Computational drug repositioning and drug-target prediction have become essential tasks in the early stage of drug discovery. In previous studies, these two tasks have often been considered ...separately. However, the entities studied in these two tasks (i.e., drugs, targets, and diseases) are inherently related. On one hand, drugs interact with targets in cells to modulate target activities, which in turn alter biological pathways to promote healthy functions and to treat diseases. On the other hand, both drug repositioning and drug-target prediction involve the same drug feature space, which naturally connects these two problems and the two domains (diseases and targets). By using the wisdom of the crowds, it is possible to transfer knowledge from one of the domains to the other. The existence of relationships among drug-target-disease motivates us to jointly consider drug repositioning and drug-target prediction in drug discovery. In this paper, we present a novel approach called iDrug, which seamlessly integrates drug repositioning and drug-target prediction into one coherent model via cross-network embedding. In particular, we provide a principled way to transfer knowledge from these two domains and to enhance prediction performance for both tasks. Using real-world datasets, we demonstrate that iDrug achieves superior performance on both learning tasks compared to several state-of-the-art approaches. Our code and datasets are available at:
For decades, immunotherapies have offered hope for patients with advanced cancer. However, they show distinct benefits and limited clinical effects. Tumor vaccines have the potential to prime ...tumor-antigen-specific T cells and induce broad subsets of immune responses, ultimately eradicating tumor cells. Here, we classify tumor vaccines by their anti-tumor mechanisms, which include boosting the immune system, overcoming tumor immunosuppression, and modulating tumor angiogenesis. We focus on multidimensional tumor vaccine strategies using combinations of two or three of the above mechanisms, as these are superior to single-dimensional treatments. This review offers a perspective on tumor vaccine strategies and the future role of vaccine therapies in cancer treatment.
A simple calcination process was used to create g-C3N4 (CN) from melamine, and the modified g-C3N4 (MCN) was synthesized with hydrochloric acid (HCl), sulfuric acid (H2SO4), and nitric acid (HNO3). ...After acid modification, CN successfully introduced oxygen-containing functional groups and obtained CN-HNO3 with multiple holes, which improved the photocatalytic efficiency. The bandgap of CN-HNO3 (2.46 eV) is 0.24 eV lower than that of CN (2.70 eV), resulting in more electron holes and improved light absorption of the catalyst. CN-HNO3 has a conduction band (CB) of -1.23 eV, while CN has a CB of -1.13 eV. CN-HNO3 is simpler to convert O2 to and#183;O2- than CN, which can boost photocatalytic efficiency. The degradation of rhodamine B(RhB) was used to investigate the photocatalytic properties of CN and MCN. The results show that the photocatalytic efficiency of MCN was higher than that of pure CN, and the photocatalytic efficiency and degradation rate constant of CN-HNO3 was 36.6% and 5.5 times higher than that of the CN, reaching 99.7% and 0.0341 min-1. The degradation efficiency remained more than 85% after five cycles, showing that MCN was more photo-catalytically stable than CN.
In recent years, many studies have shown that the intestinal microflora has various effects that are linked to the critical physiological functions and pathological systems of the host. The ...intestinal microbial community is widely involved in the metabolism of food components such as protein, which is one of the essential nutrients in diets. Additionally, dietary protein/amino acids have been shown to have had a profound impact on profile and operation of gut microbiota. This review summarizes the current literature on the mutual interaction between intestinal microbiota and protein/amino acid metabolism for host mucosal immunity and health.
As one of the core technologies of electric vehicles (EVs), the state of charge (SOC) estimation algorithm of lithium-ion batteries is directly related to the performance of the battery management ...system (BMS). Before EVs are put into the market, the SOC estimation algorithm must be tested and verified to ensure the reliability of the BMS and the safe operation of EVs. Therefore, this paper establishes a lithium-ion batteries’ SOC estimation algorithm verification platform for the comprehensive performance evaluation and verification of the new SOC estimation algorithm. In addition, there are two schemes, including real-time SOC estimation verification and offline SOC estimation verification can be selected, which improve the reliability and efficiency of verification. Firstly, the design idea of the verification platform (the research and development purpose, functional requirements, and the overall design scheme) is introduced in detail. Secondly, the modular design idea is used to design the hardware structure of the verification platform, which mainly includes the BMS host module, BMS slave module, battery charger module, and electronic load module. Finally, the software system, including the communication architecture, the SOC reference standard and evaluation indexes of the algorithm, and the upper computer function and implementation is designed to realize the functions of the verification platform.
