Theoretical Insights into the Effect of Different Numbers of Thiophene Groups on Hydrogen Bond Interaction and Excited-State Intramolecular Proton-Transfer Process for Flavonoid Derivatives.

In this study, we systematically explored the impact of varying the number of thiophene groups on the hydrogen bond interaction and excited-state intramolecular proton-transfer (ESIPT) processes in flavonoid derivatives (STF, DTF, and TTF) using the density functional theory and time-dependent density functional theory methods. Initially, a thorough analysis of the optimized geometric structures revealed that the intramolecular hydrogen bond in the S1 state is enhanced and gradually weakened as the number of thiophene groups increases. To gain a deeper understanding of the hydrogen bond interaction, topological analysis, interaction region indicator scatter plots, and isosurface plots were employed. These images provide further insights that align with the structural analysis. Additionally, we observed a red-shift in the electronic spectra (absorption and fluorescence spectra), which is primarily attributed to the narrowing of the energy gap between the highest occupied molecular orbital and the lowest unoccupied molecular orbital, as elucidated by the frontier molecular orbitals. Furthermore, a combined analysis between the hole-electron distribution and the transition density matrix heat map shows that electron excitation involves the unidirectional charge-transfer mechanism. In the end, by conducting relaxed potential energy curve scans, we found that an increase in the number of thiophene groups elevates the energy barrier for ESIPT, making it more challenging for the reaction. In summary, our study underscores the vital effect of thiophene-substituted numbers in modulating the ESIPT process, which is able to provide valuable insights for the design and synthesis of desired organic fluorescent probes in the future.

Generation of allogeneic CAR-NKT cells from hematopoietic stem and progenitor cells using a clinically guided culture method.

Cancer immunotherapy with autologous chimeric antigen receptor (CAR) T cells faces challenges in manufacturing and patient selection that could be avoided by using 'off-the-shelf' products, such as allogeneic CAR natural killer T (AlloCAR-NKT) cells. Previously, we reported a system for differentiating human hematopoietic stem and progenitor cells into AlloCAR-NKT cells, but the use of three-dimensional culture and xenogeneic feeders precluded its clinical application. Here we describe a clinically guided method to differentiate and expand IL-15-enhanced AlloCAR-NKT cells with high yield and purity. We generated AlloCAR-NKT cells targeting seven cancers and, in a multiple myeloma model, demonstrated their antitumor efficacy, expansion and persistence. The cells also selectively depleted immunosuppressive cells in the tumor microenviroment and antagonized tumor immune evasion via triple targeting of CAR, TCR and NK receptors. They exhibited a stable hypoimmunogenic phenotype associated with epigenetic and signaling regulation and did not induce detectable graft versus host disease or cytokine release syndrome. These properties of AlloCAR-NKT cells support their potential for clinical translation.

Influence of atomic electronegativity on ESIPT behaviour for the BTDI and its derivatives: Theoretical exploration.

In this work, we theoretically explored the influence of atomic electronegativity on excited-state intramolecular proton transfer (ESIPT) behavior among novel fluorescent probes BTDI and its derivatives (BODI and BSeDI). A thorough examination of the optimized structural parameters and infrared vibrational spectra reveals an enhancement in intramolecular hydrogen bonding within BTDI and its derivatives upon light excitation. This finding is further reinforced by topological analysis and interaction region indicator scatter plots, which underscores the sensitivity of atomic electronegativity to variations in hydrogen bonding strength. With regards to absorption and fluorescence spectra, the decrease in atomic electronegativity leads to a pronounced redshift, primarily attributed to the narrowing of the energy gap. Additionally, an analysis of potential energy curves and the exploration of intrinsic reaction coordinate paths based on transition state structures afford a deeper understanding of the mechanism underlying ESIPT and being modulated through the manipulation of atomic electronegativity. We anticipate that this work on atomic electronegativity regulating ESIPT behavior will serve as a catalyst for novel fluorescent probes in the future, offering fresh perspectives and insights.

