Mechanisms insights into Cd passivation in soil by lignin biochar: Transition from flooding to natural air-drying.

Biochar shows great potential in soil cadmium pollution treatment, however, the effect and mechanisms of biochar on cadmium passivation (CP) during the long-term process of soil from flooding to natural air-drying are not clear. In this study, a 300-day experiment was conducted to keep the flooded water level constant for the first 100 days and then dried naturally. Mechanisms of CP by lignin biochar (LBC) were analyzed through chemical analysis, FTIR-2D-COS, EEMs-PARAFAC, ultraviolet spectroscopy characterizations, and microbial community distribution of soil. Results showed that application of LBC results in rapid CP ratio in soil within 35 days, mainly in the residual and Fe-Mn bound states (total 72.80%). CP ratio further increased to 90.89% with water evaporation. The CP mechanisms include precipitation, electrostatic effect, humus complexation, and microbial remediation by promoting the propagation of fungi such as Penicillium and Trichoderma. Evaporation of water promoted the colonization of aerobic microorganisms and then increased the degree of soil humification and aromatization, thereby enhancing the cadmium passivation. Simultaneously, the biochar could reduce the relative abundance of plant pathogens in soil from 1.8% to 0.03% and the freshness index (ß/α) from 0.64 to 0.16, favoring crop growth and promoting carbon sequestration and emission reduction.

Ezrin Contributes to the Damage of Airway Epithelial Barrier Related to Diabetes Mellitus.

Background: Diabetes mellitus predisposes individuals to respiratory infections. The airway epithelial barrier provides defense against inhaled antigens and pathogens. Ezrin, is a component of the membrane-cytoskeleton that maintains the cellular morphology, intercellular adhesion, and barrier function of epithelial cells. This study aimed to explore the role of ezrin in airway epithelial barrier damage and correlate its expression and activation with diabetes mellitus. Methods: This study was performed in a murine model of diabetes mellitus and with human bronchial epithelial BEAS-2B cells using real-time PCR, Western blotting, immunohistochemical and immunofluorescence staining. Ezrin was knocked down in BEAS-2B cells using siRNA. Ezrin phosphorylation levels were measured to determine activation status. The integrity of the airway epithelial barrier was assessed in vivo by characterizing morphological structure, and in vitro in BEAS-2B cells by measuring tight junction protein expression, transepithelial electrical resistance (TER) and permeability. Results: We demonstrated that ezrin expression levels were lower in the lung tissue and airway epithelium of diabetic mice than those in control mice. The morphological structure of the airway epithelium was altered in diabetic mice. High glucose levels downregulated the expression and distribution of ezrin and connexin 43, reduced the expression of tight junction proteins, and altered the epithelial barrier characteristics of BEAS-2B cells. Ezrin knockdown had effects similar to those of high glucose levels. Moreover, a specific inhibitor of ezrin Thr567 phosphorylation (NSC305787) inhibited epithelial barrier formation. Conclusion: These results demonstrate that ezrin expression and activation are associated with airway epithelial damage in diabetes mellitus. These findings provide new insights into the molecular pathogenesis of pulmonary infections in diabetes mellitus and may lead to novel therapeutic interventions for airway epithelial barrier damage.

Brain activation and connection across resting and motor-task states in patients with generalized tonic-clonic seizures.

AIMS: Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor execution condition, which might provide novel insight into the pathomechanism. METHODS: Resting-state and motor-task fMRI data were collected from 50 patients with GTCS, including 18 patients newly diagnosed without antiepileptic drugs (ND_GTCS) and 32 patients receiving antiepileptic drugs (AEDs_GTCS). Motor activation and its association with head motion and cerebral gradients were assessed. Whole-brain network connectivity across resting and motor states was further calculated and compared between groups. RESULTS: All patients showed over-activation in the postcentral gyrus and the ND_GTCS showed decreased activation in putamen. Specifically, activation maps of ND_GTCS showed an abnormal correlation with head motion and cerebral gradient. Moreover, we detected altered functional network connectivity in patients within states and across resting and motor states by using repeated-measures analysis of variance. Patients did not show abnormal connectivity in the resting state, while distributed abnormal connectivity in the motor-task state. Decreased across-state network connectivity was also found in all patients. CONCLUSION: Convergent findings suggested the over-response of activation and connection of the brain to motor execution in GTCS, providing new clues to uncover motor susceptibility underlying the disease.

SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors.

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor progression. However, the precise molecular mechanisms governing the nuclear import of YAP are not fully understood. In this study, we have uncovered a crucial role of SOX9 in the activation of YAP. SOX9 promotes the nuclear translocation of YAP by direct interaction. Importantly, we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of YAP. Additionally, we have discovered a novel asymmetrical dimethylation of YAP at Arg-124 (YAP-R124me2a) catalyzed by PRMT1. YAP-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple cancers. Furthermore, we disrupted the interaction between SOX9 and YAP using a competitive peptide, S-A1, which mimics an α-helix of SOX9 containing Asp-125. S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor growth. This study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.

A new model for dynamic mapping of effective connectivity in task fMRI.

Whole-brain dynamic functional connectivity is a growing area in neuroimaging research, encompassing data-driven methods for investigating how large-scale brain networks dynamically reorganize during resting states. However, this approach has been rarely applied to functional magnetic resonance imaging (fMRI) data acquired during task performance. In this study, we first combined the psychophysiological interactions (PPI) and sliding-window methods to analyze dynamic effective connectivity of fMRI data obtained from subjects performing the N-back task within the Human Connectome Project dataset. We then proposed a hypothetical model called Condition Activated Specific Trajectory (CAST) to represent a series of spatiotemporal synchronous changes in significantly activated connections across time windows, which we refer to as a trajectory. Our finding demonstrate that the CAST model outperforms other models in terms of intra-group consistency of individual spatial pattern of PPI connectivity, overall representational ability of temporal variability and hierarchy for individual task performance and cognitive traits. This dynamic view afforded by the CAST model reflects the intrinsic nature of coherent brain activities.

Association between abusive supervision and nurses' withholding voice about patient safety: the roles of impression management motivation and speak up-related climate.

BACKGROUND: Abusive supervision by the nurse manager significantly influences nurses' withholding voice about patient safety. The role of impression management motivation and speak up-related climate is crucial in understanding their connection. This study aimed to explore the relationship between abusive supervision, impression management motivation, speak up-related climate, and withholding voice about patient safety. METHODS: This cross-sectional study employed a convenience sampling method to recruit 419 clinical nurses from Taizhou Hospital, Zhejiang Province, China, between 1 November 2022 and 31 January 2023. The study adhered to the STROBE checklist. Abusive supervision and impression management motivation were assessed using the Chinese versions of the Abusive Supervision Scale and the Impression Management Motivation Scale, respectively. Withholding voice about patient safety and speak up-related climate were identified using the Chinese version of the Speaking Up about Patient Safety Questionnaire. RESULTS: Nurse leaders' abusive supervision (ß=0.40, p<0.01) and nurses' impression management motivation (ß=0.10, p<0.01) significantly and positively influenced nurses' withholding voice about patient safety. We introduced impression management motivation as a mediating variable, and the effect of abusive supervision on nurses' withholding voice decreased (ß from 0.40 to 0.38, p< 0.01). Nurses' speak up-related climate played a moderating role between abusive supervision and impression management motivation (ß= 0.24, p<0.05). CONCLUSIONS: Abusive supervision by nursing leaders can result in nurses withholding voice about patient safety out of self-protective impression management motives. This phenomenon inhibits nurses' subjective initiative and undermines their proactive involvement in improving patient safety, and hinders the cultivation of a culture encouraging full participation in patient safety, which should warrant significant attention.

Abnormal functional connectivity of white-matter networks and gray-white matter functional networks in patients with NMOSD.

