Statins improve cardiac endothelial function to prevent heart failure with preserved ejection fraction through upregulating circRNA-RBCK1.

Heart failure with preserved ejection fraction (HFpEF) is associated with endothelial dysfunction. We have previously reported that statins prevent endothelial dysfunction through inhibition of microRNA-133a (miR-133a). This study is to investigate the effects and the underlying mechanisms of statins on HFpEF. Here, we show that statins upregulate the expression of a circular RNA (circRNA-RBCK1) which is co-transcripted with the ring-B-box-coiled-coil protein interacting with protein kinase C-1 (RBCK1) gene. Simultaneously, statins increase activator protein 2 alpha (AP-2α) transcriptional activity and the interaction between circRNA-RBCK1 and miR-133a. Furthermore, AP-2α directly interacts with RBCK1 gene promoter in endothelial cells. In vivo, lovastatin improves diastolic function in male mice under HFpEF, which is abolished by loss function of endothelial AP-2α or circRNA-RBCK1. This study suggests that statins upregulate the AP-2α/circRNA-RBCK1 signaling to suppress miR-133a in cardiac endothelial cells and prevent diastolic dysfunction in HFpEF.

A radiomics signature derived from CT imaging to predict MSI status and immunotherapy outcomes in gastric cancer: a multi-cohort study.

BACKGROUND: Accurate microsatellite instability (MSI) testing is essential for identifying gastric cancer (GC) patients eligible for immunotherapy. We aimed to develop and validate a CT-based radiomics signature to predict MSI and immunotherapy outcomes in GC. METHODS: This retrospective multicohort study included a total of 457 GC patients from two independent medical centers in China and The Cancer Imaging Archive (TCIA) databases. The primary cohort (n = 201, center 1, 2017-2022), was used for signature development via Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression analysis. Two independent immunotherapy cohorts, one from center 1 (n = 184, 2018-2021) and another from center 2 (n = 43, 2020-2021), were utilized to assess the signature's association with immunotherapy response and survival. Diagnostic efficiency was evaluated using the area under the receiver operating characteristic curve (AUC), and survival outcomes were analyzed via the Kaplan-Meier method. The TCIA cohort (n = 29) was included to evaluate the immune infiltration landscape of the radiomics signature subgroups using both CT images and mRNA sequencing data. RESULTS: Nine radiomics features were identified for signature development, exhibiting excellent discriminative performance in both the training (AUC: 0.851, 95%CI: 0.782, 0.919) and validation cohorts (AUC: 0.816, 95%CI: 0.706, 0.926). The radscore, calculated using the signature, demonstrated strong predictive abilities for objective response in immunotherapy cohorts (AUC: 0.734, 95%CI: 0.662, 0.806; AUC: 0.724, 95%CI: 0.572, 0.877). Additionally, the radscore showed a significant association with PFS and OS, with GC patients with a low radscore experiencing a significant survival benefit from immunotherapy. Immune infiltration analysis revealed significantly higher levels of CD8 + T cells, activated CD4 + B cells, and TNFRSF18 expression in the low radscore group, while the high radscore group exhibited higher levels of T cells regulatory and HHLA2 expression. CONCLUSION: This study developed a robust radiomics signature with the potential to serve as a non-invasive biomarker for GC's MSI status and immunotherapy response, demonstrating notable links to post-immunotherapy PFS and OS. Additionally, distinct immune profiles were observed between low and high radscore groups, highlighting their potential clinical implications.

The safety, feasibility and oncological outcomes of laparoscopic completion total gastrectomy for remnant gastric cancer: a prospective study with 3-year follow-up (FUGES-004 study).

