Unveiling the magic of mega-city block environments: investigating the intriguing mechanisms shaping children's spontaneous play preferences.

Introduction: This study delves into the spatial preferences of children for play spaces within high-density urban block environments, specifically targeting the area of Baihua Second Road in Shenzhen, China. Methods: Recognizing the critical role of play in children's development, and the unique challenges posed by dense urban settings, this research employs multiclass logistic regression models and negative binomial regression models to construct a detailed mathematical analysis of neighborhood spatial elements and children's play space preferences. Data was meticulously gathered through both objective observations of 14 different types of spaces within the block, and subjective assessments via children's responses to a series of environment photos, capturing the essence of over 3,000 child participants' interactions and choices. Results: Key findings reveal a pronounced preference among children for soft facility features and visually appealing spatial experiences, suggesting a nuanced understanding of play space needs beyond traditional playground designs. Notably, the study identifies that while cartoon-style designs in play facilities might increase moderate attractiveness, ordinary designs hold broader appeal, indicating a preference for diversity in play space aesthetics. These insights offer profound implications for urban planners and designers, advocating for a child-centered approach in the creation of urban play environments that prioritize aesthetic diversity, and the integration of natural elements. Conclusion: Moreover, the study situates Baihua Second Road as a paradigmatic case, illustrating the methodology and analytical framework applied in addressing the complex interplay between children's play preferences and urban spatial configurations. By incorporating a comprehensive data-driven analysis, this research contributes significantly to the discourse on child-friendly urban design, offering valuable strategies for cultivating inclusive and engaging urban play spaces for children amidst the constraints of high-density city living.

Cancer epigenetics: from laboratory studies and clinical trials to precision medicine.

Epigenetic dysregulation is a common feature of a myriad of human diseases, particularly cancer. Defining the epigenetic defects associated with malignant tumors has become a focus of cancer research resulting in the gradual elucidation of cancer cell epigenetic regulation. In fact, most stages of tumor progression, including tumorigenesis, promotion, progression, and recurrence are accompanied by epigenetic alterations, some of which can be reversed by epigenetic drugs. The main objective of epigenetic therapy in the era of personalized precision medicine is to detect cancer biomarkers to improve risk assessment, diagnosis, and targeted treatment interventions. Rapid technological advancements streamlining the characterization of molecular epigenetic changes associated with cancers have propelled epigenetic drug research and development. This review summarizes the main mechanisms of epigenetic dysregulation and discusses past and present examples of epigenetic inhibitors in cancer diagnosis and treatment, with an emphasis on the development of epigenetic enzyme inhibitors or drugs. In the final part, the prospect of precise diagnosis and treatment is considered based on a better understanding of epigenetic abnormalities in cancer.

ΔNp63α facilitates proliferation and migration, and modulates the chromatin landscape in intrahepatic cholangiocarcinoma cells.

p63 plays a crucial role in epithelia-originating tumours; however, its role in intrahepatic cholangiocarcinoma (iCCA) has not been completely explored. Our study revealed the oncogenic properties of p63 in iCCA and identified the major expressed isoform as ΔNp63α. We collected iCCA clinical data from The Cancer Genome Atlas database and analyzed p63 expression in iCCA tissue samples. We further established genetically modified iCCA cell lines in which p63 was overexpressed or knocked down to study the protein function/function of p63 in iCCA. We found that cells overexpressing p63, but not p63 knockdown counterparts, displayed increased proliferation, migration, and invasion. Transcriptome analysis showed that p63 altered the iCCA transcriptome, particularly by affecting cell adhesion-related genes. Moreover, chromatin accessibility decreased at p63 target sites when p63 binding was lost and increased when p63 binding was gained. The majority of the p63 bound sites were located in the distal intergenic regions and showed strong enhancer marks; however, active histone modifications around the Transcription Start Site changed as p63 expression changed. We also detected an interaction between p63 and the chromatin structural protein YY1. Taken together, our results suggest an oncogenic role for p63 in iCCA.

OsWRKY97, an Abiotic Stress-Induced Gene of Rice, Plays a Key Role in Drought Tolerance.

