Precipitation nowcasting is extremely important in disaster prevention and mitigation, and can improve the quality of meteorological forecasts. In recent years, deep learning-based spatiotemporal ...sequence prediction models have been widely used in precipitation nowcasting, obtaining better prediction results than numerical weather prediction models and traditional radar echo extrapolation results. Because existing deep learning models rarely consider the inherent interactions between the model input data and the previous output, model prediction results do not sufficiently meet the actual forecast requirement. We propose a Modified Convolutional Gated Recurrent Unit (M-ConvGRU) model that performs convolution operations on the input data and previous output of a GRU network. Moreover, this adopts an encoder–forecaster structure to better capture the characteristics of spatiotemporal correlation in radar echo maps. The results of multiple experiments demonstrate the effectiveness of the proposed model. The balanced mean absolute error (B-MAE) and balanced mean squared error (B-MSE) of M-ConvGRU are slightly lower than Convolutional Long Short-Term Memory (ConvLSTM), but the mean absolute error (MAE) and mean squared error (MSE) of M-ConvGRU are 6.29% and 10.25% lower than ConvLSTM, and the prediction accuracy and prediction performance for strong echo regions were also improved.
Abstract
Purpose
The combination of Xiaozheng decoction with postoperative intravesical instillation has been shown to improve the prognosis of bladder cancer patients and prevent recurrence. ...However, the mechanisms underlying the efficacy of this herbal formula remain largely unclear. This research aims to identify the important components of Xiaozheng decoction and explore their anti-bladder cancer effect and mechanism using network pharmacology-based experiments.
Methods
The chemical ingredients of each herb in the Xiaozheng decoction were collected from the Traditional Chinese Medicine (TCM) database. Network pharmacology was employed to predict the target proteins and pathways of action. Disease databases were utilized to identify target genes associated with bladder cancer. A Protein–Protein Interaction (PPI) network was constructed to illustrate the interaction with intersected target proteins. Key targets were identified using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. A compound-target-pathway network was established after molecular docking predictions. In vitro experiments with bladder cancer cell lines were conducted using core chemical components confirmed by ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-qTOF-MS) to verify the conclusions of network pharmacology.
Results
45 active compounds were extracted, and their relationships with Traditional Chinese Medicines (TCMs) and protein targets were presented, comprising 7 herbs, 45 active compounds, and 557 protein targets. The intersection between potential TCM target genes and bladder cancer-related genes yielded 322 genes. GO and KEGG analyses indicated that these targets may be involved in numerous cancer-related pathways. Molecular docking results showed that candidate compounds except mandenol could form stable conformations with the receptor. In vitro experiments on three bladder cancer cell lines demonstrated that quercetin and two other impressive new compounds, bisdemethoxycurcumin (BDMC) and kumatakenin, significantly promoted cancer cell apoptosis through the B-cell lymphoma 2/Bcl-2-associated X (Bcl-2/BAX) pathway and inhibited proliferation and migration through the glycogen synthase kinase 3 beta (GSK3β)/β-catenin pathway.
Conclusion
By employing network pharmacology and conducting in vitro experiments, the mechanism of Xiaozheng decoction’s effect against bladder cancer was tentatively elucidated, and its main active ingredients and targets were identified, providing a scientific basis for future research.
Bladder cancer (BC) belongs to one of the most common and highly heterogeneous malignancies. Ferroptosis is a newly discovered regulated cell death (RCD), characterized by accumulation of toxic lipid ...peroxides, and plays a crucial role in tumor progression. Here, we conducted a comprehensive analysis on the transcriptomics data of ferroptosis-related genes in BC based on The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets. In our study, a 6-gene signature was identified based on the potential prognostic ferroptotic regulatory genes. Furthermore, our signature revealed a good independent prognostic ability in BC. Patients with low-risk score exhibited higher FGFR3 mutation rates while high risk score had a positive association with higher RB1 mutation rates. Meanwhile, higher proportions of macrophages were observed in high BC risk group simultaneously with four methods. Unexpectedly, the risk score showed a significant positive correlation with epithelial-mesenchymal transition (EMT) status. Functional assays indicated that CRYAB and SQLE knockdown was associated with attenuated invasion capacity. Our study revealed a ferroptosis-related risk model for predicting prognostic and BC progression. Our results indicate that targeting ferroptosis may be a therapeutic strategy for BC.