Purpose
Reactive lymphocytes are substantial components of germinoma, which are believed to be related to the favorable prognosis of this intracranial tumor and better response to immunotherapy. ...However, the mechanisms managing the recruitment of lymphocytes are poorly understood. High endothelial venules (HEVs) are specialized blood vessels that play key roles in lymphocyte trafficking in Lymph nodes. These vessels are associated with lymphocyte infiltration in chronic inflammatory diseases and various malignant tumors, but their distribution and implications in germinoma are unknown. This study aimed to investigate the distribution and implications of HEVs in intracranial germinomas.
Methods
We investigated the presence and distribution of HEVs in 42 germinomas by immunohistochemical staining of peripheral node addressin (PNAd) and transmission electron microscopic examination. The correlation of the densities of HEVs with the extent of T and B lymphocyte infiltration and several clinicopathological characteristics were also analyzed to determine whether HEVs are responsible for lymphocyte recruitment and their roles in anti‐tumor immunity in germinoma.
Results
PNAd‐positive HEVs were detected in 31% (13/42) of germinomas, and their presence correlated with abundant infiltrating CD3+ T cells, CD20 + B cells and CD8+ cytotoxic T lymphocytes (p = 0.0410, 0.0023, and 0.0061, respectively). Higher HEVs density was also correlated with several clinicopathological parameters, which are recognized indicators for favorable prognosis in germinomas, including typical tumor location (p = 0.0093), lower tumor cell content (p = 0.0428), and younger age at diagnosis (p = 0.0121). Furthermore, bioinformatics analysis showed HEVs‐associated genes mainly enriched in immune‐related Gene Ontology terms, including innate immune response, inflammatory response, and B cell receptor signaling pathway. The xCell analysis revealed that germinomas with higher HEVs enrichment scores had increased levels of the immune score, microenvironment score, dendritic cells, CD8+ central memory T‐cells, CD4+ memory T‐cells, and B‐cells.
Conclusions
Our findings indicate that HEVs could contribute to lymphocyte recruitment in germinomas, thus may serve as a predictor of favorable prognosis and better response to immunotherapy in this intracranial tumor.
The mechanical behaviors of rock masses are significantly affected by the distribution and shape of the holes in it. In this research, the fracture mechanism and the shear properties of rock masses ...containing holes were investigated by the cohesive zone model (CZM) method. At first, a uniaxial compression laboratory test was carried out, and some mechanical parameters were obtained, and then the obtained mechanical parameters were used to build a mathematical model with zero-thickness elements. Subsequently, the numerical shear test was performed under a mixed-mode test, using the obtained mechanical parameters. Finally, the mechanical characteristics and crack behaviors were discussed separately. The results exhibit that the shear process in this research could be determined and identified as the elastic, strengthening, plastic, and residual stress stages, respectively. Note that the shear rate and normal stress of rock masses containing holes are significantly and positively correlated with their shear strength and dilatancy. In addition, the cracking behavior and mechanical properties of the specimens are closely related to the shear rate and normal stress. Overall, the results of this study have great significance in guiding future, in-depth research of rock masses containing holes in rock slopes.
IDH-mutant lower-grade gliomas (LGGs, grade 2 or 3) eventually transform into secondary grade 4 astrocytomas (sA
). Here, we sought to describe the transformation time, risk factors, and outcomes in ...malignant transformation of IDH-mutant LGGs.
We screened data for 108 patients with sA
in the Chinese Glioma Genome Atlas who had initial IDH-mutant LGGs and underwent reoperation during 2005-2021. We evaluated the transformation time from IDH-mutant LGGs to sA
, and associated risk factors and outcomes. Malignant transformation was defined as pathological confirmation of grade 4 astrocytoma.