The effect of liver metastases on clinical efficacy of first-line programmed death-1 inhibitor plus chemotherapy in esophageal squamous cell carcinoma: A post hoc analysis of ASTRUM-007 and meta-analysis.

OBJECTIVE: To explore the efficacy of serplulimab plus chemotherapy in esophageal squamous cell carcinoma (ESCC) patients with liver metastases. METHODS: A post hoc exploratory analysis of ASTRUM-007 study was performed, focusing on the association between the liver metastases status and the clinical outcomes. A systematic literature search of electronic databases was conducted to identify eligible randomized controlled trials for the meta-analysis. Study-level pooled analyses of hazard ratios (HRs) for PFS according to liver metastases were performed. RESULTS: The post hoc analysis of ASTRUM-007 showed that although patients with liver metastases had a worse prognosis comparing with the non-liver metastases patients in both treatment arms (serplulimab plus chemotherapy arm: median PFS, 5.7 vs. 6.6 months, HR 1.57 [95% CI, 1.15-2.13]; median OS, 13.7 vs. 15.3 months, HR 1.48 [95% CI, 1.09-1.98]; placebo plus chemotherapy arm: median PFS, 4.3 vs. 5.5 months, HR 1.58 [95% CI, 1.01-2.39]; median OS, 10.3 vs. 11.2 months, HR 1.32 [95% CI, 0.84-2.00]), OS and PFS benefits derived from serplulimab plus chemotherapy versus placebo plus chemotherapy in this study were observed in both patients with liver metastases (HR of PFS: 0.60; 95% CI, 0.37-0.97; HR of OS: 0.68; 95% CI, 0.43-1.11) and the non-liver metastases patients (HR of PFS: 0.62; 95% CI, 0.49-0.80; HR of OS: 0.69; 95% CI, 0.55-0.87) with similar magnitude. Three randomized controlled trials were included in the meta-analysis. Pooled HRs demonstrated that the addition of anti-PD-1 antibodies significantly improved PFS compared to chemotherapy alone regardless of liver metastases status. CONCLUSIONS: This study reveals that the presence of liver metastases is a poor prognostic factor but does not affect the improvements in both PFS and OS brought by adding PD-1 blockade to chemotherapy in ESCC patients. Predictive biomarkers for survival in these patients warrant further investigation.

Assessing Patterns of CGM use and Metrics of Glycemic Control in T1D and T2D Patients in the Veterans Healthcare System: Integrating CGM Device Data with EHR Data.

OBJECTIVE: To integrate long-term daily continuous glucose monitoring (CGM) device data with electronic health records (EHR) for type 1 and type 2 diabetes patients in the Veterans Affairs Healthcare System to assess real-world patterns of CGM use and the reliability of EHR-based CGM information. RESEARCH DESIGN AND METHODS: This observational study used Dexcom CGM device data linked with EHR (from 2015-2020) for a large national cohort of diabetes patients. We tracked the initiation and consistency of CGM use, assessed concordance of CGM use and measures of glucose control between CGM device data and EHR records, and examined results by age, ethnicity, and diabetes type. RESULTS: The time from pharmacy release of CGM to patients to initiation of uploading CGM data to Dexcom servers averaged three weeks but demonstrated wide variation among individuals; importantly, this delay decreased markedly over the later years. The average daily wear time of CGM exceeded 22 hours over nearly three years of follow-up. Patterns of CGM use were generally consistent across age, race/ethnicity groups and diabetes type. There was strong concordance between EHR-based estimates of CGM use and Dexcom CGM wear time and between estimates of glucose control from both sources. CONCLUSIONS: The study demonstrates our ability to reliably integrate CGM devices and EHR data to provide valuable insights into CGM use patterns. The results indicate in the real-world environment that CGM is worn consistently over many years for both type 1 and type 2 patients within the Veterans Affairs Healthcare System and is similar across major race/ethnicity and age groups.