China has undergone rapid urbanization over the past few decades, and accordingly, changes have occurred in the extreme precipitation events. However, few studies have focused on the relationships ...between rapid urbanization and extreme precipitation events in southwest China, particularly in the Sichuan–Chongqing area, which has a complex topography and has experienced rapid urbanization over the past few decades. This is the first study to analyze the impact of urbanization on the amount, frequency, and intensity of extreme summer (June–August) precipitation events over the past 30 years. Our results indicate that extreme precipitation events primarily occurred in the urban-dominated Sichuan basin, particularly during the fast urbanization development stage (FUDS) of 1994–2015. Extreme precipitation amounts and intensities increased during the FUDS, implying the greater probability of individual precipitation events developing into heavy or extreme events in a particular area. In addition, the probability distribution functions of the occurrence and volume of strong convective events significantly increased during the FUDS. Finally, the annual increase in urban-scale land surface air temperature, increase in wet convection, and changes in wind speed are identified as essential factors leading to extreme precipitation events in this region.
Objective: To observe the effects of Grifola frondosa polysaccharides (GFP) on proliferation, apoptosis, cell cycle, expression of cyclin and apoptotic proteins of hepatocellular carcinoma HepG2 ...cells of human, and to explore the mechanism of its inhibition on proliferation of HepG2 cells. Methods: The experiment was divided into PGF/control group. Different concentrations of PGF solution were used to interfere with human hepatocellular carcinoma cells HepG2 in vitro. MTT assay was used to detect the effects of different concentrations of PGF on the survival of HepG2 cells. The apoptosis rate and cell cycle distribution of HepG2 cells induced by PGF were detected by flow cytometry. The expressions of Bcl-2, Bax and Caspase3, Cyclin-A1 and Cyclin-B1 were detected by immunohistochemistry. Results: Compared with the control group, PGF could effectively decreased proliferation of human hepatoma HepG2 in a concentration-dependent manner. Cell cycle detection showed that the proportion of S phase in each group was 24.71%, 28.78%, 36.26 and 42.39%, respectively, indicating that cells were blocked in S phase. The immunocytochemical results showed that the expression of Cyclin A1 protein decreased significantly, and the expression of cyclin-B1 was not significantly different before and after treatment. Flow cytometry showed that the apoptosis rates in control group and PGF group were 0, 18.0%, 30.5% and 49.5%, respectively. The difference between PGF group and control group was significant. Immunocytochemical results showed that PGF could significantly inhibit the expression of mitochondrial apoptosis inhibitor Bcl-2, increase the expression of pro-apoptotic factor Bax in a concentration-dependent manner, and up-regulate the percentage of Bcl-2/Bax to induce apoptosis of hepatocellular carcinoma cells. Conclusion: PGF can inhibit the proliferation of human hepatoma HepG2 cells by inducing apoptosis, inhibiting the proliferation of cancer cells, blocking cell cycle, inhibiting the expression of Bcl-2, and upregulating the expression of Bax and Caspase3.
In recent years, the research of planetary exploration robots has become an active field. The jumping robot has become a hot spot in this field. This paper presents a work modelling and simulating a ...three-legged jumping robot, which has a powerful force, high leaping performance, and good flexibility. In particular, the jumping of the robot was simulated and the landing buffer of the robot was analyzed. Because this jumping robot lacks landing buffer, this paper verifies a method of absorbing landing kinetic energy to improve landing stability and storing it as the energy for the next jump in the simulation. Through the landing simulation, the factors affecting the landing energy absorption are identified. Moreover, the simulation experiment verifies that the application of the intermediate axis theorem helps to absorb more energy and adjust the landing attitude of the robot. The simulation results in this paper can be applied to the optimal design of robot prototypes and provide a theoretical basis for subsequent research.
Bladder cancer (BC) ranks the tenth in the incidence of global tumor epidemiology. LncRNAs and cuproptosis were discovered to regulate the cell death. Herein, we downloaded transcriptome profiling, ...mutational data, and clinical data on patients from The Cancer Genome Atlas (TCGA). High- and low-risk BC patients were categorized. Three CRLs (AL590428.1, AL138756.1 and GUSBP11) were taken into prognostic signature through least absolute shrinkage and selection operator (LASSO) Cox regression. Worse OS and PFS were shown in high-risk group (
< 0.05). ROC, independent prognostic analyses, nomogram and C-index were predicted
CRLs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated IncRNAs play a biological role in BC progression. Immune-related functions showed the high-risk group received more benefit from immunotherapy and had stronger immune responses, and the overall survival was better (
< 0.05). Finally, a more effective outcome (
< 0.05) was found from clinical immunotherapy
the TIDE algorithm and many potential anti-tumor drugs were identified. In our study, the cuproptosis-related signature provided a novel tool to predict the prognosis in BC patients accurately and provided a novel strategy for clinical immunotherapy and clinical applications.
