Cuproptosis in ccRCC: key player in therapeutic and prognostic targets

BackgroundClassical biomarkers have been used to classify clear cell renal cell carcinoma (ccRCC) patients in a variety of ways, and emerging evidences have indicated that cuproptosis is closely related to mitochondrial metabolism, thereby accelerating the development and progression of ccRCC. Nevertheless, the specific relationship between cuproptosis and the prognosis and treatment of ccRCC remains unclear.MethodsWe comprehensively integrated several ccRCC patient datasets into a large cohort. Following that, we systematically analyzed multi-omics data to demonstrate the differences between two cuproptosis clusters.ResultsWe identified two cuproptosis clusters in ccRCC patients. Among the two clusters, cluster 1 patients showed favorable prognosis. We then confirmed the significant differences between the two clusters, including more typical cancer hallmarks were enriched in cluster 2 patients; cluster 2 patients were more susceptible to develop mutations and had a lower level of gistic score and mRNAsi. Importantly, both Tumor Immune Dysfunction and Exclusion analysis and subclass mapping algorithm showed that cuproptosis 1 patients were more susceptible to be responded to immunotherapy. In addition, a prognostic signature was successfully developed and also showed prominent predictive power in response to immunotherapy.ConclusionAs a result of our findings, we were able to classify ccRCC patients according to cuproptosis in a novel way. By constructing the cuproptosis clusters and developing the signature, patients with ccRCC could have a more accurate prognosis prediction and better immunotherapy options

Nomograms predict prognosis and hospitalization time using non-contrast CT and CT perfusion in patients with ischemic stroke

BackgroundStroke is a major disease with high morbidity and mortality worldwide. Currently, there is no quantitative method to evaluate the short-term prognosis and length of hospitalization of patients.PurposeWe aimed to develop nomograms as prognosis predictors based on imaging characteristics from non-contrast computed tomography (NCCT) and CT perfusion (CTP) and clinical characteristics for predicting activity of daily living (ADL) and hospitalization time of patients with ischemic stroke.Materials and methodsA total of 476 patients were enrolled in the study and divided into the training set (n = 381) and testing set (n = 95). Each of them owned NCCT and CTP images. We propose to extract imaging features representing as the Alberta stroke program early CT score (ASPECTS) values from NCCT, ischemic lesion volumes from CBF, and TMAX maps from CTP. Based on imaging features and clinical characteristics, we addressed two main issues: (1) predicting prognosis according to the Barthel index (BI)–binary logistic regression analysis was employed for feature selection, and the resulting nomogram was assessed in terms of discrimination capability, calibration, and clinical utility and (2) predicting the hospitalization time of patients–the Cox proportional hazard model was used for this purpose. After feature selection, another specific nomogram was established with calibration curves and time-dependent ROC curves for evaluation.ResultsIn the task of predicting binary prognosis outcome, a nomogram was constructed with the area under the curve (AUC) value of 0.883 (95% CI: 0.781–0.985), the accuracy of 0.853, and F1-scores of 0.909 in the testing set. We further tried to predict discharge BI into four classes. Similar performance was achieved as an AUC of 0.890 in the testing set. In the task of predicting hospitalization time, the Cox proportional hazard model was used. The concordance index of the model was 0.700 (SE = 0.019), and AUCs for predicting discharge at a specific week were higher than 0.80, which demonstrated the superior performance of the model.ConclusionThe novel non-invasive NCCT- and CTP-based nomograms could predict short-term ADL and hospitalization time of patients with ischemic stroke, thus allowing a personalized clinical outcome prediction and showing great potential in improving clinical efficiency.SummaryCombining NCCT- and CTP-based nomograms could accurately predict short-term outcomes of patients with ischemic stroke, including whose discharge BI and the length of hospital stay.Key ResultsUsing a large dataset of 1,310 patients, we show a novel nomogram with a good performance in predicting discharge BI class of patients (AUCs > 0.850). The second nomogram owns an excellent ability to predict the length of hospital stay (AUCs > 0.800)

Characterization of the complete mitochondrial genome of the paddy frog Fejervarya multistriata (Anura: Dicroglossidae) and its phylogeny