BACKGROUND: The efficacy of laparoscopic completion total gastrectomy (LCTG) for remnant gastric cancer (RGC) remains controversial. METHODS: The primary outcome was postoperative morbidity within 30 days after surgery. Secondary outcomes included 3-year disease-free survival (DFS), 3-year overall survival (OS), and recurrence. Inverse probability treatment weighted (IPTW) was used to balance the baseline between LCTG and OCTG. RESULTS: Final analysis included 46 patients with RGC who underwent LCTG at the FJMUUH between June 2016 and June 2020. The historical control group comprised of 160 patients who underwent open completion total gastrectomy (OCTG) in the six tertiary teaching hospitals from CRGC-01 study. After IPTW, no significant difference was observed between the LCTG and OCTG groups in terms of incidence (LCTG vs. OCTG: 28.0% vs. 35.0%, P=0.379) or severity of complications within 30 days after surgery. Compared with OCTG, LCTG resulted in better short-term outcomes and faster postoperative recovery. However, the textbook outcome rate was comparable between the two groups (45.9% vs. 32.8%, P=0.107). Additionally, the 3-year DFS and 3-year OS of LCTG were comparable to those of OCTG (DFS: log-rank P=0.173; OS: log-rank P=0.319). No significant differences in recurrence type, mean recurrence time, or 3-year cumulative hazard of recurrence were observed between the two groups (all P>0.05). Subgroup analyses and concurrent comparisons demonstrated similar trends. CONCLUSIONS: This prospective study suggested that LCTG was non-inferior to OCTG in both short- and long-term outcomes. In experienced centers, LCTG may be considered as a viable treatment option for RGC.

Impact of a Clinical Nursing Teaching Model Based on Institutional Cooperation on Teaching Quality of Nursing Programs in Colleges and Universities and Effectiveness of Internship for Undergraduate Nurses.

Objective: To observe the impact of a clinical nursing teaching model based on institutional collaboration on the teaching quality of nursing programs in colleges and universities and the effectiveness of undergraduate practical nurses in practice. Methods: One hundred and twenty-three undergraduate student nurses graduating from June 2020 to July 2021 were selected for the study, 59 of whom received the traditional teaching model (control group) and 64 of whom received the institutional cooperative teaching model (research group). Upon completion of their internship, a clinical nursing skills assessment was conducted for the two groups, and the clinical internship performance was evaluated using the self-assessment scale of clinical practice behavior performance of nursing undergraduates. A teaching evaluation questionnaire was used to survey the intern nurses' evaluation of the teaching model and their satisfaction with the teaching model was surveyed in the middle and after the completion of the internship, respectively. Upon completion of the internship, the intern nurses filled out a self-satisfaction evaluation form. Results: The research group had a lower failure rate than the control group and a higher excellent rate than the control group (P < .05). There were no differences in the scores of the professional and self-development domains between the two groups (P > .05), while for all other clinical placement performances, the scores were higher in the research group than in the control group (P < .05). In addition, the research group had higher subject presentation, post-lesson acquisition, total score, and teaching satisfaction than the control group (P < .05). In terms of self-satisfaction, the number of satisfied intern nurses was also higher than the control group (P < .05). Conclusion: The reform of clinical nursing teaching mode based on institutional cooperation can effectively improve the quality of nursing teaching in universities and the effectiveness of undergraduate practical nursing.