Drought stress is one of the major causes of crop losses. The WRKY families play important roles in the regulation of many plant processes, including drought stress response. However, the function of individual WRKY genes in plants is still under investigation. Here, we identified a new member of the WRKY families, OsWRKY97, and analyzed its role in stress resistance by using a series of transgenic plant lines. OsWRKY97 positively regulates drought tolerance in rice. OsWRKY97 was expressed in all examined tissues and could be induced by various abiotic stresses and abscisic acid (ABA). OsWRKY97-GFP was localized to the nucleus. Various abiotic stress-related cis-acting elements were observed in the promoters of OsWRKY97. The results of OsWRKY97-overexpressing plant analyses revealed that OsWRKY97 plays a positive role in drought stress tolerance. In addition, physiological analyses revealed that OsWRKY97 improves drought stress tolerance by improving the osmotic adjustment ability, oxidative stress tolerance, and water retention capacity of the plant. Furthermore, OsWRKY97-overexpressing plants also showed higher sensitivity to exogenous ABA compared with that of wild-type rice (WT). Overexpression of OsWRKY97 also affected the transcript levels of ABA-responsive genes and the accumulation of ABA. These results indicate that OsWRKY97 plays a crucial role in the response to drought stress and may possess high potential value in improving drought tolerance in rice.

Facile Synthesis of Basic Copper Carbonate Nanosheets for Photoacoustic Imaging-Guided Tumor Apoptosis and Ferroptosis and the Extension Exploration of the Synthesis Method.

Elimination of tumor cells using carbonate nanomaterials with tumor microenvironment-responsive capacity has been explored as an effective strategy. However, their therapeutic outcomes are always compromised by the relatively low intratumoral accumulation and limited synthesis method. Herein, a novel kind of basic copper carbonate nanosheets was designed and prepared using a green synthesis method for photoacoustic imaging-guided tumor apoptosis and ferroptosis therapy. These nanosheets were synthesized with the assistance of dopamine and ammonium bicarbonate (NH4HCO3) and the loading of glucose oxidase (GOx). NH4HCO3 could not only provide an alkaline environment for the polymerization of dopamine but also supply carbonates for the growth of nanosheets. The formed nanosheets displayed good acid and near-infrared light responsiveness. After intercellular uptake, they could be degraded to release Cu2+ and GOx, generating hydroxyl radicals through a Cu+-mediated Fenton-like reaction, consuming glucose, up-regulating H2O2 levels, and down-regulating GSH levels. Tumor elimination could be achieved by hydroxyl radical-induced apoptosis and ferroptosis. More amusingly, this synthesis method can be extended to several kinds of mono-element and multi-element carbonate nanomaterials (e.g., Fe, Mn, and Co), showing great potential for further tumor theranostics.

Recent advances in optical aptasensors for biomarkers in early diagnosis and prognosis monitoring of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver cancers and is one of the main malignant tumor types globally. It is essential to develop rapid, ultrasensitive, and accurate strategies for the diagnosis and surveillance of HCC. In recent years, aptasensors have attracted particular attention owing to their high sensitivity, excellent selectivity, and low production costs. Optical analysis, as a potential analytical tool, offers the advantages of a wide range of targets, rapid response, and simple instrumentation. In this review, recent progress in several types of optical aptasensors for biomarkers in early diagnosis and prognosis monitoring of HCC is summarized. Furthermore, we evaluate the strengths and limitations of these sensors and discuss the challenges and future perspectives for their use in HCC diagnosis and surveillance.

Integrative analysis indicates the prognostic value of circadian rhythm disruption in liver cancer: Potential for therapeutic targeting.

Circadian rhythms regulate various biological processes, such as cell division and metabolism. Circadian rhythm disruption (CRD) is often associated with malignant tumor progression and poor prognosis. However, the effect of CRD on liver cancer prognosis has not been systematically analyzed or fully elucidated. Here, we developed a method to quantify and assess intratumoral CRD in a single-cell transcriptomic analysis of liver cancer and systematically analyzed the role of CRD in tumor progression and prognosis. Furthermore, a LASSO-Cox regression model based on 14 CRD genes was used to predict overall patient survival across multiple datasets. We found that malignant cells with high CRD scores were enriched in specific metabolic pathways, such as fatty acid metabolism and the trichloroacetic acid cycle. Intercellular communication analysis suggested that CRD regulates chemokine-mediated interactions. With the bulk transcriptomic datasets, we determined that LiverCRD scores were significantly correlated with macrophage infiltration levels and could guide targeted immunotherapy and chemotherapy strategies. In addition, LiverCRD is also associated with the mutational landscape-for example, TP53 mutation frequency was higher in high-CRD samples. Finally, the 14-gene-based LASSO-Cox regression model could accurately predict overall patient survival across datasets. In conclusion, Our proposed analysis reflects the relationship between CRD and the immune environment in liver cancer, suggesting that CRD may serve as a potential prognostic indicator. Our results may help guide targeted anti-tumor strategies.

