigated area and is now larger than that of the native shrimp.ConclusionsWe discuss plausible explanations for the population growth of the invader, including the recent decline in predatory fishes that could have reduced the cost of risk-taking, and anthropogenic eutrophication that has increased food abundance could have allowed the population growth. These results stress the need to assess the optimality of the behaviours of both native and non-native species when investigating the factors that influence invasion success in human-disturbed environments.

Abstract B010: Improving pancreatic cancer image classification with transfer learning: CD45 vs. PANCK

Abstract Pancreatic ductal adenocarcinoma (PDAC) is known for its high aggressiveness and is the fourth most common cause of death of cancer-related death in the United States. It is highly malignant and often goes undiagnosed until advanced stages due to its late-onset symptoms, resulting in poor prognosis. Using quantitative analyses of histological features, such as the expression of prognostic biomarker, can provide valuable insight to guide treatment decisions, monitor disease progression and predict outcomes. Previous researchers have found that CD45 and PANCK play a huge role in characterizing the tumor microenvironment of PDAC. One study using single-cell RNA sequencing compared the microenvironments of healthy pancreata and pancreatic tumors, revealing differences in cellular composition. Tumor samples showed a higher proportion of immune cells, including CD45+ cells, compared to heathy samples and utilized PANCK to differentiate between epithelial and non-epithelial cells. This study aims to enhance the accuracy of classifying pancreatic cancer pathological images based on prognostic markers using transfer learning techniques. We curated and pre-processed a dataset of pancreatic cancer pathological images with different prognostic markers. Using the pre-trained convolutional neural network (CNN) model VGG16, we fine-tuned it with our dataset to better differentiate between two prognostic markers, CD45 and PANCK. The model's performance was evaluated using a similarity matrix to illustrate distinctions among the two prognostic markers. Our results demonstrate that the transfer learning approach significantly improves classification accuracy, achieving confusion matrix validation results of 90% between CD45 and PANCK prognostic markers. SSIM values were relatively low, highlighting the ability of our model to differentiate between the two prognostic markers. The low SSIM value also shows variability within the two prognostic markers, indicating heterogeneity in structural changes due to pancreatic cancer. These findings indicate that transfer learning can be a powerful tool for improving the classification of pathological images and that there is notable variability in the structural features associated with different prognostic markers in pancreatic cancer. Citation Format: Miracle Thomas. Improving pancreatic cancer image classification with transfer learning: CD45 vs. PANCK [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B010.

Rational Design of a Tandem Activatable Fluorescent Probe for Differential Diagnosis and Therapeutic Assessment of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a formidable disease, distinguished by its high aggressiveness and dismal outcomes. Although leucine aminopeptidase (LAP) has been widely employed as a biomarker in biological imaging of HCC, it is still susceptible to interference from false-positive signals activated in injured liver tissues. In this study, based on the significant difference of GSH levels in alcohol-damaged liver tissues and tumor tissues, a dual-tandem activatable probe (PCLT) was designed for differential diagnosis and treatment guidance of HCC by near-infrared fluorescence (NIRF) imaging. This probe comprised a dual-locked hemicyanine dye decorated with a tetraethylene glycol chain and dual-recognition unit of glutathione (GSH) and LAP, which could be sequentially cleaved by GSH and LAP to restore its NIRF signal. PCLT excellently discriminated orthotopic HCC from ALI far earlier (7 days) than histological analysis (28 days) and exhibited higher specificity toward early orthotopic HCC than the single-locked probe (PCL). In addition, PCLT is capable of accurately delineating the tumor contour, assisting in surgical resection of HCC tumors under fluorescence visualization, and noninvasively assessing the antitumor effect of HCC chemotherapy during ferroptosis, thereby presenting promising clinical implications for clinical diagnosis and therapy of HCC.