Cognitive impairment (CI) has been reported in 29-70% of patients with neuromyelitis optica spectrum disorder (NMOSD). Abnormal white matter (WM) functional networks that correlate with cognitive functions have not been studied well in patients with NMOSD. The aim of the current study was to investigate functional connectivity (FC), spontaneous activity, and functional covariance connectivity (FCC) abnormalities of WM functional networks in patients with NMOSD and their correlation with cognitive performance. Twenty-four patients with NMOSD and 24 healthy controls (HCs) were included in the study. Participants underwent brain resting-state functional magnetic resonance imaging (fMRI) and the Montreal Cognitive Assessment (MoCA). Eight WM networks and nine gray matter (GM) networks were created. In patients, WM networks, including WM1-4, WM1-8, WM2-6, WM2-7, WM2-8, WM4-8, WM5-8 showed reduced FC (P < 0.05). All WM networks except WM1 showed decreased spontaneous activity (P < 0.05). The major GM networks demonstrated increased/decreased FC (P < 0.05), whereas GM7-WM7, GM8-WM4, GM8-WM6 and GM8-WM8 displayed decreased FC (P < 0.05). The MoCA results showed that two-thirds (16/24) of the patients had CI. FC and FCC in WM networks were correlated negatively with the MoCA scores (P < 0.05). WM functional networks are multi-layered. Abnormal FC of WM functional networks and GM functional networks may be responsible for CI.

Development of (2-(Benzyloxy)phenyl)methanamine Derivatives as Potent and Selective Inhibitors of CARM1 for the Treatment of Melanoma.

Coactivator-associated arginine methyltransferase 1 (CARM1), an important member of type I protein arginine methyltransferases (PRMTs), has emerged as a promising therapeutic target for various cancer types. In our previous study, we have identified a series of type I PRMT inhibitors, among which ZL-28-6 (6) exhibited increased activity against CARM1 while displaying decreased potency against other type I PRMTs. In this work, we conducted chemical modifications on compound 6, resulting in a series of (2-(benzyloxy)phenyl)methanamine derivatives as potent inhibitors of CARM1. Among them, compound 17e displayed remarkable potency and selectivity for CARM1 (IC50 = 2 ± 1 nM), along with notable antiproliferative effects against melanoma cell lines. Cellular thermal shift assay and western blot experiments confirmed that compound 6 effectively targets CARM1 within cells. Furthermore, compound 17e displayed good antitumor efficacy in a melanoma xenograft model, indicating that this compound warrants further investigation as a potential anticancer agent.

Uncovering the Effect of A-Site Cations on Localized Excitons Photoluminescence of Manganese-Doped Zinc Chloride Nanocrystals.

Elucidating the key factors that affect the localized excitons (LEs) photoluminescence (PL) in lead-free metal halide nanocrystals (NCs) is important for their optoelectronic applications. However, the effect of A-site cations on LEs based PL is not well understood. Herein, we varied the A-site cation ratio (Rb/Cs) to investigate the influence on LEs based PL in manganese-doped zinc chloride NCs. Through time-resolved photoluminescence (TR-PL) spectra and density functional theory (DFT) calculations, we discovered that Cl vacancy is energetically more favorable in Mn2+-doped Rb3ZnCl5 NCs compared to Mn2+-doped Cs3ZnCl5 NCs. The higher concentration of Cl vacancy increases the nonradiative recombination process in Rb3ZnCl5:Mn2+ NCs, ultimately determining the PL efficiency. This research enhances the understanding of the A-site cation effect on LEs-based PL in lead-free metal halide NCs.

Simultaneous EEG-fMRI Investigation of Rhythm-Dependent Thalamo-Cortical Circuits Alteration in Schizophrenia.