Sorafenib-Loaded Copper Peroxide Nanoparticles with Redox Balance Disrupting Capacity for Enhanced Chemodynamic Therapy against Tumor Cells.

Chemodynamic therapy (CDT) is a promising hydroxyl radical (•OH)-mediated tumor therapeutic method with desirable tumor specificity and minimal side effects. However, the efficiency of CDT is restricted by the pH condition, insufficient H2O2 level, and overexpressed reductive glutathione (GSH), making it challenging to solve these problems simultaneously to improve the efficacy of CDT. Herein, a kind of polyvinylpyrrolidone-stabilized, sorafenib-loaded copper peroxide (CuO2-PVP-SRF) nanoparticle (NPs) was designed and developed for enhanced CDT against tumor cells through the synergetic pH-independent Fenton-like, H2O2 self-supplying, and GSH depletion strategy. The prepared CuO2-PVP-SRF NPs can be uptaken by 4T1 cells to specifically release Cu2+, H2O2, and SRF under acidic conditions. The intracellular GSH can be depleted by SRF-induced system xc- dysfunction and Cu2+-participated redox reaction, causing the inactivation of GPX4 and generating Cu+. A great amount of •OH was produced in this reducing capacity-disrupted condition by the Cu+-mediated Fenton-like reaction, causing cell apoptosis and lipid hydroperoxide accumulation-induced ferroptosis. They display an excellent 4T1 cell killing outcome through the improved •OH production capacity. The CuO2-PVP-SRF NPs display elevated therapeutic efficiency of CDT and show good promise in further tumor treatment applications.

Regulation of 3D Organization and Its Role in Cancer Biology.

Three-dimensional (3D) genomics is the frontier field in the post-genomics era, its foremost content is the relationship between chromatin spatial conformation and regulation of gene transcription. Cancer biology is a complex system resulting from genetic alterations in key tumor oncogenes and suppressor genes for cell proliferation, DNA replication, cell differentiation, and homeostatic functions. Although scientific research in recent decades has revealed how the genome sequence is mutated in many cancers, high-order chromosomal structures involved in the development and fate of cancer cells represent a crucial but rarely explored aspect of cancer genomics. Hence, dissection of the 3D genome conformation of cancer helps understand the unique epigenetic patterns and gene regulation processes that distinguish cancer biology from normal physiological states. In recent years, research in tumor 3D genomics has grown quickly. With the rapid progress of 3D genomics technology, we can now better determine the relationship between cancer pathogenesis and the chromatin structure of cancer cells. It is becoming increasingly explicit that changes in 3D chromatin structure play a vital role in controlling oncogene transcription. This review focuses on the relationships between tumor gene expression regulation, tumor 3D chromatin structure, and cancer phenotypic plasticity. Furthermore, based on the functional consequences of spatial disorganization in the cancer genome, we look forward to the clinical application prospects of 3D genomic biomarkers.

OsSCL30 overexpression reduces the tolerance of rice seedlings to low temperature, drought and salt.

Rice is one of the main food crops for the world population. Various abiotic stresses, such as low temperature, drought, and high salinity, affect rice during the entire growth period, determining its yield and quality, and even leading to plant death. In this study, by constructing overexpression vectors D-163 + 1300:OsSCL30 and D-163 + 1300-AcGFP:OsSCL30-GFP, the mechanism of action of OsSCL30 in various abiotic stresses was explored. Bioinformatics analysis showed that OsSCL30 was located on the chromosome 12 of rice Nipponbare, belonging to the plant-specific SCL subfamily of the SR protein family. The 1500 bp section upstream of the open reading frame start site contains stress-related cis-acting elements such as ABRE, MYC, and MYB. Under normal conditions, the expression of OsSCL30 was higher in leaves and leaf sheaths. The results of reverse transcription polymerase chain reaction showed that the expression of OsSCL30 decreased after low temperature, drought and salt treatment. In root cells OsSCL30 was localized in the nuclei. The results of the rice seedling tolerance and recovery tests showed that overexpression of OsSCL30 diminished the resistance to low temperature, drought and salt stresses in transgenic rice and resulted in larger accumulation of reactive oxygen species. This study is of great significance for exploring the response mechanisms of SR proteins under abiotic stresses.

ISSMF: Integrated semantic and spatial information of multi-level features for automatic segmentation in prenatal ultrasound images.