Revealing mechanism of phenolic-amine reaction to form humus in compost based on high-resolution liquid chromatography mass spectrometry and spectroscopy.

Humus is the stable form of carbon storage in straw compost. The phenolic-amine reaction is a pathway for humus formation in straw compost. In this study, two reaction systems, GP group (pyrogallol and glycine) and GCP group (catechol, pyrogallol, and glycine), were constructed in a simulated composting environment and revealed the molecular binding mechanism of the phenolic-amine reaction through spectroscopy and mass spectrometry. The results showed that phenolic self-polymerization was faster than phenolic-amine reaction. Therefore, the aromatization degree of GP was 27.14 % higher than that of GCP. The phenolic-amine reaction first produced fulvic acid, and then formed humus units rich in active functional group structures (i.e., phenolic hydroxyl and carboxyl groups). These units further captured small molecule compounds to eventually form humic acid. This study would provide theoretical support for exploring the humus formation process and the promotion of the straw humification by adding phenol or amino acids to compost.

Construction of cellulose-based hybrid hydrogel beads containing carbon dots and their high performance in the adsorption and detection of mercury ions in water.

Cellulose-based adsorbents have been extensively developed in heavy metal capture and wastewater treatment. However, most of the reported powder adsorbents suffer from the difficulties in recycling due to their small sizes and limitations in detecting the targets for the lack of sensitive sensor moieties in the structure. Accordingly, carbon dots (CDs) were proposed to be encapsulated in cellulosic hydrogel beads to realize the simultaneous detection and adsorption of Hg (II) in water due to their excellent fluorescence sensing performance. Besides, the molding of cellulose was beneficial to its recycling and further reduced the potential environmental risk generated by secondary pollution caused by adsorbent decomposition. In addition, the detection limit of the hydrogel beads towards Hg (II) reached as low as 8.8 × 10-8 M, which was below the mercury effluent standard declared by WHO, exhibiting excellent practicability in Hg (II) detection and water treatment. The maximum adsorption capacity of CB-50 % for Hg (II) was 290.70 mg/g. Moreover, the adsorbent materials also had preeminent stability that the hydrogel beads could maintain sensitive and selective sensing performance towards Hg (II) after 2 months of storage. Additionally, only 3.3% of the CDs leaked out after 2 weeks of immersion in water, ensuring the accuracy of Hg (II) evaluation. Notably, the adsorbent retained over 80% of its original adsorption capacity after five consecutive regeneration cycles, underscoring its robustness and potential for sustainable environmental applications.

Abietane diterpenoids from Caryopteris incana (Thunb.) Miq. And their HIF-2α inhibitory activities in vitro.

Eleven previously undescribed abietane-type diterpenoids, named caryopincanoids A-K (1-11), together with five known compounds, were isolated from the EtOH extract of the aerial parts of Caryopteris incana (Thunb.) Miq. Their structures were elucidated on the basis of comprehensive spectroscopic data, NMR calculations, and ECD calculations. The inhibitory activities of all compounds against HIF-2α gene expression in 786-O cells were tested by luciferase assay. Compounds 7, 9, 15, and 16 showed significant inhibitory effects with IC50 values ranging from 12.73 to 23.80 µM. The preliminary structure-activity relationship of these compounds was also discussed.

Standardization of ultrasound images across various centers: M2O-DiffGAN bridging the gaps among unpaired multi-domain ultrasound images.