Morphometric parameters of blood lymphocytes in American mink (Neogale vison) selected for tameness and defensive aggression toward humans

Although there is some evidence to suggest that there is a link between behavior and immune parameters in animals, this issue is still not well understood. In particular, there is a lack of understanding of how specific behaviors affect the size of immune cells. To address this issue, we investigated the relationship between behavior and the morphometric parameters of lymphocytes in American mink (Neogale vison) that have been selectively bred for aggression and tameness toward humans at the Institute of Cytology and Genetics in Novosibirsk, Russia, for 37 years. Minks with high ("-3") and medium ("-2") aggressiveness, moderate ("+ 3") and high tameness ("+ 6"), as well as those not affected by special behavior selection, were compared with each other. We found that aggressive and tame mink significantly differed in lymphocyte size, cytoplasm content and nucleus to cell ratio (NCR). The lymphocytes of tame mink were characterized by larger size, increased cytoplasm content and lower NCR compared to those of aggressive mink and unselected mink. Among the studied parameters, the largest differences were found in the size of lymphocytes between "+ 3" and unselected minks (p = 0.000018) and in the cytoplasm content between "+ 6" and unselected minks (p = 0.000039). Minks with similar behavior ("-3" and "-2", "+ 3" and "+ 6") showed no significant differences. Our data, combined with the strong correlation reported by other researchers between morphological characteristics of lymphocytes and cytokine levels indicates that selection for specific behaviors may lead to a rebalancing in the immune system.

Lenvatinib inhibits cholangiocarcinoma progression by targeting the FGF19/PI3K/AKT signaling pathway.

Cholangiocarcinoma (CCA) is known for its high aggressiveness and dismal prognosis, whose effectiveness of systemic therapy remains limited. As a multi-target drug, lenvatinib has exhibited promising effects in many solid tumors. However, the therapeutic role of lenvatinib in CCA is rarely investigated. Here, the in vitro assays including EdU, colony formation, transwell, wound healing, and apoptosis analyses demonstrated that lenvatinib significantly inhibited the proliferation, migration, and invasion, while simultaneously inducing apoptosis of CCA cells. Mechanistically, lenvatinib downregulated the expression of FGF19 and inactivated the PI3K/AKT signaling pathway. Depletion of FGF19 enhanced the anti-tumor effects of lenvatinib, which was attributed to the inhibition of p-PI3K and p-AKT expression in CCA cells. In contrast, overexpression of FGF19 activated the PI3K/AKT signaling pathway, thereby impairing the inhibitory effects of lenvatinib against CCA. In addition, the AKT inhibitor, MK-2206, reinforced the lenvatinib-induced CCA inhibition. Notably, the in vivo experiment confirmed that the subcutaneous tumorigenicity of CCA cells in nude mice was weakened by lenvatinib. Lenvatinib markedly downregulated the expression of FGF19, p-AKT, Ki-67, vimentin, and VEGF in the xenograft tumor tissues. Collectively, these findings demonstrated that lenvatinib inhibits CCA progression by targeting the FGF19/PI3K/AKT signaling pathway. The present study provides novel experimental evidence for the potential clinical application of lenvatinib in CCA, which also highlights the promising role of targeting FGF19 in combined therapeutic approaches for CCA.

Bioorthogonal Chemistry-Guided Inhalable Nanoprodrug to Circumvent Cisplatin Resistance in Orthotopic Nonsmall Cell Lung Cancer.

Pulmonary delivery of anticancer therapeutics has shown encouraging performance in treating nonsmall cell lung cancer (NSCLC), which is characterized by high aggressiveness and poor prognosis. Cisplatin, a key member of the family of DNA alkylating agents, is extensively employed during NSCLC therapy. However, the development of chemoresistance and the occurrence of side effects severely impede the long-term application of cisplatin-based chemotherapies. Herein, we propose a meaningful strategy to precisely treat cisplatin-resistant NSCLC based on the combination of bioorthogonal chemistry with an inhalation approach. Ethacraplatin (EA-Pt), a platinum prodrug (IV), was synthesized and encapsulated in nitric oxide (NO)-containing micelles to overcome cisplatin chemoresistance. By further modifying bioorthogonal molecules in this nanoplatform (EA-Pt@MDBCO), an improved targeting performance toward pulmonary cancerous regions is achieved after prelabeling with azide via inhalation. Upon entering acidic cancer cells, EA-Pt is swiftly released due to the pH sensitivity of bioorthogonal micelles, which enables its bifunctions to inhibit glutathione S-transferase activity and deplete intracellular glutathione, eventually reversing cisplatin resistance. Moreover, the released NO also improves the overall therapeutic outcome against NSCLC. Consequently, inhalable EA-Pt@MDBCO prelabeled by azide effectively inhibits the progression of cisplatin-resistant orthotopic NSCLC, offering a feasible nanostrategy to expand the treatment options for NSCLC.

