A novel lysosome-related gene signature coupled with gleason score for prognosis prediction in prostate cancer

Background: Prostate cancer (PCa) is highly heterogeneous, which makes it difficult to precisely distinguish the clinical stages and histological grades of tumor lesions, thereby leading to large amounts of under- and over-treatment. Thus, we expect the development of novel prediction approaches for the prevention of inadequate therapies. The emerging evidence demonstrates the pivotal role of lysosome-related mechanisms in the prognosis of PCa. In this study, we aimed to identify a lysosome-related prognostic predictor in PCa for future therapies.Methods: The PCa samples involved in this study were gathered from The Cancer Genome Atlas database (TCGA) (n = 552) and cBioPortal database (n = 82). During screening, we categorized PCa patients into two immune groups based on median ssGSEA scores. Then, the Gleason score and lysosome-related genes were included and screened out by using a univariate Cox regression analysis and the least absolute shrinkage and selection operation (LASSO) analysis. Following further analysis, the probability of progression free interval (PFI) was modeled by using unadjusted Kaplan–Meier estimation curves and a multivariable Cox regression analysis. A receiver operating characteristic (ROC) curve, nomogram and calibration curve were used to examine the predictive value of this model in discriminating progression events from non-events. The model was trained and repeatedly validated by creating a training set (n = 400), an internal validation set (n = 100) and an external validation (n = 82) from the cohort.Results: Following grouping by ssGSEA score, the Gleason score and two LRGs—neutrophil cytosolic factor 1 (NCF1) and gamma-interferon-inducible lysosomal thiol reductase (IFI30)—were screened out to differentiate patients with or without progression (1-year AUC = 0.787; 3-year AUC = 0.798; 5-year AUC = 0.772; 10-year AUC = 0.832). Patients with a higher risk showed poorer outcomes (p < 0.0001) and a higher cumulative hazard (p < 0.0001). Besides this, our risk model combined LRGs with the Gleason score and presented a more accurate prediction of PCa prognosis than the Gleason score alone. In three validation sets, our model still achieved high prediction rates.Conclusion: In conclusion, this novel lysosome-related gene signature, coupled with the Gleason score, works well in PCa for prognosis prediction

‘ZhongPan 101’ and ‘ZhongPan 102’: Two Flat Peach Cultivars From China

Flat peach [Prunus persica (L.) Batsch var. platycarpa] is a variant of ordinary peach with a unique flat shape. It is well known for its shape and delicious fruits (Miao et al. 2022). Although flat peach has a long history of cultivation in China, until the beginning of the 20th century, flat peach was only distributed as a minor variety in the main peach-producing areas of China. In terms of flat peach cultivars, only 46 of the 709 peach cultivars listed in Peach Genetic Resource in China (Wang et al. 2012) are flat peach cultivars, and most of them are flat landraces. Several problems have been noted previously in flat peach cultivars, including poor closure of the blossom end (blossom-end scarring in mild cases and cracking in severe cases), cracked stone in some cultivars (loss of commercial value in severe cases), nonsymmetrical fruit shape, small flesh, and low yield (Wang 2021). Many of the shortcomings of flat peach cultivars are intrinsic problems of the cultivars, which are difficult to improve through cultivation measures. This is the key factor limiting the large-scale promotion of flat peach cultivation in China. For many years, peach breeders in China have been devoted to the genetic improvement of flat peach, and some improved flat peach cultivars have been released, for instance, ‘Pocket Zaoban’ (Jiang et al. 2007) and ‘124 Pantao’ (Ma et al. 2003). However, problems persist in these cultivars, including small fruits, soft flesh, and blossom-end cracks. Only a few flat peach cultivars have good overall performance. In recent years, the Zhengzhou Fruit Research Institute (ZFRI), Chinese Academy of Agricultural Sciences (CAAS), identified genetic sources of flat peach with slow or nonmelting flesh, a well-closed blossom end, and little or no cracking. They were hybridized with high-quality peach and nectarine cultivars or selections. After multiple generations of improvement, breakthroughs were made in early flat peach breeding, and a series of flat peach cultivars with excellent comprehensive traits have been produced. These cultivars are favored by fruit farmers in the main peach-producing areas in China. Hence, the main problems in flat peach cultivation are expected to be solved, which will help expand the cultivation area of flat peach. ‘ZhongPan 101’ and ‘ZhongPan 102’ are two yellow-flesh flat peach cultivars 45 released from the ZFRI, CAAS. These two cultivars produce large, well-shaped, high-quality fruits with a completely closed stylar end and high yield. Three years of evaluation has confirmed that the peach trees of the two cultivars are stable. ‘ZhongPan 101’ and ‘ZhongPan 102’ were well adapted to climate of the middle and lower reaches of the Yellow River; have performed well in Henan, Jiangsu, and Anhui Provinces; and are suggested for trial wherever ‘ZhongYouPan 9’ is grown