Resolving neuroinflammatory and social deficits in ASD model mice: Dexmedetomidine downregulates NF-κB/IL-6 pathway via α2AR.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that severely affects individuals' daily life and social development. Unfortunately, there are currently no effective treatments for ASD. Dexmedetomidine (DEX) is a selective agonist of α2 adrenergic receptor (α2AR) and is widely used as a first-line medication for sedation and hypnosis in clinical practice. In recent years, there have been reports suggesting its potential positive effects on improving emotional and cognitive functions. However, whether dexmedetomidine has therapeutic effects on the core symptoms of ASD, namely social deficits and repetitive behaviors, remains to be investigated. In the present study, we employed various behavioral tests to assess the phenotypes of animals, including the three-chamber, self-grooming, marble burying, open field, and elevated plus maze. Additionally, electrophysiological recordings, western blotting, qPCR were mainly used to investigate and validate the potential mechanisms underlying the role of dexmedetomidine. We found that intraperitoneal injection of dexmedetomidine in ASD model mice-BTBR T+ Itpr3tf/J (BTBR) mice could adaptively improve their social deficits. Further, we observed a significant reduction in c-Fos positive signals and interleukin-6 (IL-6) expression level in the prelimbic cortex (PrL) of the BTBR mice treated with dexmedetomidine. Enhancing or inhibiting the action of IL-6 directly affects the social behavior of BTBR mice. Mechanistically, we have found that NF-κB p65 is a key pathway regulating IL-6 expression in the PrL region. In addition, we have confirmed that the α2AR acts as a receptor switch mediating the beneficial effects of dexmedetomidine in improving social deficits. This study provides the first evidence of the beneficial effects of dexmedetomidine on core symptoms of ASD and offers a theoretical basis and potential therapeutic approach for the clinical treatment of ASD.

Temporospatial hierarchy and allele-specific expression of zygotic genome activation revealed by distant interspecific urochordate hybrids.

Zygotic genome activation (ZGA) is a universal process in early embryogenesis of metazoan, when the quiescent zygotic nucleus initiates global transcription. However, the mechanisms related to massive genome activation and allele-specific expression (ASE) remain not well understood. Here, we develop hybrids from two deeply diverged (120 Mya) ascidian species to symmetrically document the dynamics of ZGA. We identify two coordinated ZGA waves represent early developmental and housekeeping gene reactivation, respectively. Single-cell RNA sequencing reveals that the major expression wave exhibits spatial heterogeneity and significantly correlates with cell fate. Moreover, allele-specific expression occurs in a species- rather than parent-related manner, demonstrating the divergence of cis-regulatory elements between the two species. These findings provide insights into ZGA in chordates.

Dynamics of Chromatin Opening across Larval Development in the Urochordate Ascidian Ciona savignyi.

Ascidian larvae undergo tail elongation and notochord lumenogenesis, making them an ideal model for investigating tissue morphogenesis in embryogenesis. The cellular and mechanical mechanisms of these processes have been studied; however, the underlying molecular regulatory mechanism remains to be elucidated. In this study, assays for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA sequencing (RNA-seq) were applied to investigate potential regulators of the development of ascidian Ciona savignyi larvae. Our results revealed 351 and 138 differentially accessible region genes through comparisons of ATAC-seq data between stages 21 and 24 and between stages 24 and 25, respectively. A joint analysis of RNA-seq and ATAC-seq data revealed a correlation between chromatin accessibility and gene transcription. We further verified the tissue expression patterns of 12 different genes. Among them, Cs-matrix metalloproteinase 24 (MMP24) and Cs-krüppel-like factor 5 (KLF5) were highly expressed in notochord cells. Functional assay results demonstrated that both genes are necessary for notochord lumen formation and expansion. Finally, we performed motif enrichment analysis of the differentially accessible regions in different tailbud stages and summarized the potential roles of these motif-bearing transcription factors in larval development. Overall, our study found a correlation between gene expression and chromatin accessibility and provided a vital resource for understanding the mechanisms of the development of ascidian embryos.

Development and implementation of a high-fidelity simulation training course for medical and nursing collaboration based on the Fink integrated course design model.