Domain shift problem is commonplace for ultrasound image analysis due to difference imaging setting and diverse medical centers, which lead to poor generalizability of deep learning-based methods. Multi-Source Domain Transformation (MSDT) provides a promising way to tackle the performance degeneration caused by the domain shift, which is more practical and challenging compared to conventional single-source transformation tasks. An effective unsupervised domain combination strategy is highly required to handle multiple domains without annotations. Fidelity and quality of generated images are also important to ensure the accuracy of computer-aided diagnosis. However, existing MSDT approaches underperform in above two areas. In this paper, an efficient domain transformation model named M2O-DiffGAN is introduced to achieve a unified mapping from multiple unlabeled source domains to the target domain. A cycle-consistent "many-to-one" adversarial learning architecture is introduced to model various unlabeled domains jointly. A condition adversarial diffusion process is employed to generate images with high-fidelity, combining an adversarial projector to capture reverse transition probabilities over large step sizes for accelerating sampling. Considering the limited perceptual information of ultrasound images, an ultrasound-specific content loss helps to capture more perceptual features for synthesizing high-quality ultrasound images. Massive comparisons on six clinical datasets covering thyroid, carotid and breast demonstrate the superiority of the M2O-DiffGAN in the performance of bridging the domain gaps and enlarging the generalization of downstream analysis methods compared to state-of-the-art algorithms. It improves the mean MI, Bhattacharyya Coefficient, dice and IoU assessments by 0.390, 0.120, 0.245 and 0.250, presenting promising clinical applications.

Construction and validation of "WCH-nomogram" for predicting the prognosis after resection of colorectal liver metastases.

BACKGROUND: The prognostic predictive tool for patients with colorectal liver metastasis (CRLM) is limited and the criteria for administering preoperative neoadjuvant chemotherapy in CRLM patients remain controversial. METHODS: This study enrolled 532 CRLM patients at West China Hospital (WCH) from January 2009 to December 2019. Prognostic factors were identified from the training cohort to construct a WCH-nomogram and evaluating accuracy in the validation cohort. Receiver operating characteristic (ROC) curve analysis was used to compare the prediction accuracy with other existing prediction tools. RESULTS: From the analysis of the training cohort, four independent prognostic risk factors, namely tumor marker score, KRAS mutation, primary lymph node metastasis, and tumor burden score were identified on which a WCH-nomogram was constructed. The C-index of the two cohorts were 0.674 (95% CI: 0.634-0.713) and 0.655 (95% CI: 0.586-0.723), respectively, which was better than the previously reported predication scores (CRS, m-CS and GAME score). ROC curves showed AUCs for predicting 1-, 3-, and 5-year overall survival (OS) of 0.758, 0.709, and 0.717 in the training cohort, and 0.860, 0.669, and 0.692 in the validation cohort, respectively. A cutoff value of 114.5 points was obtained for the WCH-nomogram total score based on the maximum Youden index of the ROC curve of 5-year OS. Risk stratification showed significantly better prognosis in the low-risk group, however, the high-risk group was more likely to benefit from neoadjuvant chemotherapy. CONCLUSIONS: The WCH-nomogram demonstrates superior prognostic stratification compared to prior scoring systems, effectively identifying CRLM patients who may benefit the most from neoadjuvant chemotherapy.

Ag-modified enhance the performances of ZnO@CFs based omnidirectional photoelectrochemical ultraviolet detectors.

There are several prospective applications for omnidirectional ultraviolet (UV) detectors and underwater detection detectors in optical systems and optical fields. In this work, ZnO nanorods arrays were grown on carbon fibers (CFs). An appropriate amount of Ag nanoparticles (NPs) was deposited on the surface of ZnO nanorods by photochemical deposition. This improved the performance of photoelectrochemical (PEC) based UV detectors. Under 365 nm and 10 mW cm-2 UV irradiation, the photocurrent density of the 30s-Ag/ZnO@CFs based PEC UV detector can reach 1.28 mA cm-2, which is about 7 times that of the ZnO@CFs based PEC UV detector, and the rising time is shortened from 0.17 s to 0.10 s. The reason is that increased absorption of ultraviolet light induced by the localized surface plasmon resonance. In addition, the detector exhibits a good flexibility and remains flexible after hundreds of bends and twists. Moreover, the detector is responsive in the range of rotation angle from 0 to 360°. It provides an insight to improve the photoelectric performance and underwater omnidirectional detection ability of the PEC UV detector.

A novel dual near-infrared fluorescent probe for bioimaging and visualization of viscosity in acute alcoholic liver injury.