Schizophrenia is accompanied by aberrant interactions of intrinsic brain networks. However, the modulatory effect of electroencephalography (EEG) rhythms on the functional connectivity (FC) in schizophrenia remains unclear. This study aims to provide new insight into network communication in schizophrenia by integrating FC and EEG rhythm information. After collecting simultaneous resting-state EEG-functional magnetic resonance imaging data, the effect of rhythm modulations on FC was explored using what we term "dynamic rhythm information." We also investigated the synergistic relationships among three networks under rhythm modulation conditions, where this relationship presents the coupling between two brain networks with other networks as the center by the rhythm modulation. This study found FC between the thalamus and cortical network regions was rhythm-specific. Further, the effects of the thalamus on the default mode network (DMN) and salience network (SN) were less similar under alpha rhythm modulation in schizophrenia patients than in controls ([Formula: see text]). However, the similarity between the effects of the central executive network (CEN) on the DMN and SN under gamma modulation was greater ([Formula: see text]), and the degree of coupling was negatively correlated with the duration of disease ([Formula: see text], [Formula: see text]). Moreover, schizophrenia patients exhibited less coupling with the thalamus as the center and greater coupling with the CEN as the center. These results indicate that modulations in dynamic rhythms might contribute to the disordered functional interactions seen in schizophrenia.

Develop a radiomics-based machine learning model to predict the stone-free rate post-percutaneous nephrolithotomy.

Radiomics and machine learning have been extensively utilized in the realm of urinary stones, particularly in forecasting stone treatment outcomes. The objective of this study was to integrate clinical variables and radiomic features to develop a machine learning model for predicting the stone-free rate (SFR) following percutaneous nephrolithotomy (PCNL). A total of 212 eligible patients who underwent PCNL surgery at the Second Affiliated Hospital of Nanchang University were included in a retrospective analysis. Preoperative clinical variables and non-contrast-enhanced CT images of all patients were collected, and radiomic features were extracted after delineating the stone ROI. Univariate analysis was conducted to identify clinical variables strongly correlated with the stone-free rate after PCNL, and the least absolute shrinkage and selection operator algorithm (lasso regression) was utilized to screen radiomic features. Four supervised machine learning algorithms, including Logistic Regression, Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Gradient Boosting Decision Tree (GBDT), were employed. The clinical variables with strong correlation and screened radiomic features were integrated into the four machine learning algorithms to construct a prediction model, and the receiver operating curve was plotted. The area under the receiver operating curve (AUC), the accuracy rate, the specificity, etc., were used to evaluate the predictive performance of the four models. After analyzing postoperative statistics, the stone-free rate following the procedure was found to be 70.3% (n = 149). Among the various clinical variables examined, factors, such as stone number, stone diameter, stone CT value, stone location, and history of stone surgery, were identified as statistically significant in relation to the stone-free rate after PCNL. A total of 121 radiomic features were extracted, and through lasso regression, 7 features most closely associated with the stone-free rate post-PCNL were identified. The predictive accuracy of different models (Logistic Regression, RF, XGBoost, and GBDT) for determining the stone-free rate after PCNL was evaluated, yielding accuracies of 78.1%, 76.6%, 75.0%, and 73.4%, respectively. The corresponding area under the curve AUC (95%CI) were 0.85 (0.83-0.89), 0.81 (0.76-0.85), 0.82 (0.78-0.85), and 0.77 (0.73-0.81), positioning these models among the top performers in logistic regression prediction. In terms of predictive importance scores, the key factors identified by the logistic regression model were number of stone, zone percentage, stone diameter, and surface area. Similarly, the RF model highlighted number of stone, stone CT value, stone diameter, and surface area as the top predictors. Among the four machine learning models, the logistic regression model demonstrated the highest accuracy and discrimination ability in predicting the stone-free rate following PCNL. In comparison to XGBoost and GBDT, RF also exhibited superior accuracy and a certain level of discrimination ability. However, based on the performance of all four models, logistic regression is more likely to aid in clinical decision-making by assisting clinicians in diagnosing PCNL in patients. This enables us to effectively predict the presence of residual stones post-surgery and ultimately select patients who are suitable candidates for PCNL.