The mitochondrial genome has proven to be a highly successful resource for the investigation of evolution and population genetics. Here, we present the complete mitochondrial genome of Fejervarya multistriata. The circle genome was found to be 17,759 bp in length, containing 13 protein-coding genes, 23 transfer RNA genes, 2 ribosomal RNA genes, and 1 noncoding control region that are conserved in most Dicroglossidae mitogenomes. The total base composition of the F. multistriata mitogenome is 28.04% A, 29.82% T, 26.99% C, and 15.15% G, which is typical for Amphibious animals’ mitochondrial genomes. Eight tRNAs are encoded on the light strand (tRNA-Gln, tRNA-Ala, tRNA-Asn, tRNA-Cys, tRNA-Tyr, tRNA-Ser, tRNA-Glu and tRNA-Pro). Only one PCG is encoded on the light strand (ND6), whereas the other genes are located on the heavy strand. Phylogenetic analyses were performed on the concatenated dataset of 13 PCGs at nucleotide levels with maximum likelihood (ML) and Bayesian analysis (BI) methods. The results showed that F. multistriata and F. limnocharis integrated into a big branch and they have a close genetic relationship. This study could provide important molecular data for species identification and the phylogenetic relationship of Fejervarya and related species

Research on Curriculum Design of 'Real-time Analysis and Design' Based on Multi-core Platform

The change of microprocessor to "multi-core" is not only a new start of the healthy progress of the processor technology, but also a milestone of the development history of computer technology. Naturally, curriculums which are closely related to the hardware will be adjusted with the appearance of "multi-core". In this paper, we introduced the practice and experience of curriculums design based on multi-core platform in the postgraduate and senior undergraduate course-"Real-time system analyses and design"

Dynamic simulation study of the secondary frequency regulation of a 1000 MW thermal power unit assisted by flywheel energy storage

The rapid development of new energy sources has brought a certain impact on the original power grid structure, accelerated the wear of unit equipment, and affected the stability, safety, and economy of thermal power unit operation, so it is proposed to add an energy storage system to solve the above problems. To analyze the secondary frequency regulation effect of thermal power units assisted by a flywheel energy storage system, a mathematical model of the control strategy on both sides of the boiler, steam turbine, and flywheel permanent magnet synchronous motor is proposed, and a two-regional power grid model is built through MATLAB/Simulink to simulate the frequency regulation effect of units with or without energy storage participation through step disturbance and continuous disturbance, which are 0.045 and 0.023 p.u. MW. Under step disturbance, the frequency fluctuation of the coupled energy storage system changed by 0.025 228 p.u. Hz, the time for the system to return to a steady state was shortened by 5.85 s, the maximum change of the frequency of the system in Region 2 was reduced by 0.025 579 p.u. Hz, and under continuous disturbance, the fluctuation of the output power of the steam turbine in Region 1 was reduced by 0.022 982 p.u. MW. In summary, under the same disturbance conditions in the outside world, the use of flywheel energy storage to assist the frequency regulation of thermal power units can effectively reduce the frequency fluctuation of the system, reduce the fluctuation of the output power of the steam turbine, reduce the loss of mechanical equipment, and extend the service life of the unit to a certain extent

Additional file 1 of Insights into the combined toxic impacts of phoxim and deltamethrin on the embryo-larval stage of zebrafish (Danio rerio)

Additional file 1: Table S1 Detailed information about the biochemical parameters tested. Table S2 Gene primer sequences in real time quantitative PCR reaction

Pathophysiological and behavioral deficits in developing mice following rotational acceleration-deceleration traumatic brain injury

Abusive head trauma (AHT) is the leading cause of death from trauma in infants and young children. An AHT animal model was developed on 12-day-old mice subjected to 90° head extension-flexion sagittal shaking repeated 30, 60, 80 and 100 times. The mortality and time until return of consciousness were dependent on the number of repeats and severity of the injury. Following 60 episodes of repeated head shakings, the pups demonstrated apnea and/or bradycardia immediately after injury. Acute oxygen desaturation was observed by pulse oximetry during respiratory and cardiac suppression. The cerebral blood perfusion was assessed by laser speckle contrast analysis (LASCA) using a PeriCam PSI system. There was a severe reduction in cerebral blood perfusion immediately after the trauma that did not significantly improve within 24 h. The injured mice began to experience reversible sensorimotor function at 9 days postinjury (dpi), which had completely recovered at 28 dpi. However, cognitive deficits and anxiety-like behavior remained. Subdural/subarachnoid hemorrhage, damage to the brain-blood barrier and parenchymal edema were found in all pups subjected to 60 insults. Proinflammatory response and reactive gliosis were upregulated at 3 dpi. Degenerated neurons were found in the cerebral cortex and olfactory tubercles at 30 dpi. This mouse model of repetitive brain injury by rotational head acceleration-deceleration partially mimics the major pathophysiological and behavioral events that occur in children with AHT. The resultant hypoxia/ischemia suggests a potential mechanism underlying the secondary rotational acceleration-deceleration-induced brain injury in developing mice