As an effective way of routine prenatal diagnosis, ultrasound (US) imaging has been widely used recently. Biometrics obtained from the fetal segmentation shed light on fetal health monitoring. However, the segmentation in US images has strict requirements for sonographers on accuracy, making this task quite time-consuming and tedious. In this paper, we use DeepLabv3+ as the backbone and propose an Integrated Semantic and Spatial Information of Multi-level Features (ISSMF) based network to achieve the automatic and accurate segmentation of four parts of the fetus in US images while most of the previous works only segment one or two parts. Our contributions are threefold. First, to incorporate semantic information of high-level features and spatial information of low-level features of US images, we introduce a multi-level feature fusion module to integrate the features at different scales. Second, we propose to leverage the content-aware reassembly of features (CARAFE) upsampler to deeply explore the semantic and spatial information of multi-level features. Third, in order to alleviate performance degradation caused by batch normalization (BN) when batch size is small, we use group normalization (GN) instead. Experiments on four parts of fetus in US images show that our method outperforms the U-Net, DeepLabv3+ and the U-Net++ and the biometric measurements based on our segmentation results are pretty close to those derived from sonographers with ten-year work experience.

Myc suppresses male-male courtship in Drosophila.

Despite strong natural selection on species, same-sex sexual attraction is widespread across animals, yet the underlying mechanisms remain elusive. Here, we report that the proto-oncogene Myc is required in dopaminergic neurons to inhibit Drosophila male-male courtship. Loss of Myc, either by mutation or neuro-specific knockdown, induced males' courtship propensity toward other males. Our genetic screen identified DOPA decarboxylase (Ddc) as a downstream target of Myc. While loss of Ddc abrogated Myc depletion-induced male-male courtship, Ddc overexpression sufficed to trigger such behavior. Furthermore, Myc-depleted males exhibited elevated dopamine level in a Ddc-dependent manner, and their male-male courtship was blocked by depleting the dopamine receptor DopR1. Moreover, Myc directly inhibits Ddc transcription by binding to a target site in the Ddc promoter, and deletion of this site by genome editing was sufficient to trigger male-male courtship. Finally, drug-mediated Myc depletion in adult neurons by GeneSwitch technique sufficed to elicit male-male courtship. Thus, this study uncovered a novel function of Myc in preventing Drosophila male-male courtship, and supports the crucial roles of genetic factors in inter-male sexual behavior.

Rox8 promotes microRNA-dependent yki messenger RNA decay.

The Hippo pathway is an evolutionarily conserved regulator of organ growth and tumorigenesis. In Drosophila, oncogenic RasV12 cooperates with loss-of-cell polarity to promote Hippo pathway-dependent tumor growth. To identify additional factors that modulate this signaling, we performed a genetic screen utilizing the Drosophila RasV12/lgl-/- in vivo tumor model and identified Rox8, a RNA-binding protein (RBP), as a positive regulator of the Hippo pathway. We found that Rox8 overexpression suppresses whereas Rox8 depletion potentiates Hippo-dependent tissue overgrowth, accompanied by altered Yki protein level and target gene expression. Mechanistically, Rox8 directly binds to a target site located in the yki 3' UTR, recruits and stabilizes the targeting of miR-8-loaded RISC, which accelerates the decay of yki messenger RNA (mRNA). Moreover, TIAR, the human ortholog of Rox8, is able to promote the degradation of yki mRNA when introduced into Drosophila and destabilizes YAP mRNA in human cells. Thus, our study provides in vivo evidence that the Hippo pathway is posttranscriptionally regulated by the collaborative action of RBP and microRNA (miRNA), which may provide an approach for modulating Hippo pathway-mediated tumorigenesis.

Lic regulates JNK-mediated cell death in Drosophila.

OBJECTIVES: The evolutionary conserved JNK pathway plays crucial role in cell death, yet factors that modulate this signalling have not been fully disclosed. In this study, we aim to identify additional factors that regulate JNK signalling in cell death, and characterize the underlying mechanisms. MATERIALS AND METHODS: Drosophila were raised on standard media, and cross was carried out at 25°C. The Gal4/UAS system was used to express proteins or RNAi in a specific temporal and spatial pattern. Gene expression was revealed by GFP fluorescence, X-gal staining or immunostaining of 3rd instar larval eye and wing discs. Cell death was visualized by acridine orange (AO) staining. Images of fly eyes and wings were taken by OLYMPUS microscopes. RESULTS: We found that licorne (lic) encoding the Drosophila MKK3 is an essential regulator of JNK-mediated cell death. Firstly, loss of lic suppressed ectopic Egr-triggered JNK activation and cell death in eye and wing development. Secondary, lic is necessary for loss-of-cell polarity-induced, physiological JNK-dependent cell death in wing development. Thirdly, Lic overexpression is sufficient to initiate JNK-mediated cell death in developing eyes and wings. Furthermore, ectopic Lic activates JNK signalling by promoting JNK phosphorylation. Finally, genetic epistatic analysis confirmed that Lic acts in parallel with Hep in the Egr-JNK pathway. CONCLUSIONS: This study not only identified Lic as a novel component of the JNK signalling, but also disclosed the crucial roles and mechanism of Lic in cell death.

