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BackgroundThe incidence of delirium in critically ill psychiatric patients is high， and there are many factors affecting delirium occurrence. At present， epidemiological studies on delirium among critically ill patients in psychiatric hospitals are limited.ObjectiveTo explore the risk factors for delirium in critically ill patients in a psychiatric hospital， so as to guide the clinical management of delirium in psychiatric hospitals.MethodsThis retrospective study included 427 critically ill patients who were admitted to Shenzhen Kangning Hospital from January 1， 2019 to May 31， 2021. The delirium situation， gender， age， pre-admission course of illness （duration from the onset of acute mental state changes to in-patient registration at a psychiatric hospital）， history of mental illness， history of cognitive dysfunction， history of using psychoactive substances， history of using sedative and hypnotic drugs， number of combined chronic diseases， number of combined drugs and type of disease were examined as potential risk factors for delirium. Single Logistic regression was used to analyze the potential risk factors for delirium， and the potential risk factors were incorporated into the multi-factor Logistic regression analysis model so as to gradually screen out the risk factors for delirium in critically ill psychiatric patients.ResultsDelirium was present in 33.49% （143/427） of critically ill patients. Multi-factor Logistic regression analysis demonstrated that the presence of delirium was associated with mental and behavioral disorders caused by psychoactive substances （OR=8.949， P

Diamond, a wide bandgap semiconductor material, has excellent physicochemical properties. It has great potential for application in high temperature, high frequency, high power electronic devices and other high technology fields. In order to study the electronic properties of diamond more precisely, an AM-response surface model is developed in this paper to investigate the electronic structures of diamond, P-doped diamond and N-doped diamond surfaces in depth. It is shown that there are three forms of charge states in the single vacancy on the diamond surface. When E=0 V, the negative charge energy level is -0.5 mV, the positive charge is 1 mV, and the zero level remains 0. And its energy level is unstable. In contrast, the double vacancy charge on the diamond surface varies depending on the valence band taken by E, and only one charge state exists. When E0, it is positive charge energy level. The electronic properties of the P-doped diamond semiconductor material are calculated to have a constant positive charge (1 mV). The electronic property of N-doped diamond semiconductor material is constant negative charge (-1mV).

ObjectiveTo picture the trajectory of changes in glucose and lipid metabolism among schizophrenic patients in long-term hospitalization.MethodsA total of 109 inpatients of Shenzhen Kangning Hospital from 2014 to 2022， who were diagnosed with schizophrenia based on the International Classification of Diseases， tenth edition （ICD-10） criteria， were recruited as subjects. Real-world follow-up data on longitudinal glucose metabolism （fasting blood glucose， glycosylated hemoglobin， C-peptide） and lipid metabolism （triglycerides， low density lipoprotein， high density lipoprotein， total cholesterol） were observed. The frequency of visit was once a year， with a total of 9 visits over 8 years.ResultsIn terms of glucose metabolism parameters， fasting blood glucose level decreased to 4.87 mmol/L at the 7th visit， lower than the baseline level （P

The small GTPase KRAS is localized at the plasma membrane where it functions as a molecular switch, coupling extracellular growth factor stimulation to intracellular signaling networks. In this process, KRAS recruits effectors, such as RAF kinase, to the plasma membrane where they are activated by a series of complex molecular steps. Defining the membrane-bound state of KRAS is fundamental to understanding the activation of RAF kinase and in evaluating novel therapeutic opportunities for the inhibition of oncogenic KRAS-mediated signaling. We combined multiple biophysical measurements and computational methodologies to generate a consensus model for authentically processed, membrane-anchored KRAS. In contrast to the two membrane-proximal conformations previously reported, we identify a third significantly populated state using a combination of neutron reflectivity, fast photochemical oxidation of proteins (FPOP), and NMR. In this highly populated state, which we refer to as "membrane-distal" and estimate to comprise ∼90% of the ensemble, the G-domain does not directly contact the membrane but is tethered via its C-terminal hypervariable region and carboxymethylated farnesyl moiety, as shown by FPOP. Subsequent interaction of the RAF1 RAS binding domain with KRAS does not significantly change G-domain configurations on the membrane but affects their relative populations. Overall, our results are consistent with a directional fly-casting mechanism for KRAS, in which the membrane-distal state of the G-domain can effectively recruit RAF kinase from the cytoplasm for activation at the membrane.