The dynamics from reactive aggression to proactive aggression among adolescents: A multilevel chain mediating model

Reactive aggression and proactive aggression have long been growing public concerns and are two phenomena associated with each other. The magnitude of reactive aggression at baseline can predict the likelihood of subsequent proactive aggression. Yet, the potential motivation mechanisms of the relationship between reactive and proactive aggression remain little understood, especially through experimental research. To address this research limitation, the experimental design employed competitive reaction time tasks and reward-interference tasks to manipulate reactive aggression and positive outcome expectancy in a sample of 125 adolescents (Mage = 16.06; SD = 0.67; 50 % girls). Using repeated measures variance analysis, we found that compared to those in the low reactive aggression group, participants with high reactive aggression later showed higher proactive aggression aimed at the same monetary rewards. Furthermore, participants in the high positive outcome expectancy group also displayed higher proactive aggression, compared to those in the low and medium groups. Thereby, through multilevel mediation analysis, we confirmed robust relationships between reactive and proactive aggression mediated by positive outcome expectancy and moral disengagement. This study suggests that intervention programs should target the reduction of positive outcome expectancy and moral disengagement.

Advances in the Understanding of the Pathogenesis of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by high aggressiveness, high malignancy, and poor prognosis compared to other breast cancer subtypes. This review aims to explore recent advances in understanding TNBC and to provide new insights and potential references for clinical treatment. We examined current literature on TNBC to analyze molecular subtypes, genetic mutations, signaling pathways, mechanisms of drug resistance, and emerging therapies. Findings highlight key aspects of TNBC's molecular subtypes, relevant mutations, and pathways, alongside emerging treatments that target drug resistance mechanisms. These insights into TNBC pathogenesis may help guide future therapeutic strategies and improve clinical outcomes for patients with TNBC.

Critical role of non-coding RNA-mediated ferroptosis in urologic malignancies.

Urologic malignancies, characterized by their high aggressiveness and metastatic potential, pose a significant public health challenge globally. Ferroptosis, a novel mode of cell death, typically arises from intracellular iron ion overload and the accumulation of lipid peroxides. This process has been shown to play a crucial regulatory role in various pathological conditions, particularly in cancer, including urologic cancers. However, the comprehensive regulatory mechanisms underlying ferroptosis remain poorly understood, which somewhat limits its broader application in cancer therapy. Non-coding RNAs (ncRNAs), which encompass microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are non-coding transcripts that play pivotal roles in various physiological processes, such as proliferation, differentiation, apoptosis, and cell cycle regulation, by modulating the expression of target genes. The biological functions and potential regulatory mechanisms of ncRNAs in the context of cancer-related ferroptosis have been partially elucidated. Research indicates that ncRNAs can influence the progression of urologic cancers by affecting cell proliferation, migration, and drug resistance through the regulation of ferroptosis. Consequently, this review aims to clarify the functions and mechanisms of the ncRNA-ferroptosis axis in urologic cancers and to evaluate the clinical significance of ferroptosis-related ncRNAs, thereby providing new insights into cancer biology and therapeutic strategies that may ultimately benefit a diverse range of cancer patients.

Unfolding the aggression and locus of control paradigm in sportspersons and non-sportspersons

The present study investigated Aggression and Locus of Control on Combat Sports Persons, Non-Combat Sports Persons, and Non-Sports Persons. In this study, a sample of 240 individuals (80 Combat sports, 80 Non-Combat Sports & 80 Non-Sportspersons) was used through purposive sampling. The tools administered were the Buss and Perry Aggression Questionnaire by Arnold H. Buss and Mark Perry and Rotter’s Locus of Control Scale by Julian Rotter respectively. The objective of the study was to investigate Aggression and Locus of Control in males and females from Combat, Non-Combat, and Non-Sports persons. This research also aims to explore the relationship between Aggression and Locus of Control. Mean, t-test, F-value (ANOVA), and correlation have been computed over SPSS-16. Results suggest that males from Combat have higher Aggression than people from non-sports and non-combat sports. There is also a significant difference between non-sports persons and sports people over the Locus of Control, sports persons showed internal locus of control compared to non-sports persons who were higher on external locus of control. The result also indicates a significant relationship between the anger dimension of the Aggression and Locus of Control.