Abstract
Background
Bladder cancer (BC) is one of the most common malignancies of the genitourinary system. Animal models offer an important tool to explore tumour initiation, progression, and ...therapeutic mechanisms. Our aim is to construct an optimized orthotopic BC model which is predictable, reproducible, and convenient.
Methods
The optimized orthotopic BC model was constructed in male C57BL/6 mice utilizing microsyringes to inoculate them with a murine BC cell line (MB49). Anesthetised mice were inoculated with an MB49 cell suspension (10 µL) at approximately 5 × 10
6
/mL. The whole process of modelling was observed and monitored every 3 days for 21 days utilizing HE staining and transabdominal ultrasonography (TUS).
Results
In this study, the model showed excellent success rates for tumour formation (96.67%) and metastatic rate (89.66%). Compared to the control group (sham operation), mice in the modelling group had serous cachexia, visible haematuresis and weight loss (all
P
< 0.05). The lungs, liver, ureter and kidneys were found to have tumour metastasis. Moreover, the average survival time (19.73 ± 1.69 d) of modelling mice was significantly shorter than that of the control mice (
P
< 0.05), which remained alive.
Conclusion
Our study established a method using microsyringes to inject murine BC cells into the bladder wall, creating a stable transplantable BC model in mice.
Bladder cancer, one of the most prevalent malignant cancers, has high rate of recurrence and metastasis. Owing to genomic instability and high-level heterogeneity of bladder cancer, chemotherapy and ...immunotherapy drugs sensitivity and lack of prognostic markers, the prognosis of bladder cancer is unclear. Necroptosis is a programmed modality of necrotic cell death in a caspase-independent form. Despite the fact that necroptosis plays a critical role in tumor growth, cancer metastasis, and cancer patient prognosis, necroptosis-related gene sets have rarely been studied in bladder cancer. As a result, the development of new necroptosis-related prognostic indicators for bladder cancer patients is critical. Herein, we assessed the necroptosis landscape of bladder cancer patients from The Cancer Genome Atlas database and classified them into two unique necroptosis-related patterns, using the consensus clustering. Then, using five prognosis-related genes, we constructed a prognostic model (risk score), which contained 5 genes (ANXA1, DOK7, FKBP10, MAP1B and SPOCD1). And a nomogram model was also developed to offer the clinic with a more useful prognostic indicator. We found that risk score was significantly associated with clinicopathological characteristics, TIME, and tumor mutation burden in patients with bladder cancer. Moreover, risk score was a valid guide for immunotherapy, chemotherapy, and targeted drugs. In our study, DOK7 was chosen to further verify our prognosis model, and functional assays indicated that knockdown the expression of DOK7 could prompt bladder cancer proliferation and migration. Our work demonstrated the potential role of prognostic model based on necroptosis genes in the prognosis, immune landscape and response efficacy of immunotherapy of bladder cancer.
Aβ40 and Aβ42 are the major forms of amyloid β peptides (Aβ) in the brain. Although Aβ42 differs from Aβ40 by only two residues, Aβ42 is much more prone to aggregation and more toxic to neurons than ...Aβ40. To probe whether dynamics contribute to such dramatic difference in function, backbone ps–ns dynamics of native Aβ monomers were characterized by
15N spin relaxation at 273.3 K and 800 MHz. Aβ42 aggregates much faster than Aβ40 in the NMR tube. The effect of Aβ aggregation was removed from the relaxation measurement by interleaved data collection.
R
1,
R
2 and nuclear Overhauser enhancement (NOE) values are similar in Aβ40 and Aβ42, except at the C terminus, indicating Aβ42 and Aβ40 monomers have identical global motions. Comparisons of the spectral density function
J(0.87ω
H) and order parameters (
S
2) indicate that the Aβ42 C terminus is more rigid than the Aβ40 C terminus. At 280.4 K and 287.6 K, the Aβ42 C terminus remains more rigid than the Aβ40 C terminus, suggesting such a dynamical difference is likely present at the physiological temperature. The Aβ42 monomer likely has less configurational entropy due to restricted motion in the C terminus and may pay a smaller entropic price to form fibrils than the Aβ40 monomer. We hypothesize that the entropic difference between Aβ40 and Aβ42 monomers might partly account for the fact that Aβ42 is the major Aβ species in parenchymal senile plaques in most Alzheimer's diseased brains in spite of the predominance of Aβ40 in plasma. The increased rigidity of the Aβ42 C terminus is likely due to its pre-ordering for β-conformation present in soluble oligomers and fibrils. The Aβ42 C terminus may therefore serve as an internal seed for aggregation.
PDF
