Uncertainty is a significant challenge in tsunami hazard analysis. Tsunami heights are affected by complex factors and change constantly during propagation. The heights of tsunami have random ...characteristics. This study proposes that the water depths (related to seabed topography) are the most important factors that affect tsunami height. But across the globe, a considerable area of seabed topography has not been measured. So it is necessary to use the method of uncertainty to consider the water depth. The Wiener process is utilized to quantify the random changes of the water depth, which can better describe the situation that water depths change in a non-monotonic way. Considering the uncertainty of water depth, a Weiner process-based probabilistic model was established for predicting the maximum tsunami height, which is different from the maximum tsunami height deterministic or stochastic model previously studied with higher prediction efficiency and good prediction accuracy. The probability distribution of maximum tsunami heights was calculated using the stochastic model. The mean value of the maximum tsunami heights was very similar to the average value of 165 actual observations of maximum tsunami heights collected from 1997 to 2017.
There are many factors leading to construction safety accident. The rule presented under the influence of these factors should be a statistical random rule. To reveal those random rules and study the ...probability prediction method of construction safety accident, according to stochastic process theory, general stochastic process, Markov process and normal process are respectively used to simulate the risk-accident process in this paper. First, in the general-random-process-based analysis the probability of accidents in a period of time is calculated. Then, the Markov property of the construction safety risk evolution process is illustrated, and the analytical expression of probability density function of first-passage time of Markov-based risk-accident process is derived to calculate the construction safety probability. In the normal-process-based analysis, the construction safety probability formulas in cases of stationary normal risk process and non-stationary normal risk process with zero mean value are derived respectively. Finally, the number of accidents that may occur on construction site in a period is studied macroscopically based on Poisson process, and the probability distribution of time interval between adjacent accidents and the time of the nth accident are calculated respectively. The results provide useful reference for the prediction and management of construction accidents.
Tethering a metal complex to its phosphate counterion via a phosphine ligand enables a new strategy in asymmetric counteranion-directed catalysis (ACDC). A straightforward, scalable synthetic route ...gives access to the gold(I) complex of a phosphine displaying a chiral phosphoric acid function. The complex generates a catalytically active species with an unprecedented intramolecular relationship between the cationic Au(I) center and the phosphate counterion. The benefits of tethering the two functions of the catalyst are demonstrated here in a tandem cycloisomerization/nucleophilic addition reaction, by attaining high enantioselectivity levels (up to 97% ee) at an unusually low 0.2 mol % catalyst loading. Remarkably, the method is also compatible with a silver-free protocol.
Human epigenome and transcription activities have been characterized by a number of sequence-based deep learning approaches which only utilize the DNA sequences. However, transcription factors ...interact with each other, and their collaborative regulatory activities go beyond the linear DNA sequence. Therefore leveraging the informative 3D chromatin organization to investigate the collaborations among transcription factors is critical. We developed ECHO, a graph-based neural network, to predict chromatin features and characterize the collaboration among them by incorporating 3D chromatin organization from 200-bp high-resolution Micro-C contact maps. ECHO predicted 2,583 chromatin features with significantly higher average AUROC and AUPR than the best sequence-based model. We observed that chromatin contacts of different distances affected different types of chromatin features' prediction in diverse ways, suggesting complex and divergent collaborative regulatory mechanisms. Moreover, ECHO was interpretable via gradient-based attribution methods. The attributions on chromatin contacts identify important contacts relevant to chromatin features. The attributions on DNA sequences identify TF binding motifs and TF collaborative binding. Furthermore, combining the attributions on contacts and sequences reveals important sequence patterns in the neighborhood which are relevant to a target sequence's chromatin feature prediction.