MKK3 modulates JNK-dependent cell migration and invasion.

The c-Jun N-terminal kinase (JNK) pathway plays essential roles in regulating a variety of physiological processes including cell migration and invasion. To identify critical factors that regulate JNK-dependent cell migration, we carried out a genetic screen in Drosophila based on the loss-of-cell polarity-triggered cell migration in the wing epithelia, and identified MKK3 licorne (lic) as an essential regulator of JNK-mediated cell migration and invasion. We found that loss of lic suppressed ptc > scrib-IR or ptc > Egr triggered cell migration in the wing epithelia, and Rasv12/lgl-/- induced tumor invasion in the eye discs. In addition, ectopic expression of Lic is sufficient to induce JNK-mediated but p38-independent cell migration, and cooperate with oncogenic Ras to promote tumor invasion. Consistently, Lic is able to activate JNK signaling by phosphorylating JNK, which up-regulates the matrix metalloproteinase MMP1 and integrin, characteristics of epithelial-mesenchymal transition (EMT). Moreover, lic is required for physiological JNK-mediate cell migration in thorax development. Finally, expression of human MKK3 in Drosophila is able to initiate JNK-mediated cell migration, cooperates with oncogenic Ras to trigger tumor invasion, and rescue loss-of-lic induced thorax closure defect. As previous studies suggest that MKK3 specifically phosphorylates and activates p38MAPK, our data provide the first in vivo evidence that MKK3 regulates JNK-dependent cell migration and invasion, a process evolutionarily conserved from flies to human.

Genetic diversity and characterization of arsenic-resistant endophytic bacteria isolated from Pteris vittata, an arsenic hyperaccumulator.

BACKGROUND: Alleviating arsenic (As) contamination is a high-priority environmental issue. Hyperaccumulator plants may harbor endophytic bacteria able to detoxify As. Therefore, we investigated the distribution, diversity, As (III) resistance levels, and resistance-related functional genes of arsenite-resistant bacterial endophytes in Pteris vittata L. growing in a lead-zinc mining area with different As contamination levels. RESULTS: A total of 116 arsenite-resistant bacteria were isolated from roots of P. vittata with different As concentrations. Based on the 16S rRNA gene sequence analysis of representative isolates, the isolates belonged to Proteobacteria, Actinobacteria, and Firmicutes. Major genera found were Agrobacterium, Stenotrophomonas, Pseudomonas, Rhodococcus, and Bacillus. The most highly arsenite-resistant bacteria (minimum inhibitory concentration > 45 mM) were isolated from P. vittata with high As concentrations and belonged to the genera Agrobacterium and Bacillus. The strains with high As tolerance also showed high levels of indole-3-acetic acid (IAA) production and carried arsB/ACR3(2) genes. The arsB and ACR3(2) were most likely horizontally transferred among the strains. CONCLUSION: The results of this study suggest that P. vittata plants with high As concentrations may select diverse arsenite-resistant bacteria; this diversity might, at least partly, be a result of horizontal gene transfer. These diverse endophytic bacteria are potential candidates to enhance phytoremediation techniques.

Hippo signaling promotes JNK-dependent cell migration.

Overwhelming studies show that dysregulation of the Hippo pathway is positively correlated with cell proliferation, growth, and tumorigenesis. Paradoxically, the detailed molecular roles of the Hippo pathway in cell invasion remain debatable. Using a Drosophila invasion model in wing epithelium, we show herein that activated Hippo signaling promotes cell invasion and epithelial-mesenchymal transition through JNK, as inhibition of JNK signaling dramatically blocked Hippo pathway activation-induced matrix metalloproteinase 1 expression and cell invasion. Furthermore, we identify bantam-Rox8 modules as essential components downstream of Yorkie in mediating JNK-dependent cell invasion. Finally, we confirm that YAP (Yes-associated protein) expression negatively regulates TIA1 (Rox8 ortholog) expression and cell invasion in human cancer cells. Together, these findings provide molecular insights into Hippo pathway-mediated cell invasion and also raise a noteworthy concern in therapeutic interventions of Hippo-related cancers, as simply inhibiting Yorkie or YAP activity might paradoxically accelerate cell invasion and metastasis.