Effect of Natural Inhibitors on the Corrosion Properties of Grade 2 Titanium Alloy.

This study investigates the effects of natural inhibitors (pomegranate, algae, and tomato extracts) on the corrosion resistance of titanium (grade 2). To deepen understanding the inhibition mechanism, Molecular Dynamic (MD) and Monte Carlo (MC) simulations were employed to analyze adsorption behaviors and identify optimal adsorption sites on titanium oxide (TiO2) surfaces for compounds within the inhibitors. Results indicate non-flat adsorption orientations, with pomegranate peel extract components showing superior inhibition capabilities, attributed to the formation of strong O-H chemical bonds with the TiO2 surface. In the experimental part of the study Electrochemical Impedance Spectroscopy (EIS) and Potentiodynamic Polarization (PDP) were conducted. Two electrolytes were tested: a solution 3.5% NaCl and a solution 0.5 M NaOH. All the tests were performed with 5% of inhibitor and with the reference solution. Also, inhibition efficiency was calculated on the base of PDP tests. The study found that pomegranate extract can act as a good corrosion inhibitor for titanium alloy in aqueous solutions 0.5 M NaOH. This was demonstrated by the increase in the corrosion potential and impedance modulus and decrease in the corrosion current density after the addition of pomegranate extract to the solution. However, in a 3.5% NaCl solution, the efficacy of pomegranate extract was less pronounced, probably due to the high aggressivity of the electrolyte. Tomato and algae extract have instead shown very low inhibition effects in all the tested conditions.

Ki-67 as a Marker to Differentiate Burkitt Lymphoma and Diffuse Large B-cell Lymphoma: A Literature Review.

Burkitt lymphoma (BL) is a form of non-Hodgkin's lymphoma (NHL) that is characterized by high aggressiveness and arises from the germinal center of B cells. The prevalence of BLin adulthood is less than 5%. However, it encompasses 40% of all childhood NHL. Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma. It accounts for approximately 25% of all NHL cases worldwide. The differentiation between BL and DLBCL is more clear in theory than in daily practice. However, it is important because it implies different treatments. Compared to the other indolent small cell lymphomas, DLBCLs and BLs show higher Ki-67 index values. The Ki-67 levels in DLBCL typically range from 40% to 90%, while BL has a high Ki-67 positivity, nearing 100%. The aim of this article is to explore and review the function of Ki-67 as a differential marker for BL and DLBCL. An all-language literature search was conducted on MEDLINE, Cochrane, Embase, and Google Scholar until March 2024. The following search strings and Medical Subject Heading (MeSH) terms were used: "Ki-67," "Burkitt lymphoma," and "diffuse large B-cell lymphoma." We comprehensively reviewed the literature on BL, DLBCL, and the Ki-67 marker.

AKAP12 positive fibroblast determines immunosuppressive contexture and immunotherapy response in patients with TNBC by promoting macrophage M2 polarization

BackgroundTriple-negative breast cancer (TNBC) is a molecular subtype of breast cancer with high aggressiveness and poor prognosis. Cancer-associated fibroblasts (CAFs) are major components of the TNBC microenvironment and play an...

Detection of novel pathogenic variants of Fusarium oxysporum f. sp. lactucae in California

AbstractFusarium wilt, caused by the soilborne fungal pathogen Fusarium oxysporum f. sp. lactucae (FOL), is an economically important disease of lettuce (Lactuca sativa) throughout the world. Four pathogenic races of FOL are reported, though only race 1 is known to exist in the United States. Recently, Californian lettuce growers have expressed increasing concern about Fusarium wilt, as some race 1‐resistant cultivars have exhibited susceptibility, and some susceptible cultivars have displayed reduced disease severity. To determine whether such changes in disease patterns are responses to potentially novel variants, we collected infected plants from commercial fields in the Salinas Valley and Santa Maria regions, isolated the fungus, and conducted a series of pathogenicity tests using a set of FOL race differential cultivars over 2 years (2022 and 2023) in controlled conditions. Pathogenicity tests revealed two new FOL variants that elicited novel disease reaction patterns on the set of differential cultivars that have not been previously described. Isolates Fol621 and Fol621s were less aggressive on race 1‐susceptible Banchu Red Fire, designated Variant‐1. Isolate VSP‐0916 incited severe Fusarium wilt on race 1‐resistant Costa Rica No. 4, designated Variant‐2. Moreover, VSP‐0916 exhibited high aggressiveness and the ability to induce disease in other race 1‐resistant cultivars. This study is the first documentation, to our knowledge, of the occurrence of FOL‐inciting Fusarium wilt on race 1‐resistant lettuce in the United States. Our work provides valuable information critical for the development of Fusarium wilt management strategies, including broad‐spectrum resistance breeding efforts against multiple FOL races.