NOTCH Signaling in Osteosarcoma Zhang, Zhenhao; Wu, Wei; Shao, Zengwu
Current Issues in Molecular Biology,
03/2023, Letnik:
45, Številka:
3
Journal Article
Recenzirano
Odprti dostop
The combination of neoadjuvant chemotherapy and surgery has been promoted for the treatment of osteosarcoma; however, the local recurrence and lung metastasis rates remain high. Therefore, it is ...crucial to explore new therapeutic targets and strategies that are more effective. The NOTCH pathway is not only involved in normal embryonic development but also plays an important role in the development of cancers. The expression level and signaling functional status of the NOTCH pathway vary in different histological types of cancer as well as in the same type of cancer from different patients, reflecting the distinct roles of the Notch pathway in tumorigenesis. Studies have reported abnormal activation of the NOTCH signaling pathway in most clinical specimens of osteosarcoma, which is closely related to a poor prognosis. Similarly, studies have reported that NOTCH signaling affected the biological behavior of osteosarcoma through various molecular mechanisms. NOTCH-targeted therapy has shown potential for the treatment of osteosarcoma in clinical research. After the introduction of the composition and biological functions of the NOTCH signaling pathway, the review paper discussed the clinical significance of dysfunction in osteosarcoma. Then the paper reviewed the recent relevant research progress made both in the cell lines and in the animal models of osteosarcoma. Finally, the paper explored the potential of the clinical application of NOTCH-targeted therapy for the treatment of osteosarcoma.
•XGBoost model accurately estimated aboveground biomass in grasslands.•Biomass increased with increases in temperature and precipitation.•New and effective method for estimating aboveground biomass ...in Inner Mongolia.
Aboveground biomass (AGB) is a key index that reflects grassland health and is of great importance for grassland conservation and sustainable utilization. Many previous studies on grassland AGB were based on the analysis of the whole study period, can’t reflect the change of grassland in the short term, which was not conducive to the implementation and revision of policies. And it is still a challenge to accurately describe the response of grassland AGB to climate factors. In this study, we used four machine learning algorithms (kNN, k-nearest neighbor; RF, Random Forest; SVR, Support Vactor Regression; and XGBoost, eXtreme Gradient Boosting) to construct the estimation model of grassland AGB in eastern Inner Mongolia based on grassland AGB measurement data, MODIS(MOD13Q1) data and environmental data (climate and topography). The average distribution of grassland AGB from 2003 to 2021 was calculated based on the optimal grassland AGB estimation model. The changes of grassland AGB from 2003 to 2021 and in every five-year period during the study series were comprehensively analyzed by the Theil–Sen Median trend analysis and the Mann–Kendall test. The response of grassland AGB to climatic factors was investigated using sensitivity analysis. The results showed that (1) the XGBoost model constructed by NDVI, longitude, latitude, temperature, precipitation, elevation, slope, and aspect (NXYTPESA) is the optimal grassland AGB model (R2 = 0.87, RMSE = 14.27 g/m2). (2) The 20-year average grassland AGB in Eastern Inner Mongolia showed heterogeneous, with higher values in the northeast and lower values in the southwest. (3) The inter-annual variation fluctuated substantially, and the overall trend was increasing. Compared with other time periods, most grassland AGBs were in an increasing trend during 2008–2012 (79 %) and 2018–2021 (84 %). (4) The grassland AGB in the study area was regulated by temperature and precipitation, and the influence of precipitation was greater than that of temperature. This study provides a new method for estimating grassland AGB and its changes and a scientific basis for the sustainable development of grassland ecosystems in eastern Inner Mongolia.
The shortage of water resources is a crisis for human ecosystems. Compared with other ecosystems, the impact on agricultural ecosystems is more prominent. In order to alleviate this situation, a new ...type of agricultural hydrogel, agarose-bacterial cellulose hydrogel, was synthesized by replacing the traditional petroleum-based monomer with natural polysaccharide. Bacterial cellulose was used as raw material for the synthesis of hydrogels using agarose as matrix template and N, N’- methylenebisacrylamide as cross-linkers. In the present study, the hydrogel has optimized the ratio of the three synthesized polymers and characterized this hydrogel using FTIR spectra, XRD, and SEM. The findings demonstrated that bacterial cellulose was adequately incorporated into the agarose hydrogel and that the pores of AB1 were more significant than those of AA and AB2, which provided crucial support for the hydrogel’s ability to encourage plant development. By mixing hydrogel with soil, the effects of soil which have composite hydrogel and without composite hydrogel on plant germination and growth were studied. The results showed that adding bacterial cellulose increased the water retention and holding capacity of agarose hydrogel. Moreover, the plant germination rate and growing trend in soil with hydrogel were better than those without hydrogel. This low-cost, quickly made hydrogel has great application potential in agricultural soil.