A dual NIR fluorescent probe Cy-ND is developed for viscosity sensing with λex/em = 766/806 nm, making it apt for biological analysis, whose response is validated through DFT and TDDFT computations. Cy-ND successfully detected viscosity changes amidst acute alcohol-induced liver injury and liver ischemia-reperfusion injury.

PSAEEGNet: pyramid squeeze attention mechanism-based CNN for single-trial EEG classification in RSVP task.

Introduction: Accurate classification of single-trial electroencephalogram (EEG) is crucial for EEG-based target image recognition in rapid serial visual presentation (RSVP) tasks. P300 is an important component of a single-trial EEG for RSVP tasks. However, single-trial EEG are usually characterized by low signal-to-noise ratio and limited sample sizes. Methods: Given these challenges, it is necessary to optimize existing convolutional neural networks (CNNs) to improve the performance of P300 classification. The proposed CNN model called PSAEEGNet, integrates standard convolutional layers, pyramid squeeze attention (PSA) modules, and deep convolutional layers. This approach arises the extraction of temporal and spatial features of the P300 to a finer granularity level. Results: Compared with several existing single-trial EEG classification methods for RSVP tasks, the proposed model shows significantly improved performance. The mean true positive rate for PSAEEGNet is 0.7949, and the mean area under the receiver operating characteristic curve (AUC) is 0.9341 (p < 0.05). Discussion: These results suggest that the proposed model effectively extracts features from both temporal and spatial dimensions of P300, leading to a more accurate classification of single-trial EEG during RSVP tasks. Therefore, this model has the potential to significantly enhance the performance of target recognition systems based on EEG, contributing to the advancement and practical implementation of target recognition in this field.

Fabrication of SERS composite substrates using Ag nanotriangles-modified SiO2 photonic crystal and the application of malachite green detection.

A novel surface-enhanced Raman scattering (SERS) composite substrates on the basis of Ag triangular nanoplates(Ag TNPs)-modified SiO2 photonic crystals (PC) is fabricated and applied to the SERS detection of malachite green (MG). It consists of uniformly arranged Ag TNP@SiO2, a new PC. Notably, Ag TNP are uniformly aligned on the SiO2 surface, forming a three-dimensional high-density hotspot nanostructure. With the tip "hot spots" of Ag TNPs, Bragg diffraction of SiO2 and coupling enhancement between Ag TNPs and SiO2, the SERS enhancement of this composite substrates was multiplied. The effect on the SERS of Ag TNP@SiO2 composite substrate was systematically optimized by tuning Ag TNP size, size of SiO2 microspheres, coverage of Ag TNPs on SiO2 and fabrication method of Ag TNPs and PC. Moreover, the uniform of SERS composite substrates and Raman signal was dramatically increased by the method of vertical deposition. Eventually, the SERS composite substrates were employed in MG detection. Its broad detection range of 1 pM-1 µM and low limit of detection (LOD) of 0.49 pM indicated acceptable sensitivity and repeatability. This work illustrates the promising applicability in food safety analysis based on SERS composite substrates composed by Ag TNP@SiO2 with numerous SERS enhancements and excellent stability.

Exosomes derived from HUVECs alleviate ischemia-reperfusion induced inflammation in neural cells by upregulating KLF14 expression.

Neuroinflammation plays a key role in the progression of secondary brain injury after ischemic stroke, and exosomes have been increasingly recognized to eliminate inflammatory responses through various mechanisms. This study aimed to explore the effect and possible mechanism of human umbilical vein endothelial cells derived exosomes (H-EXOs) on neuroinflammation. We established a transient middle cerebral artery occlusion/reperfusion (tMCAO/R) in male rats and oxygen-glucose-deprivation/reoxygenation (OGD/R) model in cultured neurons to mimic secondary brain injury after ischemic stroke in vivo. H-EXOs were administered at the same time of reperfusion. Results showed that the production of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6, and the transcription factor Krüppel-like factor 14 (KLF14) were significantly increased both in rat brain tissue and cultured neural cells after ischemic-reperfusion (I/R) injury. H-EXOs treatment significantly improved the cultured cell viability, reduced infarct sizes, mitigated neurobehavioral defects, and alleviated the expression of pro-inflammatory cytokines compared with the control group, indicating that H-EXOs exerted anti-inflammatory effect against I/R injury. Further studies revealed that the anti-inflammatory effect of H-EXOs could be weakened by small-interfering RNA (siKLF4) transfection. KLF14 was a protective factor produced during cerebral ischemia-reperfusion injury. In conclusion, H-EXOs protect neurons from inflammation after I/R injury by enhancing KLF14 expression.