Aim: The purpose of this study is to examine the design and implementation of a high-fidelity simulation training course for medical and nursing collaboration, based on the Fink integrated course design model. Additionally, the study aims to validate the teaching effectiveness of the course. Background: Previous empirical studies have highlighted the effectiveness of collaborative healthcare education in institutional teaching and hospital training. However, the development of healthcare collaborative education in China has been slow to develop in China. In recent years, Chinese nursing educators and researchers have shown interest in utilizing high-fidelity simulators for healthcare collaborative education. These simulators help address the limitations of traditional nursing teaching and healthcare separation simulation. Nevertheless, a standardized simulation interprofessional education curriculum is still lacking. Therefore, nursing educators need to develop a standardized high-fidelity simulation training curriculum for healthcare collaboration, guided by established science curriculum development theories. Methods: A high-fidelity simulation training course on healthcare collaboration was designed based on the Fink integrated curriculum design model. The course was taught to 14 nursing students and 8 clinical medicine students from March to July 2022. To comprehensively evaluate the effectiveness of the healthcare collaboration high-fidelity simulation training course, several assessment tools were used. These included course grades, satisfaction and self-confidence scales, simulation teaching practice scales, healthcare collaboration attitude scales, critical thinking skills scales, and semi-structured interviews. Results: After the course was implemented, students demonstrated high overall scores (79.19 ± 5.12) and reported high satisfaction ratings (4.44 ± 0.37). They also exhibited increased self-confidence (4.16 ± 0.33). Additionally, students evaluated all four dimensions of the course teaching practice scale positively. Furthermore, the study demonstrated significant improvements in various aspects, such as attitudes toward medical and nursing collaboration (t = -7.135, P < 0.01), shared education and teamwork (t = -3.247, P = 0.002), job autonomy for nurses (t = -1.782, P = 0.000), and reduced physician dominance (t = -6.768, P = 0.000). The critical thinking skills of the students showed significant improvement, with higher scores in truth-seeking (t = -3.052, P = 0.004), analytical ability (t = -2.561, P = 0.014), systematic ability (t = -3.491, P = 0.001), self-confidence in critical thinking (t = -4.024, P = 0.000), and curiosity (t = -5.318, P = 0.000) compared to their scores before the course (all P < 0.05). The interviews showed that the course's student-centered approach enabled active learning. Students suggested enhancing teaching cases and allocating more time for reflection and summarization. Conclusion: The study successfully designed a high-fidelity simulation training course for healthcare collaboration by utilizing the Fink integrated curriculum design model. The findings provide valuable insights for the development of standardized curricula and healthcare collaboration education in China. Moreover, the course adheres to best practice principles, fostering improved attitudes toward healthcare collaboration and enhancing students' healthcare collaboration and clinical thinking skills.

Structure Responsible for the Superconducting State in La3Ni2O7 at High-Pressure and Low-Temperature Conditions.

Very recently, a new superconductor with Tc = 80 K has been reported in nickelate (La3Ni2O7) at around 15-40 GPa conditions (Nature, 621, 493, 2023), which is the second type of unconventional superconductor, besides cuprates, with Tc above liquid nitrogen temperature. However, the phase diagram plotted in this report was mostly based on the transport measurement under low-temperature and high-pressure conditions, and the assumed corresponding X-ray diffraction (XRD) results were carried out at room temperature. This encouraged us to carry out in situ high-pressure and low-temperature synchrotron XRD experiments to determine which phase is responsible for the high Tc state. In addition to the phase transition from the orthorhombic Amam structure to the orthorhombic Fmmm structure, a tetragonal phase with the space group of I4/mmm was discovered when the sample was compressed to around 19 GPa at 40 K where the superconductivity takes place in La3Ni2O7. The calculations based on this tetragonal structure reveal that the electronic states that approached the Fermi energy were mainly dominated by the eg orbitals (3dz2 and 3dx2-y2) of Ni atoms, which are located in the oxygen octahedral crystal field. The correlation between Tc and this structural evolution, especially Ni-O octahedra regularity and the in-plane Ni-O-Ni bonding angles, is analyzed. This work sheds new light to identify what is the most likely phase responsible for superconductivity in double-layered nickelate.

Comparative transcriptome and metabolome profiles of the leaf and fruits of a Xianjinfeng litchi budding mutant and its mother plant.