The median age of the 108 patients with IDH-mutant LGGs was 35 years (range, 19-54); the median age at transformation was 40 years (range, 25-62); and the median follow-up time for all patients was 146 months (range, 121-171). The average transformation time was 58.8 months for all patients with LGGs (range, 5.9-208.1); 63.5 and 51.9 months for grade 2 and 3 gliomas, respectively; and 58.4 and 78.1 months for IDH-mutant/1p/19q-non-codeleted astrocytomas and IDH-mutant/1p/19q-codeleted oligodendrogliomas, respectively. Univariate and multivariate analysis indicated that radiotherapy hazard ratio (HR), 0.29; 95% confidence interval (CI), 0.137-0.595;
= 0.001 and non-A blood type (HR, 0.37; 95% CI, 0.203-0.680;
= 0.001) were protective factors against delayed malignant transformation. Radiotherapy was associated with improved survival after transformation (HR, 0.44; 95% CI, 0.241-0.803;
= 0.008), overall survival (HR, 0.50; 95% CI, 0.265-0.972;
= 0.041), and progression-free survival (HR, 0.25; 95% CI, 0.133-0.479;
< 0.0001) in patients with IDH-mutant gliomas.
Radiotherapy is associated with delayed malignant transformation and improved survival in patients with IDH-mutant gliomas.
Human cancer statistics show that an increased incidence of urologic cancers such as bladder cancer, prostate cancer, and renal cell carcinoma. Due to the lack of early markers and effective ...therapeutic targets, their prognosis is poor. Fascin-1 is an actin-binding protein, which functions in the formation of cell protrusions by cross-linking with actin filaments. Studies have found that fascin-1 expression is elevated in most human cancers and is related to outcomes such as neoplasm metastasis, reduced survival, and increased aggressiveness. Fascin-1 has been considered as a potential therapeutic target for urologic cancers, but there is no comprehensive review to evaluate these studies. This review aimed to provide an enhanced literature review, outline, and summarize the mechanism of fascin-1 in urologic cancers and discuss the therapeutic potential of fascin-1 and the possibility of its use as a potential marker. We also focused on the correlation between the overexpression of fascin-1 and clinicopathological parameters. Mechanistically, fascin-1 is regulated by several regulators and signaling pathways (such as long noncoding RNA, microRNA, c-Jun N-terminal kinase, and extracellular regulated protein kinases). The overexpression of fascin-1 is related to clinicopathologic parameters such as pathological stage, bone or lymph node metastasis, and reduced disease-free survival. Several fascin-1 inhibitors (G2, NP-G2-044) have been evaluated in vitro and in preclinical models. The study proved the promising potential of fascin-1 as a newly developing biomarker and a potential therapeutic target that needs further investigation. The data also highlight the inadequacy of fascin-1 to serve as a novel biomarker for prostate cancer.
As the development of the multi-energy system (MES), various ME applications are deployed. ME applications not only bring advanced functionalities to the MES, but also show great potentials in ...promoting the operation performance of the MES, especially improving the accommodation of renewable energy sources (RES). However, the realization of these potentials largely relies on the energy management, which shall facilitate the effective function of each ME application and the coordinated collaboration of all the ME applications. Without a comprehensive energy management methodology, ME applications may mutually interfere, which not only hinder the RES utilization, but also may harm the MES operation performance. In this premise, this paper integrates the energy management model of the combined cooling, heat and power plants, power-to-hydrogen/gas-to-power plants, and demand side management model of the EV charging loads into the energy management model of the MES, and proposes an comprehensive optimal day-ahead energy management framework to simultaneously improve the profit, RES utilization rate, and energy saving performance of the MES. To address the proposed optimization model, Elitist Non-dominated Sorting Genetic algorithm II algorithm is employed to heuristically find the Pareto-optimal results. Finally, case studies prove the effectiveness of the proposed methodology.
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