Association between Body Iron Status and Cognitive Task Performance in a Nationally Representative Sample of Older Adults.

Iron is an essential micronutrient that is necessary for proper cognitive function. However, the dose-response relationship between body iron status and cognitive function remains unclear. The objective of this study was to investigate the association between serum ferritin concentrations, an indicator of body iron status, and cognitive function in older adults. Based on the National Health and Nutrition Examination Survey (NHANES) 1999 -2002 in the United States, nationally representative data was collected from 2,567 adults aged 60 years and older who had objectively measured serum ferritin levels and cognitive performance. High ferritin levels were defined as a serum ferritin level >200 ng/mL in women and >300 ng/mL in men. Low ferritin levels were defined as a serum ferritin level <30 ng/mL. The digit symbol substitution test (DSST) was employed to assess cognitive function. Multivariable logistic regression analyses with survey weights were performed after the DSST was dichotomized at the median score. The weighted prevalence of adults with normal, low, and high serum ferritin levels were 73.98%, 9.12%, and 16.91%, respectively. A U-shaped association between serum ferritin concentrations and cognitive task performance was observed. After adjusting for demographic, socioeconomic, lifestyle, and C-reactive protein factors, the odds ratio (95% confidence intervals) for lower cognitive performance was 1.39 (1.11, 1.74) in adults with high ferritin levels and 1.38 (0.86, 2.22) in adults with low ferritin levels, compared with those with normal ferritin levels. The association between serum ferritin levels and lower cognitive performance was stronger in adults aged 60 to 69 years old than those aged 70 years and older. In conclusion, in a nationally representative sample of older adults in the United States, a high serum ferritin level was significantly associated with worse cognitive task performance. Thus, the relationship between low serum ferritin concentrations and cognitive task performance warrants further investigation.

Palladium-Catalyzed Ligand-Controlled Switchable Hetero-(5 + 3)/Enantioselective [2σ+2σ] Cycloadditions of Bicyclobutanes with Vinyl Oxiranes.

For nearly 60 years, significant research efforts have been focused on developing strategies for the cycloaddition of bicyclobutanes (BCBs). However, higher-order cycloaddition and catalytic asymmetric cycloaddition of BCBs have been long-standing formidable challenges. Here, we report Pd-catalyzed ligand-controlled, tunable cycloadditions for the divergent synthesis of bridged bicyclic frameworks. The dppb ligand facilitates the formal (5+3) cycloaddition of BCBs and vinyl oxiranes, yielding valuable eight-membered ethers with bridged bicyclic scaffolds in 100% regioselectivity. The Cy-DPEphos ligand promotes selective hetero-[2σ+2σ] cycloadditions to access pharmacologically important 2-oxabicyclo[3.1.1]heptane (O-BCHeps). Furthermore, the corresponding catalytic asymmetric synthesis of O-BCHeps with 94-99% ee has been achieved using chiral (S)-DTBM-Segphos, representing the first catalytic asymmetric cross-dimerization of two strained rings. The obtained O-BCHeps are promising bioisosteres for ortho-substituted benzenes.

METTL3-mediated m6A methylation of DNMT1 promotes the progression of non-small cell lung cancer by regulating the DNA methylation of FOXO3a.