Background: Litchi (Litchi chinensis) is an important sub-tropical fruit in the horticulture market in China. Breeding for improved fruit characteristics is needed for satisfying consumer demands. Budding is a sustainable method for its propagation. During our ongoing breeding program, we observed a litchi mutant with flat leaves and sharp fruit peel cracking in comparison to the curled leaves and blunt fruit peel cracking fruits of the mother plant. Methods: To understand the possible molecular pathways involved, we performed a combined metabolome and transcriptome analysis. Results: We identified 1,060 metabolites in litchi leaves and fruits, of which 106 and 101 were differentially accumulated between the leaves and fruits, respectively. The mutant leaves were richer in carbohydrates, nucleotides, and phenolic acids, while the mother plant was rich in most of the amino acids and derivatives, flavonoids, lipids and organic acids and derivatives, and vitamins. Contrastingly, mutant fruits had higher levels of amino acids and derivatives, carbohydrates and derivatives, and organic acids and derivatives. However, the mother plant's fruits contained higher levels of flavonoids, scopoletin, amines, some amino acids and derivatives, benzamidine, carbohydrates and derivatives, and some organic acids and derivatives. The number of differentially expressed genes was consistent with the metabolome profiles. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway-enriched gene expressions showed consistent profiles as of metabolome analysis. Conclusion: These results provide the groundwork for breeding litchi for fruit and leaf traits that are useful for its taste and yield.

A study on the impact and mechanism of action of public health education on the health of the migrant population: evidence from the 2018 China migrants dynamic survey.

Background: China has the world's largest mobile population. As mobility increases, ensuring the health protection of this population is receiving more attention. Strengthening public health education is a crucial measure to improve their health and achieve equal access to basic public health services in China. Previous research has demonstrated that public health education has an impact on the health of mobile populations. However, there has been limited investigation into the mediating pathways through which health education influences the health of mobile populations, and few studies have examined the heterogeneity of this effect. Objectives: The aim of this study was to analyze the impact of public health education on the health of the mobile population and its mechanism of action. Additionally, we aimed to explore the differences in this impact among different subdivided groups. Methods: This paper analyses the impact of public health education on the health of the mobile population using the 2018 China Migrant Dynamic Survey (CMDS) Data,. The data was cleaned and 4,034 people were included in the analysis. The study employed ordered logistic regression modeling to analyze the mediating pathways through which health education affects health. Additionally, binary logistic regression model, probit model, propensity score matching method and instrumental variables were used to verify the robustness of the results. Results: The self-assessed health status of the mobile population was good, and 82.10% of them accepted public health education. However, 17.89% of the mobile population did not receive any health education. Acceptance of health education can help improve the health status of the mobile population (OR = 1.178, 95% CI = 0.979-1.418). The study found that public health education can positively impact the health of mobile populations by influencing their health and hospitalization behaviors, as well as their social support. The analysis of heterogeneity revealed that the impact of public health education is more significant among rural, middle-aged, low-education, and low-income groups of the mobile population. Conclusion: Public health education can have a positive impact on the health of the migrant populations. To further improve health education for this group, it is necessary to actively promote the establishment of health records for the migrant population, to facilitate the contracting of family doctors by the migrant population, to improve the accessibility to hospitalization services, reduce the burden of hospitalization costs, and enhance social support. Simultaneously, it is essential to offer precise and varied health education to the migrant population based on their characteristics, to promote equity among diverse groups of individuals. These findings not only help to enrich theoretical research on health education for migrant populations and the health of migrant populations but also help to improve the level of public health education for migrant populations and improve the health protection of migrant populations.

Learning Representations from Heart Sound: A Comparative Study on Shallow and Deep Models.

