Background: Elevated expression of SLC7A11, in conjunction with glucose deprivation, has revealed disulfidptosis as an emerging cell death modality. However, the prevalence of disulfidptosis across tumor cell lines, irrespective of SLC7A11 levels, remains uncertain. Additionally, deletion of the ribophorin I (RPN1) gene imparts resistance to disulfidptosis, yet the precise mechanism linking RPN1 to disulfidptosis remains elusive. The aim of this study is to determine the mechanism of RPN1-induced disulfidptosis and to determine the possibility of RPN1 as a pan-cancer marker. Methods: We hypothesized the widespread occurrence of disulfidptosis in various tumor cells, and proposed that RPN1-mediated disulfidptosis may be executed through cell skeleton breakdown. Experimental validation was conducted via flow cytometry, immunofluorescence, and western blot techniques. Furthermore, given RPN1's status as an emerging cell death marker, we utilized bioinformatics to analyze its expression in tumor tissues, clinical relevance, mechanisms within the tumor microenvironment, and potential for immunotherapy. Results: Conducting experiments on breast cancer (MDA-MB-231) and lung cancer (A549) cell lines under glucose-starved conditions, we found that RPN1 primarily induces cell skeleton breakdown to facilitate disulfidptosis. RPN1 demonstrated robust messenger RNA (mRNA) expression across 16 solid tumors, validated by data from 12 tumor types in the Gene Expression Omnibus (GEO). Across 12 cancer types, RPN1 exhibited significant diagnostic potential, particularly excelling in accuracy for glioblastoma (GBM). Elevated RPN1 expression in tumor tissues was found to correlate with improved overall survival (OS) in certain cancers [diffuse large B-cell lymphoma (DLBC) and thymoma (THYM)] but poorer prognosis in others [adrenocortical carcinoma (ACC), kidney chromophobe (KICH), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD)]. RPN1 is enriched in immune-related pathways and correlates with immune scores in tumor tissues. In urothelial carcinoma (UCC), RPN1 demonstrates potential in predicting the efficacy of anti-programmed cell death ligand 1 (PD-L1) immune therapy. Conclusions: This study underscores RPN1's role in facilitating disulfidptosis, its broad relevance as a pan-cancer biomarker, and its association with the efficacy of anti-PD-L1 immune therapy.
Three new indole alkaloids, named talatensindoids A-C (1-3), together with two known biogenetically related indole alkaloids tryptamine (4) and L-tryptophan (5) were isolated from the Talaromyces assiutensis JTY2 based on the guidance of OSMAC approach. The structures of these indole alkaloids were determined by comprehensive spectroscopic analyses. The absolute configuration of 3 was confirmed by X-ray crystallographic analysis. Compound 1 represent the rare example of a chlorine-substituted indole alkaloid from natural products. The inhibitory activity of compounds 1-5 against two phytopathogenic fungi and three phytopathogenic bacteria was evaluated. Compound 1 exhibited broad spectrum antibacterial activities.
Background: The neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level are inflammatory markers related to tumor growth and metabolism. This study investigated the value of preoperative NLR, LDH and the combination of NLR and LDH (NLR-LDH) for predicting colorectal cancer liver metastasis (CRLM) and tumor prognosis in the early stages of colorectal cancer (CRC). Materials and methods: Three hundred patients undergoing CRC resection were included. Logistic regression analysis was used to estimate the correlation between CRLM time and inflammatory markers, and Kaplan-Meier survival and Cox regression analyses were used to estimate overall survival (OS). Forest plots were prepared based on the multivariate Cox analysis model and evaluated by receiver operating characteristic (ROC) curve analysis. Results: The NLR cut-off value was 2.071 according to the ROC curve. The multivariate analysis showed that the elevated LDH level and a high NLR-LDH level were independent predictors of synchronous CRLM and OS (p < 0.05). The combination of a high NLR and elevated LDH and NLR-LDH levels suggested a poor prognosis and a significantly shorter median survival time than a low NLR and low levels of LDH and NLR-LDH. The ROC curve analysis results illustrated that the predictive value of the NLR-LDH score for synchronous CRLM [area under the curve (AUC) = 0.623, p < 0.001] and OS (AUC = 0.614, p = 0.001) was superior to that of the NLR or LDH score used alone. Conclusion: LDH and NLR-LDH are reliable, easy-to-use, independent biomarkers for predicting synchronous or metachronous CRLM and OS in CRC patients. The NLR is an important monitoring index for CRLM. Preoperative NLR, LDH and NLR-LDH may help to guide the use of therapeutic strategies and cancer surveillance.
BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2, and outbreaks have occurred worldwide. Laboratory test results are an important basis for clinicians to determine patient condition and formulate treatment plans. METHODS: Fifty-two thousand six hundred forty-four laboratory test results with continuous values of adult inpatients who were diagnosed with COVID-19 and hospitalized in the Fifth Hospital in Wuhan between 16 January 2020 and 18 March 2020 were compiled. The first and last test results were compared between survivors and non-survivors with variance test or Welch test. Laboratory test variables with significant differences were then included in the temporal change analysis. RESULTS: Among 94 laboratory test variables in 82 survivors and 25 non-survivors with COVID-19, white blood cell count, neutrophil count/percentage, mean platelet volume, platelet distribution width, platelet-large cell percentage, hypersensitive C-reactive protein, procalcitonin, D-dimer, fibrin (ogen) degradation product, middle fluorescent reticulocyte percentage, immature reticulocyte fraction, lactate dehydrogenase were significantly increased (P < 0.05), and lymphocyte count/percentage, monocyte percentage, eosinophil percentage, prothrombin activity, low fluorescent reticulocyte percentage, plasma carbon dioxide, total calcium, prealbumin, total protein, albumin, albumin-globulin ratio, cholinesterase, total cholesterol, nonhigh-density/low-density/small-dense-low-density lipoprotein cholesterol were significantly decreased in non-survivors compared with survivors (P < 0.05), in both first and last tests. Prothrombin time, prothrombin international normalized ratio, nucleated red blood cell count/percentage, high fluorescent reticulocyte percentage, plasma uric acid, plasma urea nitrogen, cystatin C, sodium, phosphorus, magnesium, myoglobin, creatine kinase (isoenzymes), aspartate aminotransferase, alkaline phosphatase, glucose, triglyceride were significantly increased (P < 0.05), and eosinophil count, basophil percentage, platelet count, thrombocytocrit, antithrombin III, red blood cell count, haemoglobin, haematocrit, total carbon dioxide, acidity-basicity, actual bicarbonate radical, base excess in the extracellular fluid compartment, estimated glomerular filtration rate, high-density lipoprotein cholesterol, apolipoprotein A1/ B were significantly decreased in non-survivors compared with survivors (P < 0.05), only in the last tests. Temporal changes in 26 variables, such as lymphocyte count/percentage, neutrophil count/percentage, and platelet count, were obviously different between survivors and non-survivors. CONCLUSIONS: By the comprehensive usage of the laboratory markers with different temporal changes, patients with a high risk of COVID-19-associated death or progression from mild to severe disease might be identified, allowing for timely targeted treatment.
Biomarkers/blood , COVID-19/blood , Survivors/statistics & numerical data , C-Reactive Protein/metabolism , Female , Fibrin Fibrinogen Degradation Products/metabolism , Humans , Inpatients/statistics & numerical data , Leukocyte Count , Lymphocyte Count , Male , Middle Aged , Neutrophils , Pandemics , Procalcitonin/blood , Retrospective Studies , SARS-CoV-2 , Time Factors
Modulation transfer function (MTF) is an important figure of image resolution of microchannel plate image intensifiers (MCPIIs). Dynamic MTFs of two Gen-II MCPIIs were measured under pulsed voltage operation (gated mode) using a narrow slit. The resolution determined by the MTF was calculated under various bias voltages and gate widths. Our numerical results show that with the increase of the reverse bias of MCPIIs, the resolution is improved rapidly below 40 V and then gradually decreased. With the MCP bias increased, both MCPIIs start to suffer rapid reductions in resolution at 800 and 750 V, respectively. The change of phosphor voltage has little influence on the resolution. The resolution declines rapidly with the decrease of the gate width below 20 ns but goes steady above 30 ns. We explored causes of these variations.