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.

Epstein-Barr virus-driven metabolic alterations contribute to the viral lytic reactivation and tumor progression in nasopharyngeal carcinoma.

Metabolic reprogramming induced by Epstein-Barr virus (EBV) often mirrors metabolic changes observed in cancer cells. Accumulating evidence suggests that lytic reactivation is crucial in EBV-associated oncogenesis. The aim of this study was to explore the role of metabolite changes in EBV-associated malignancies and viral life cycle control. We first revealed that EBV (LMP1) accelerates the secretion of the oncometabolite D-2HG, and serum D-2HG level is a potential diagnostic biomarker for NPC. EBV (LMP1)-driven metabolite changes disrupts the homeostasis of global DNA methylation and demethylation, which have a significantly inhibitory effect on active DNA demethylation and 5hmC content. We found that loss of 5hmC indicates a poor prognosis for NPC patients, and that 5hmC modification is a restriction factor of EBV reactivation. We confirmed a novel EBV reactivation inhibitor, α-KG, which inhibits the expression of EBV lytic genes with CpG-containing ZREs and the latent-lytic switch by enhancing 5hmC modification. Our results demonstrate a novel mechanism of which metabolite abnormality driven by EBV controls the viral lytic reactivation through epigenetic modification. This study presents a potential strategy for blocking EBV reactivation, and provides potential targets for the diagnosis and therapy of NPC.

Artificial intelligence-assisted measurements of coronary computed tomography angiography parameters such as stenosis, flow reserve and fat attenuation for predicting major adverse cardiac events in patients with coronary arterial disease.

Advancements in artificial intelligence (AI) offer promising tools for improving diagnostic accuracy and patient outcomes in cardiovascular medicine. This study explores the potential of AI-assisted measurements in enhancing the prediction of major adverse cardiac events (MACE) in patients with coronary artery disease (CAD). We conducted a retrospective cohort study involving patients diagnosed with CAD who underwent coronary computed tomography angiography (CCTA). Participants were classified into MACE and non-MACE groups based on their clinical outcomes. Clinical characteristics and AI-assisted measurements of CCTA parameters, including CT-derived fractional flow reserve (CT-FFR) and fat attenuation index (FAI), were collected. Both univariate and multivariable logistic regression analyses were performed to identify independent predictors of MACE, which were used to build predictive models. Statistical analyses revealed three independent predictors of MACE: severe stenosis, CT-FFR ≤ 0.8, and mean FAI (P < 0.05). Seven predictive models incorporating various combinations of these predictors were developed. The model combining all three predictors demonstrated superior performance, as evidenced by the receiver operating characteristic (ROC) curve, with an area under the curve (AUC) of 0.811 (95% CI 0.774 - 0.847), a sensitivity of 0.776, and a specificity of 0.726. Our findings suggest that AI-assisted CCTA analysis, particularly using FFR and FAI, could significantly improve the prediction of MACE in CAD patients, thereby potentially aiding clinical decision-making.

Structural insights into the functional mechanism of the ubiquitin ligase E6AP.

E6AP dysfunction is associated with Angelman syndrome and Autism spectrum disorder. Additionally, the host E6AP is hijacked by the high-risk HPV E6 to aberrantly ubiquitinate the tumor suppressor p53, which is linked with development of multiple types of cancer, including most cervical cancers. Here we show that E6AP and the E6AP/E6 complex exist, respectively, as a monomer and a dimer of the E6AP/E6 protomer. The short α1-helix of E6AP transforms into a longer helical structure when in complex with E6. The extended α1-helices of the dimer intersect symmetrically and contribute to the dimerization. The two protomers sway around the crossed region of the two α1-helices to promote the attachment and detachment of substrates to the catalytic C-lobe of E6AP, thus facilitating ubiquitin transfer. These findings, complemented by mutagenesis analysis, suggest that the α1-helix, through conformational transformations, controls the transition between the inactive monomer and the active dimer of E6AP.

Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase.

Acute myeloid leukemia (AML) is a blood system malignancy where sirtuin 5 (SIRT5) is abnormally expressed in AML cell lines. This study aimed to investigate the SIRT5 effects on the viability and apoptosis of AML cell lines. The mRNA and protein expression levels of succinylation regulatory enzyme in clinical samples and AML cell lines were detected by real-time quantitative polymerase chain reaction and western blotting while cell viability was measured using cell counting kit-8 assay. The apoptosis rate was assessed with flow cytometry. The interaction between SIRT5 and glycine decarboxylase (GLDC) was determined by co-immunoprecipitation and immunofluorescence staining techniques. Results indicated higher mRNA and protein expression levels of SIRT5 in clinical AML samples of AML than in normal subjects. Similarly, cell viability was inhibited, and apoptosis was promoted by downregulating SIRT5, in addition to inhibition of SIRT5-mediated GLDC succinylation. Moreover, rescue experiment results showed that GLDC reversed the effects of SIRT5 knockdown on cell viability and apoptosis. These results, in combination with SIRT5 and GLDC interactions, suggested that SIRT5 was involved in mediating AML development through GLDC succinylation. SIRT5 inhibits GLDC succinylation to promote viability and inhibit apoptosis of AML cells, suggesting that SIRT5 encourages the development of AML.

Hypomethylation-associated LINC00987 downregulation induced lung adenocarcinoma progression by inhibiting the phosphorylation-mediated degradation of SND1.

DNA methylation, an epigenetic regulatory mechanism dictating gene transcription, plays a critical role in the occurrence and development of cancer. However, the molecular underpinnings of LINC00987 methylation in the regulation of lung adenocarcinoma (LUAD) remain elusive. This study investigated LINC00987 expression in LUAD patients through analysis of The Cancer Genome Atlas data sets. Quantitative real-time polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization assays were used to assess LINC00987 expression in LUAD. The bisulfite genomic sequence PCR (BSP) assay was used to determine the methylation levels of the LINC00987 promoter. The interaction between LINC00987 and SND1 was elucidated via immunoprecipitation and RNA pull-down assays. The functional significance of LINC00987 and SND1 in Calu-3 and NCI-H1688 cells was evaluated in vitro through CCK-8, EdU, Transwell, flow cytometry, and vasculogenic mimicry (VM) tube formation assays. LINC00987 expression decreased in LUAD concomitant with hypermethylation of the promoter region, while hypomethylation of the LINC00987 promoter in LUAD tissues correlated with tumor progression. Treatment with 5-Aza-CdR augmented LINC00987 expression and inhibited tumor growth. Mechanistically, LINC00987 overexpression impeded LUAD progression and VM through direct binding with SND1, thereby facilitating its phosphorylation and subsequent degradation. Additionally, overexpression of SND1 counteracted the adverse effects of LINC00987 downregulation on cell proliferation, apoptosis, cell migration, invasion, and VM in LUAD in vitro. In conclusion, this pioneering study focuses on the expression and function of LINC00987 and reveals that hypermethylation of the LINC00987 gene may contribute to LUAD progression. LINC00987 has emerged as a potential tumor suppressor gene in tumorigenesis through its binding with SND1 to facilitate its phosphorylation and subsequent degradation.

Analysis of the thickness characteristics of the left atrial posterior wall and its correlation with the low and no voltage areas of the left atrial posterior wall in patients with atrial fibrillation.