Introduction: Selenium is an essential micronutrient the human body requires, which is closely linked to health. Rice, a primary staple food globally, is a major source of human selenium intake. To develop selenium-enriched rice varieties, it is imperative to understand the mechanisms behind selenium's absorption and transport within rice, alongside identifying the key genes involved in selenium uptake, transport, and transformation within the plant. Methods: This study conducted transcriptome sequencing on four types of rice materials (two with low-selenium and two with high-selenium contents) across roots, stems, leaves, and panicles to analyze the gene expression differences. Results and discussion: Differential gene expression was observed in the various tissues, identifying 5,815, 6,169, 7,609, and 10,223 distinct genes in roots, stems, leaves, and panicles, respectively. To delve into these differentially expressed genes and identify the hub genes linked to selenium contents, weighted gene co-expression network analysis (WGCNA) was performed. Ultimately, 10, 8, 7, and 6 hub genes in the roots, stems, leaves, and panicles, respectively, were identified. The identification of these hub genes substantially aids in advancing our understanding of the molecular mechanisms involved in selenium absorption and transport during the growth of rice. [ABSTRACT FROM AUTHOR]

The most widely used cancer animal model is the human-murine tumor xenograft. Unbiased molecular dissection of tumor parenchyma versus stroma in human-murine xenografts is critical for elucidating dysregulated protein networks/pathways and developing therapeutics that may target these two functionally codependent compartments. Although antibody-reliant technologies (e.g., immunohistochemistry, imaging mass cytometry) are capable of distinguishing tumor-proper versus stromal proteins, the breadth or extent of targets is limited. Here, we report an antibody-free targeted cross-species glycoproteomic (TCSG) approach that enables direct dissection of human tumor parenchyma from murine tumor stroma at the molecular/protein level in tumor xenografts at a selectivity rate presently unattainable by other means. This approach was used to segment/dissect and obtain the protein complement phenotype of the tumor stroma and parenchyma of the metastatic human lung adenocarcinoma A549 xenograft, with no need for tissue microdissection prior to mass-spectrometry analysis. An extensive molecular map of the tumor proper and the associated microenvironment was generated along with the top functional N-glycosylated protein networks enriched in each compartment. Importantly, immunohistochemistry-based cross-validation of selected parenchymal and stromal targets applied on human tissue samples of lung adenocarcinoma and normal adjacent tissue is indicative of a noteworthy translational capacity for this unique approach that may facilitate identifications of novel targets for next generation antibody therapies and development of real time preclinical tumor models.

Oncogenic Ras mutants play a major role in the etiology of most aggressive and deadly carcinomas in humans. In spite of continuous efforts, effective pharmacological treatments targeting oncogenic Ras isoforms have not been developed. Cell-surface proteins represent top therapeutic targets primarily due to their accessibility and susceptibility to different modes of cancer therapy. To expand the treatment options of cancers driven by oncogenic Ras, new targets need to be identified and characterized at the surface of cancer cells expressing oncogenic Ras mutants. Here, we describe a mass spectrometry-based method for molecular profiling of the cell surface using KRasG12V transfected MCF10A (MCF10A-KRasG12V) as a model cell line of constitutively activated KRas and native MCF10A cells transduced with an empty vector (EV) as control. An extensive molecular map of the KRas surface was achieved by applying, in parallel, targeted hydrazide-based cell-surface capturing technology and global shotgun membrane proteomics to identify the proteins on the KRasG12V surface. This method allowed for integrated proteomic analysis that identified more than 500 cell-surface proteins found unique or upregulated on the surface of MCF10A-KRasG12V cells. Multistep bioinformatic processing was employed to elucidate and prioritize targets for cross-validation. Scanning electron microscopy and phenotypic cancer cell assays revealed changes at the cell surface consistent with malignant epithelial-to-mesenchymal transformation secondary to KRasG12V activation. Taken together, this dataset significantly expands the map of the KRasG12V surface and uncovers potential targets involved primarily in cell motility, cellular protrusion formation, and metastasis.