Leveraging the power of artificial intelligence to facilitate an automatic analysis and monitoring of heart sounds has increasingly attracted tremendous efforts in the past decade. Nevertheless, lacking on standard open-access database made it difficult to maintain a sustainable and comparable research before the first release of the PhysioNet CinC Challenge Dataset. However, inconsistent standards on data collection, annotation, and partition are still restraining a fair and efficient comparison between different works. To this line, we introduced and benchmarked a first version of the Heart Sounds Shenzhen (HSS) corpus. Motivated and inspired by the previous works based on HSS, we redefined the tasks and make a comprehensive investigation on shallow and deep models in this study. First, we segmented the heart sound recording into shorter recordings (10 s), which makes it more similar to the human auscultation case. Second, we redefined the classification tasks. Besides using the 3 class categories (normal, moderate, and mild/severe) adopted in HSS, we added a binary classification task in this study, i.e., normal and abnormal. In this work, we provided detailed benchmarks based on both the classic machine learning and the state-of-the-art deep learning technologies, which are reproducible by using open-source toolkits. Last but not least, we analyzed the feature contributions of best performance achieved by the benchmark to make the results more convincing and interpretable.

Spatially resolved single-cell atlas of ascidian endostyle provides insight into the origin of vertebrate pharyngeal organs.

The pharyngeal endoderm, an innovation of deuterostome ancestors, contributes to pharyngeal development by influencing the patterning and differentiation of pharyngeal structures in vertebrates; however, the evolutionary origin of the pharyngeal organs in vertebrates is largely unknown. The endostyle, a distinct pharyngeal organ exclusively present in basal chordates, represents a good model for understanding pharyngeal organ origins. Using Stereo-seq and single-cell RNA sequencing, we constructed aspatially resolved single-cell atlas for the endostyle of the ascidian Styela clava. We determined the cell composition of the hemolymphoid region, which illuminates a mixed ancestral structure for the blood and lymphoid system. In addition, we discovered a cluster of hair cell-like cells in zone 3, which has transcriptomic similarity with the hair cells of the vertebrate acoustico-lateralis system. These findings reshape our understanding of the pharynx of the basal chordate and provide insights into the evolutionary origin of multiplexed pharyngeal organs.

Snail Transcriptionally Represses Brachyury to Promote the Mesenchymal-Epithelial Transition in Ascidian Notochord Cells.

Mesenchymal-epithelial transition (MET) is a widely spread and evolutionarily conserved process across species during development. In Ciona embryogenesis, the notochord cells undergo the transition from the non-polarized mesenchymal state into the polarized endothelial-like state to initiate the lumen formation between adjacent cells. Based on previously screened MET-related transcription factors by ATAC-seq and Smart-Seq of notochord cells, Ciona robusta Snail (Ci-Snail) was selected for its high-level expression during this period. Our current knockout results demonstrated that Ci-Snail was required for notochord cell MET. Importantly, overexpression of the transcription factor Brachyury in notochord cells resulted in a similar phenotype with failure of lumen formation and MET. More interestingly, expression of Ci-Snail in the notochord cells at the late tailbud stage could partially rescue the MET defect caused by Brachyury-overexpression. These results indicated an inverse relationship between Ci-Snail and Brachyury during notochord cell MET, which was verified by RT-qPCR analysis. Moreover, the overexpression of Ci-Snail could significantly inhibit the transcription of Brachyury, and the CUT&Tag-qPCR analysis demonstrated that Ci-Snail is directly bound to the upstream region of Brachyury. In summary, we revealed that Ci-Snail promoted the notochord cell MET and was essential for lumen formation via transcriptionally repressing Brachyury.

FOXO3a Induces Myocardial Fibrosis by Upregulating Mitophagy.