OBJECTIVE: To analyze the relationship between the thickness of the left atrial posterior wall and the low and no voltage zones in the left atrial posterior wall in patients with atrial fibrillation (AF). METHODS: 61 patients admitted to our cardiology department for AF and radiofrequency ablation of AF from January 1, 2020 to May 30, 2022 were enrolled according to inclusion and exclusion criteria. The atrial wall thickness was measured by CT scan. Baseline data, preoperative cardiac ultrasound data, preoperative biochemical parameters, low voltage zone (fibrotic zone) and no voltage zone (scar zone) in the left atrial posterior wall area, and various parameters of posterior left atrial wall thickness were collected. RESULTS: The differences of the thickness between the upper, middle and lower mean levels of the left atrial posterior wall were statistically significant (P = 0.004). The results showed that body mass index was weakly positively correlated with the mean level of total left atrial posterior wall thickness (r = 0.426, P = 0.001) and was statistically significant. The remaining indices were positively or negatively correlated with the mean level of total left atrial posterior wall thickness, but none were statistically significant (P > 0.05). CONCLUSIONS: Both left atrial posterior wall low-voltage zone and voltage-free zone were positively correlated with the mean total left atrial posterior wall thickness, and left atrial posterior wall low-voltage zone and voltage-free zone were significantly positively correlated. Body mass index was weakly positively correlated with total left atrial posterior wall thickness.

Discovery of Urea Derivatives of Celastrol as Selective Peroxiredoxin 1 Inhibitors against Colorectal Cancer Cells.

Peroxiredoxin (PRDX1) is a tumor-overexpressed antioxidant enzyme for eliminating excessive reactive oxygen species (ROS) to protect tumor cells from oxidative damage. Herein, a series of celastrol urea derivatives were developed based on its cocrystal structure with PRDX1, with the aim of pursuing a PRDX1-specific inhibitor. Among them, derivative 15 displayed potent anti-PRDX1 activity (IC50 = 0.35 µM) and antiproliferative potency against colon cancer cells. It covalently bound to Cys-173 of PRDX1 (KD = 0.37 µM), which was secured by the cocrystal structure of PRDX1 with an analogue of 15 while exhibiting weak inhibitory effects on PRDX2-PRDX6 (IC50 > 50 µM), indicating excellent PRDX1 selectivity. Treatment with 15 dose-dependently decreased the mitochondria membrane potential of SW620 cells, probably due to ROS induced by PRDX1 inhibition, leading to cell apoptosis. In colorectal cancer cell xenograft model, it displayed potent antitumor efficacy with superior safety to celastrol. Collectively, 15 represents a promising PRDX1 selective inhibitor for the development of anticolorectal cancer agents.

Transition Metal (Co, V, W, Zr) Single-Atom Decorated Biphenylene for Enhancing the Sensing Performance of SF6 Decomposition Molecules.

The highly sensitive gas sensors used to monitor the decomposition of toxic gases in the dielectric materials of electrical equipment are vital in preventing safety problems arising from corrosion of the equipment. Recently, biphenylene (BPN) has been prepared through surface interpolymer hydrofluorination (HF zipper) reaction, whereas potential gas-sensitive devices based on the BPN monolayer have lacked in-depth investigation. The stable geometries, adsorption energies, interlayer distances, and charge transfers of small molecules of toxic gases (H2S, SO2, SOF2, SO2F2) produced by SF6 chalcogenide molecules of decomposition adsorbed on the original BPN monolayer are systematically researched by using nonequilibrium Green's function methods and density functional theory. The results indicated that all small molecules adsorbed on the BPN monolayer are physisorbed, while the type of adsorption turned from physisorption to chemisorption when BPN carried out adsorption with adsorbing a transition metal atom (TMA). In addition, the characteristics of current-voltage (I-V) curves of H2S and SO2 based on the TMA-BPN gas sensors revealed that the currents in BPN-based gas sensors displayed an obvious anisotropy, and the currents in the zigzag direction are larger than that in the armchair orientation regardless of the molecular adsorption cases. Moreover, the difference of currents for TMA-decorated BPN sensors changed more remarkably before and after the adsorption of H2S and SO2 in the zigzag direction. This work offers insights into the design of gas-sensitive devices through the adsorption of small molecules on the TMA-decorated BPN monolayer.