Oncogenic Ras mutants play a major role in the etiology of most aggressive and deadly carcinomas in humans. In spite of continuous efforts, effective pharmacological treatments targeting oncogenic Ras isoforms have not been developed. Cell-surface proteins represent top therapeutic targets primarily due to their accessibility and susceptibility to different modes of cancer therapy. To expand the treatment options of cancers driven by oncogenic Ras, new targets need to be identified and characterized at the surface of cancer cells expressing oncogenic Ras mutants. Here, we describe a mass spectrometry-based method for molecular profiling of the cell surface using KRasG12V transfected MCF10A (MCF10A-KRasG12V) as a model cell line of constitutively activated KRas and native MCF10A cells transduced with an empty vector (EV) as control. An extensive molecular map of the KRas surface was achieved by applying, in parallel, targeted hydrazide-based cell-surface capturing technology and global shotgun membrane proteomics to identify the proteins on the KRasG12V surface. This method allowed for integrated proteomic analysis that identified more than 500 cell-surface proteins found unique or upregulated on the surface of MCF10A-KRasG12V cells. Multistep bioinformatic processing was employed to elucidate and prioritize targets for cross-validation. Scanning electron microscopy and phenotypic cancer cell assays revealed changes at the cell surface consistent with malignant epithelial-to-mesenchymal transformation secondary to KRasG12V activation. Taken together, this dataset significantly expands the map of the KRasG12V surface and uncovers potential targets involved primarily in cell motility, cellular protrusion formation, and metastasis.

Objective: To screen ferroptosis genes related to prognosis of malignant pleural mesothelioma (MPM), explore the relationship between ferroptosis and tumor immune microenvironment and provide a new perspective for targeting and immunotherapy of MPM patients. Methods: The differentially expressed genes (DEGs) in MPM tumor group and normal group were analyzed in GEO database; intersection of DEGs and ferroptosis genes to obtain differentially expressed ferroptosis-related genes (DE-FRGs). GO, KEGG function enrichment and protein protein interaction (PPI) were used to identify the signal pathways mainly involved by DEFRGs. The prognosis related ferroptosis genes were identified by univariate COX analysis. LASSO regression analysis was used to screen the best DE-FRGs for establishing the risk prediction model, and a risk prognosis model based on the best DE-FRGs was established by multivariate cox analysis to verify the prediction effect of the model. Finally, CIBERSORT and other algorithms were used to analyze tumor immune cell infiltration and evaluate immune microenvironment. Results: Twenty-four prognosis related DE-FRGs were screened, which were mainly concentrated in ferroptosis, transcriptional regulation and response to inorganic substances. A MPM risk prediction model based on five ferroptosis-related genes (ALDH3A2, CAV1, HRAS, CDCA3 and RRM2) was established and validated. In the model, the proportion of CD8+T cells and macrophages in high-risk group were higher, while the proportion of B lymphocytes was lower. In addition, PD-1, CTLA-4 and their ligands at immune checkpoint had higher expression status in high-risk group. Conclusion: The MPM risk prediction model based on five ferroptosis-related genes is established, and the immune status in the model is clarified. It provides a certain research basis for targeting and immunotherapy of MPM. The predictive ability of this model in MPM needs to be further verified in clinical practice to better predict disease stratification and treatment management. [ABSTRACT FROM AUTHOR]

Zero-valent iron permeable reactive barrier (ZVI-PRB) has attracted great attention for its high efficiency and low cost in the in-site remediation process. However, passivating oxide layers are usually yielded and covered on the surface of ZVI, which shorten the service life of PRB. In this study, Morganella morganii subsp was used to hydrolyse the passivating oxide layers on ZVI. The hydrolysing condition was optimized. The highest Cr(VI) removal efficiency was achieved with glucose of 4 g/L, yeast powder of 6 g/L and pH = 7. With Morganella morganii subsp, the maximum removal quality of ZVI was increased from 19.96 mg/g to 24.35 mg/g, indicating Morganella morganii subsp could improve the reduction ability of ZVI. SEM-EDS analysis also showed that M. morganii subsp could promote the surface corrosion of ZVI and adsorb Cr simultaneously.