SGLT2 (sodium-glucose cotransporter 2) is an important mediator of epithelial glucose transport and has been reported that SGLT2, robustly and diffusely expressed in malignant cancer cells, was ...overexpressed in various tumors, and inhibiting the SGLT2 expression significantly inhibited tumor progression. By blocking the functional activity of SGLT2, SGLT2 inhibitors have shown anticancer effects in several malignant cancers, including breast cancer, cervical cancer, hepatocellular cancer, prostate cancer, and lung cancer. However, the anticancer effect of SGLT2 inhibitors in osteosarcoma and the specific mechanism are still unclear. In the present study, we found that SGLT2 was overexpressed at the protein level in osteosarcoma. Furthermore, our results showed that the SGLT2 inhibitor significantly inhibited osteosarcoma tumor growth and induced infiltration of immune cells in vivo by upregulating STING expression and activating the IRF3/IFN-β pathway, which could attribute to the suppression of AKT phosphorylation. In addition, the combined treatment with SGLT2 inhibitor and STING agonist 2'3'-cGAMP exerted synergistic antitumor effects in osteosarcoma. Furthermore, the overexpression of SGLT2 at the protein level was correlated with the degradation of SGLT2 induced by TRIM21. This result demonstrated that SGLT2 is a novel therapeutic target of osteosarcoma, and that the SGLT2 inhibitor, especially in combination with 2'3'-cGAMP, is a potential therapeutic drug.
Background
Tumor‐induced osteomalacia (TIO) belongs to a rare disease of the paraneoplastic syndrome. Phosphate uric mesenchymal tumor (PMT) is the most common cause of TIO, while the possibility of ...other tumors cannot be excluded.
Case presentation
We present a case of a 36‐year‐old female patient with systemic skeletal abnormalities. The woman complained of low back pain with mild motor dysfunction for 2 years. Laboratory examination showed abnormalities in markers of bone metabolism, parathyroid hormone (PTH), vitamin D and serum phosphorus. Pooled imaging examination indicated extension abnormalities in the skeletal system and a single lesion in the right femoral head. The lesion of the right femoral was imaging with somatostatin receptor‐positive, which was highly suggestive of a single neuroendocrine tumor. CT guided right femoral tumorectomy and bone grafting were performed when medical treatment failed. Postoperative pathological diagnosis was phosphate urinary mesenchymal tumor secreting fibroblast growth factor 23 (FGF23), which accorded with pre‐operative expectations. The postoperative symptoms were effectively relieved, and indicators returned to normal.
Conclusion
The tumors causing TIO exhibited significant heterogeneity in terms of tissue origin, pathological characteristics and biological behavior, but the unique common characteristic is the secretion of FGF23. With significant progress in diagnosis and treatment, the clinical follow‐up of most TIO patients shows a good prognosis, but the prognosis of those with malignant tumors is relatively poor.
We presented and analyzed a case of tumor‐induced osteomalacia (TIO) caused by the single phosphate urinary mesenchymal tumor secreting fibroblast growth factor 23 (FGF23) in the right femoral head. The tumors causing TIO exhibited significant heterogeneity and the prognosis of patients with malignant tumors is relatively poor.
To explore the crystalline arrangement of the alloy and the processes involving iron (Fe) precipitation, we employed molecular dynamics simulation with a cooling rate of 2 × 10
for Cu
Fe
(where X ...represents 1%, 3%, 5%, and 10%) alloy. The results reveal that when the Fe content was 1%, Fe atoms consistently remained uniformly distributed as the temperature of the alloy decreased. Further, there was no Fe atom aggregation phenomenon. The crystal structure was identified as an FCC-based Cu crystal, and Fe atoms existed in the matrix in solid solution form. When the Fe content was 3%, Fe atoms tended to aggregate with the decreasing temperature of the alloy. Moreover, the proportion of BCC crystal structure exhibited no obvious changes, and the crystal structure remained FCC-based Cu crystal. When the Fe content was between 5% and 10%, the Fe atoms exhibited obvious aggregation with the decreasing temperature of the alloy. At the same time, the aggregation phenomenon was found to be more significant with a higher Fe content. Fe atom precipitation behaviour can be delineated into three distinct stages. The initial stage involves the gradual accumulation of Fe clusters, characterised by a progressively stable cluster size. This phenomenon arises due to the interplay between atomic attraction and the thermal motion of Fe-Fe atoms. In the second stage, small Fe clusters undergo amalgamation and growth. This growth is facilitated by non-diffusive local structural rearrangements of atoms within the alloy. The third and final stage represents a phase of equilibrium where both the size and quantity of Fe clusters remain essentially constant following the crystallisation of the alloy.
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