BACKGROUND: Atrial fibrillation is one of the most common cardiac arrhythmias. Myocardial fibrosis is closely associated with atrial remodeling, which leads to heightened risk of atrial fibrillation. This study aimed to explore whether forkhead box protein O3 (FOXO3a) impacts myocardial fibrosis incidence by regulating mitophagy. METHODS: Cell viability was assessed by cell counting kit-8 (CCK-8) assays. The expression of vimentin and cytochrome C was detected by immunofluorescence assays. Quantitative real-time polymerase chain reaction (PCR) was used to analyze the relative mRNA level of FOXO3a. Expression of FOXO3a, phosphorylated FOXO3a, Collagen I, Collagen III, alpha-smooth muscle actin (α-SMA), matrix metalloprotease 9 (MMP9), light chain 3 (LC3), phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1), Parkin, and sequestosome-1 (p62) proteins were determined by western blotting. 5-ethynyl-2'-deoxyuridine (EDU) incorporation was employed to measure cell proliferation. Changes in mitochondrial membrane potential were determined by 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine iodide (JC-1) staining. A wound healing assay was used to examine cell migration, and the levels of reactive oxygen species were determined by flow cytometry. RESULTS: The expression of FOXO3a was upregulated in cardiac fibroblasts treated with angiotensin II (AngII), while the expression of phosphorylated FOXO3a was downregulated under these conditions. FOXO3a knockdown significantly inhibited the proliferation, migration and collagen secretion of cardiac fibroblasts treated with AngII. The ratio of LC3 II/I as well as expression of PINK1 and Parkin was increased, and the expression of p62 was decreased, in cardiac fibroblasts treated with AngII. Moreover, these effects were limited by FOXO3a knockdown. Finally, the mitophagy inducer everolimus (RAD001) attenuated the suppressive effect of FOXO3a knockdown on cardiac fibroblast activation. CONCLUSIONS: FOXO3a promotes the progress of myocardial fibrosis by triggering mitophagy in cardiac fibroblasts.

Tree-shrub-grass composite woodland better facilitates emotional recovery in college students emotion better than other plant communities.

Previous research has indicated that natural landscapes exhibit a greater capacity for ameliorating negative emotional states in individuals when compared to urban landscapes. Nevertheless, significant scientific inquiries, such as the uniformity of the rejuvenating effect across distinct categories of natural landscapes on college students and the choice of the optimal plant community for achieving the most potent restorative effect, remain unexplored. This study aimed to address these questions by selecting four plant communities (single-layer grassland, single-layer woodland, tree-grass composite woodland, tree-shrub-grass composite woodland) and using an electroencephalography method to capture the neuroelectric activity of the participants in combination with the Positive and Negative Affect Schedule score to explore the effects of plant community types on emotional recovery. The results showed that all four plant communities significantly increased positive emotions and significantly reduced negative emotions. There was no significant difference in the recovery effect of positive emotions among the four plant community types, but there was a significant difference in the recovery effect of negative emotions. The effect of tree-shrub-grass composite woodland on the negative emotion recovery effect is the best; the EEG results found that the alpha wave amplitude induced by the tree-shrub-grass composite woodland was significantly higher than that of the other three groups of plant communities, and the EEG and behavioral results were consistent. The results show that the tree-shrub-grass composite woodland has the best restoration effect and has stronger planning and design significance.

RNF20 contributes to epigenetic immunosuppression through CDK9-dependent LSD1 stabilization.

Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcription initiation and is essential for maintaining gene silencing at heterochromatic loci. Inhibition of CDK9 increases sensitivity to immunotherapy, but the underlying mechanism remains unclear. We now report that RNF20 stabilizes LSD1 via K29-mediated ubiquitination, which is dependent on CDK9-mediated phosphorylation. This CDK9- and RNF20-dependent LSD1 stabilization is necessary for the demethylation of histone H3K4, then subsequent repression of endogenous retrovirus, and an interferon response, leading to epigenetic immunosuppression. Moreover, we found that loss of RNF20 sensitizes cancer cells to the immune checkpoint inhibitor anti-PD-1 in vivo and that this effect can be rescued by the expression of ectopic LSD1. Our findings are supported by the observation that RNF20 levels correlate with LSD1 levels in human breast cancer specimens. This study sheds light on the role of RNF20 in CDK9-dependent LSD1 stabilization, which is crucial for epigenetic silencing and immunosuppression. Our findings explore the potential importance of targeting the CDK9-RNF20-LSD1 axis in the development of new cancer therapies.