Comprehensive analysis of lactylation-related gene sets and mitochondrial functions in gastric adenocarcinoma: implications for prognosis and therapeutic strategies.

Gastric adenocarcinoma (STAD) is characterized by high heterogeneity and aggressiveness, leading to poor prognostic outcomes worldwide. This study explored the prognostic significance of lactylation-related gene sets and mitochondrial functions in STAD by integrating large-scale genomic datasets, including TCGA and several GEO datasets. We utilized Spatial transcriptomics and single-cell RNA sequencing to delineate the tumor microenvironment and assess the heterogeneity of cellular responses within the tumor. Additionally, the study identified distinct molecular subtypes within STAD that correspond with unique survival outcomes and immune profiles, enhancing the molecular classification beyond current paradigms. Prognostic models incorporating these molecular markers demonstrated superior predictive capabilities over existing models across multiple validation datasets. Furthermore, our analysis of immune landscapes revealed that variations in lactylation could influence immune cell infiltration and responsiveness, pointing towards novel avenues for tailored immunotherapy approaches. These comprehensive insights provide a foundation for targeted therapeutic strategies and underscore the potential of metabolic and immune modulation in improving STAD treatment outcomes.

Harnessing Gene Editing Technology for Tumor Microenvironment Modulation: An Emerging Anticancer Strategy.

Cancer is a multifaceted disease influenced by both intrinsic cellular traits and extrinsic factors, with the tumor microenvironment (TME) being crucial for cancer progression. To satisfy their high proliferation and aggressiveness, cancer cells always plunder large amounts of nutrients and release various signals to their surroundings, forming a dynamic TME with special metabolic, immune, microbial and physical characteristics. Due to the neglect of interactions between tumor cells and the TME, traditional cancer therapies often struggle with challenges such as drug resistance, low efficacy, and recurrence. Importantly, the development of gene editing technologies, particularly the CRISPR-Cas system, offers promising new strategies for cancer treatment. Combined with nanomaterial strategies, CRISPR-Cas technology exhibits precision, affordability, and user-friendliness with reduced side effects, which holds great promise for profoundly altering the TME at the genetic level, potentially leading to lasting anticancer outcomes. This review will delve into how CRISPR-Cas can be leveraged to manipulate the TME, examining its potential as a transformative anticancer therapy.

Early Socio-Emotional Difficulty as a Childhood Barrier to the Expected Benefits of Active Play: Associated Risks for School Engagement in Adolescence.

Active play allows children to develop social and cognitive skills, which could lead to higher school engagement. Little is known about the role of child socioemotional difficulty in these associations. This study aims to examine the interaction between active play and socioemotional difficulty in childhood and their prospective association with academic engagement in adolescence. The participants were 4537 children (51.1% boys) who were longitudinally followed, between ages 6 and 14 years, from the National Longitudinal Study on Children and Youth (NLSCY), Canada. Active play (weekly organized sport and unstructured physical activity outside of school hours) and child behavior (hyperactivity, anxiety, and relational difficulties) were reported by mothers for their children at age 6 years. Academic engagement was self-reported at age 14 years. Unstructured physical activity predicted lower subsequent school engagement for boys (β = -0.057, p < 0.05). Boys with high anxiety symptoms and high relational aggression who participated in more unstructured physical activity in childhood were subsequently less engaged in school (respectively, β = -0.066, p < 0.05 and β = -0.062, p < 0.05). Girls who partook in more organized sports showed lower school engagement in adolescence when they had high anxiety symptoms (β = -0.067, p < 0.05). Although past studies have highlighted the contribution of active play to school engagement, certain socioemotional difficulties could impede the child's ability to reap its benefits.