Background: The aim of this study was to investigate the effect of DNA methylation of Fork Head Box O3 (FOXO3a) on the process of epithelial-mesenchymal transition (EMT) in non-small cell lung cancer (NSCLC). Methods: The expressions of FOXO3a, DNA methyltransferase 1 (DNMT1), METTL3, and EMT-related proteins (E-cadherin and N-cadherin) were measured. The influence of 5-Aza-dC and DNMT1 on the methylation level in the promoter region of FOXO3a was examined through the application of methylation-specific PCR (MSP). Chromatin immunoprecipitation (ChIP) was employed to detect binding between DNMT1 and the FOXO3a promoter. Methylated RNA immunoprecipitation (MeRIP) was utilized to evaluate the level of DNMT1 N6-methyladenosine (m6A) methylation. The assessment of cell viability and invasion abilities of A549 cells was performed using Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. NSCLC xenograft mouse models were established by subcutaneously injected treated A549 cells into nude mice. Results: The expression levels of DNMT1 and DNA methylation level FOXO3a were found to be significantly increased, whereas FOXO3a expression was considerably decreased in NSCLC cell lines and NSCLC tumor tissues. Both 5-Aza-dC treatment and DNMT1 knockdown resulted in the down-regulation of DNA methylation levels of FOXO3a while simultaneously up-regulating the expression of FOXO3a. A ChIP assay demonstrated that DNMT1 has the ability to bind to the promoter region of FOXO3a. Furthermore, the knockdown of DNMT1 promoted E-cadherin expression, but inhibited expression of N-cadherin, cell viability, and invasion ability. However, the knockdown of FOXO3a hindered the effect of DNMT1 knockdown on EMT, cell viability, and invasion ability of A549 cells. This was evidenced by decreased E-cadherin expression and increased N-cadherin expression, as well as increased cell viability and invasion ability. Increased expression of DNMT1 resulted from m6A methylation of DNMT1, which was mediated by METTL3. Overexpression of DNMT1 decreased of E-cadherin expression while increased N-cadherin expression, cell viability, and invasion ability in METTL3-shRNA treated A549 cells. In xenograft mouse models, DNMT1 knockdown significantly reduced tumor volumes and tumor weight. DNMT1 knockdown upregulated the expression of FOXO3a and E-cadherin, while downregulated N-cadherin expression in vivo. Conclusion: METTL3-mediated m6A methylation of DNMT1 up-regulates FOXO3a promoter methylation, thereby promoting the progression of NSCLC.

Health Status of Nonemergency Patients in the Emergency Department Using the EQ-5D.

Background: Emergency department (ED) overcrowding is influenced by several factors including the hospital's capacity, staff, patient discharges, and community resources. The number of annual ED visits has increased, with patients' medical needs exceeding emergency capacity, resulting in a widespread concern about emergency room overcrowding. Nonemergency patients tend to use large amounts of emergency medical resources, which is one reason for ED overcrowding. Most patients consider their medical cases urgent, whereas medical professionals consider many cases to be nonemergency. Only a few studies have examined self-rated health among nonemergency patients. Methods: This cross-sectional study was conducted in the ED of a tertiary hospital in China using the European Quality of Life Five-Dimensional Questionnaire to investigate the health status of nonemergency patients. Results: Among the 545 respondents, 246 (45.14%) self-assessed their health as excellent, 186 (34.13%) as very good, 70 (12.84%) as good, 32 (5.87%) as average, and 11 (2.02%) as poor. Problems related to pain/discomfort were reported by 317 (58.17%) participants, 214 (39.27%) responded that they had problems related to daily activities, 212 (38.90%) responded that they felt anxious or depressed, 211 (38.35%) responded that they had problems related to self-care, and some or extreme problems related to mobility were stated by 193 people (35.41%). Conclusions: Nonemergency patients generally reported good health. Pain/discomfort was the most significant factor affecting the health of nonemergency patients, followed by limitation of daily activities. The duration of illness onset and self-rated health status were common factors influencing the health status of nonemergency patients. This trial is registered with ChiCTR1900023578.