EM-Trans: Edge-Aware Multimodal Transformer for RGB-D Salient Object Detection.

RGB-D salient object detection (SOD) has gained tremendous attention in recent years. In particular, transformer has been employed and shown great potential. However, existing transformer models usually overlook the vital edge information, which is a major issue restricting the further improvement of SOD accuracy. To this end, we propose a novel edge-aware RGB-D SOD transformer, called, which explicitly models the edge information in a dual-band decomposition framework. Specifically, we employ two parallel decoder networks to learn the high-frequency edge and low-frequency body features from the low-and high-level features extracted from a two-steam multimodal backbone network, respectively. Next, we propose a cross-attention complementarity exploration module to enrich the edge/body features by exploiting the multimodal complementarity information. The refined features are then fed into our proposed color-hint guided fusion module for enhancing the depth feature and fusing the multimodal features. Finally, the resulting features are fused using our deeply supervised progressive fusion module, which progressively integrates edge and body features for predicting saliency maps. Our model explicitly considers the edge information for accurate RGB-D SOD, overcoming the limitations of existing methods and effectively improving the performance. Extensive experiments on benchmark datasets demonstrate that is an effective RGB-D SOD framework that outperforms the current state-of-the-art models, both quantitatively and qualitatively. A further extension to RGB-T SOD demonstrates the promising potential of our model in various kinds of multimodal SOD tasks.

CX­5461 potentiates imatinib­induced apoptosis in K562 cells by stimulating KIF1B expression.

The selective RNA polymerase I inhibitor CX-5461 has been shown to be effective in treating some types of leukemic disorders. Emerging evidence suggests that combined treatments with CX-5461 and other chemotherapeutic agents may achieve enhanced effectiveness as compared with monotherapies. Currently, pharmacodynamic properties of the combination of CX-5461 with tyrosine kinase inhibitors remain to be explored. The present study tested whether CX-5461 could potentiate the effect of imatinib in the human chronic myeloid leukemia cell line K562, which is p53-deficient. It was demonstrated that CX-5461 at 100 nM, which was non-cytotoxic in K562 cells, potentiated the pro-apoptotic effect of imatinib. Mechanistically, the present study identified that the upregulated expression of kinesin family member 1B (KIF1B) gene might be involved in mediating the pro-apoptotic effect of imatinib/CX-5461 combination. Under the present experimental settings, however, neither CX-5461 nor imatinib alone exhibited a significant effect on KIF1B expression. Moreover, using other leukemic cell lines, it was demonstrated that regulation of KIF1B expression by imatinib/CX-5461 was not a ubiquitous phenomenon in leukemic cells and should be studied in a cell type-specific manner. In conclusion, the results suggested that the synergistic interaction between CX-5461 and imatinib may be of potential clinical value for the treatment of tyrosine kinase inhibitor-resistant chronic myeloid leukemia.

Digital image correlation-assisted phase-sensitive optical coherence tomography.

In this Letter, we introduce a digital image correlation-assisted (DIC-assisted) method to tackle the challenges of phase decorrelation and the inability to measure lateral displacement in phase-sensitive optical coherence tomography (PhS-OCT). This DIC-assisted PhS-OCT (DIC-PhS-OCT) first employs DIC to track displacements from the measured amplitude spectra and subsequently uses these tracked displacements to correct supra-pixel displacement offsets in the measured phase spectra. As a result, it effectively mitigates phase decorrelation resulting from both axial and lateral displacements while enabling the acquisition of sub-pixel-level lateral displacements during the DIC computation. Our experiments demonstrate the effectiveness of DIC-PhS-OCT in addressing these challenges while retaining the ultrahigh sensitivity of conventional PhS-OCT.