AAV-CRISPR/Cas9–Mediated Depletion of VEGFR2 Blocks Angiogenesis In Vitro

Purpose Pathologic angiogenesis is a component of many diseases, including neovascular age-related macular degeneration, proliferation diabetic retinopathy, as well as tumor growth and metastasis. The purpose of this project was to examine whether the system of adeno-associated viral (AAV)–mediated CRISPR (clustered regularly interspaced short palindromic repeats)–associated endonuclease (Cas)9 can be used to deplete expression of VEGF receptor 2 (VEGFR2) in human vascular endothelial cells in vitro and thus suppress its downstream signaling events. Methods: The dual AAV system of CRISPR/Cas9 from Streptococcus pyogenes (AAV-SpGuide and -SpCas9) was adapted to edit genomic VEGFR2 in primary human retinal microvascular endothelial cells (HRECs). In this system, the endothelial-specific promoter for intercellular adhesion molecule 2 (ICAM2) was cloned into the dual AAV vectors of SpGuide and SpCas9 for driving expression of green fluorescence protein (GFP) and SpCas9, respectively. These two AAV vectors were applied to production of recombinant AAV serotype 5 (rAAV5), which were used to infect HRECs for depletion of VEGFR2. Protein expression was determined by Western blot; and cell proliferation, migration, as well as tube formation were examined. Results: AAV5 effectively infected vascular endothelial cells (ECs) and retinal pigment epithelial (RPE) cells; the ICAM2 promoter drove expression of GFP and SpCas9 in HRECs, but not in RPE cells. The results showed that the rAAV5-CRISPR/Cas9 depleted VEGFR2 by 80% and completely blocked VEGF-induced activation of Akt, and proliferation, migration as well as tube formation of HRECs. Conclusions: AAV-CRISRP/Cas9–mediated depletion of VEGFR2 is a potential therapeutic strategy for pathologic angiogenesis

Upconversion NIR-II fluorophores for mitochondria-targeted cancer imaging and photothermal therapy

Acknowledgements: The work was supported by the National Key R&D Program of China (2020YFA0908800), NSFC (81773674, 81573383), Shenzhen Science and Technology Research Grant (JCYJ20190808152019182), Hubei Province Scientific and Technical Innovation Key Project, National Natural Science Foundation of Hubei Province (2017CFA024, 2017CFB711), the Applied Basic Research Program of Wuhan Municipal Bureau of Science and Technology (2019020701011429), Tibet Autonomous Region Science and Technology Plan Project Key Project (XZ201901-GB-11), the Local Development Funds of Science and Technology Department of Tibet (XZ202001YD0028C), Project First-Class Disciplines Development Supported by Chengdu University of Traditional Chinese Medicine (CZYJC1903), Health Commission of Hubei Province Scientific Research Project (WJ2019M177, WJ2019M178), the China Scholarship Council, and the Fundamental Research Funds for the Central Universities.Peer reviewedPublisher PD

Effects of partner proteins on BCA2 RING ligase activity

Abstract Background BCA2 is an E3 ligase linked with hormone responsive breast cancers. We have demonstrated previously that the RING E3 ligase BCA2 has autoubiquitination activity and is a very unstable protein. Previously, only Rab7, tetherin, ubiquitin and UBC9 were known to directly interact with BCA2. Methods Here, additional BCA2 binding proteins were found using yeast two-hybrid and bacterial-II-hybrid screening techniques with Human breast and HeLa cDNA libraries. Co-expression of these proteins was analyzed through IHC of TMAs. Investigation of the molecular interactions and effects were examined through a series of in vivo and in vitro assays. Results Ten unique BCA2 interacting proteins were identified, two of which were hHR23a and 14-3-3sigma. Both hHR23a and 14-3-3sigma are co-expressed with BCA2 in breast cancer cell lines and patient breast tumors (n = 105). hHR23a and BCA2 expression was significantly correlated (P = \u3c 0.0001 and P = 0.0113) in both nucleus and cytoplasm. BCA2 expression showed a statistically significant correlation with tumor grade. High cytoplasmic hHR23a trended towards negative nodal status. Binding to BCA2 by hHR23a and 14-3-3sigma was confirmed in vitro using tagged partner proteins and BCA2. hHR23a and 14-3-3sigma effect the autoubiquitination and auto-degradation activity of BCA2. Ubiquitination of hHR23a-bound BCA2 was found to be dramatically lower than that of free BCA2, suggesting that hHR23a promotes the stabilization of BCA2 by inactivating its autoubiquitination activity, without degradation of hHR23a. On the other hand, phosphorylated BCA2 protein is stabilized by interaction with 14-3-3sigma both with and without proteasome inhibitor MG-132 suggesting that BCA2 is regulated by multiple degradation pathways. Conclusions The interaction between BCA2 and hHR23a in breast cancer cells stabilizes BCA2. High expression of BCA2 is correlated with grade in breast cancer, suggesting regulation of this E3 ligase is important to cancer progression

A New Lightweight Convolutional Neural Network for Multi-Scale Land Surface Water Extraction from GaoFen-1D Satellite Images

Mapping land surface water automatically and accurately is closely related to human activity, biological reproduction, and the ecological environment. High spatial resolution remote sensing image (HSRRSI) data provide extensive details for land surface water and gives reliable data support for the accurate extraction of land surface water information. The convolutional neural network (CNN), widely applied in semantic segmentation, provides an automatic extraction method in land surface water information. This paper proposes a new lightweight CNN named Lightweight Multi-Scale Land Surface Water Extraction Network (LMSWENet) to extract the land surface water information based on GaoFen-1D satellite data of Wuhan, Hubei Province, China. To verify the superiority of LMSWENet, we compared the efficiency and water extraction accuracy with four mainstream CNNs (DeeplabV3+, FCN, PSPNet, and UNet) using quantitative comparison and visual comparison. Furthermore, we used LMSWENet to extract land surface water information of Wuhan on a large scale and produced the land surface water map of Wuhan for 2020 (LSWMWH-2020) with 2m spatial resolution. Random and equidistant validation points verified the mapping accuracy of LSWMWH-2020. The results are summarized as follows: (1) Compared with the other four CNNs, LMSWENet has a lightweight structure, significantly reducing the algorithm complexity and training time. (2) LMSWENet has a good performance in extracting various types of water bodies and suppressing noises because it introduces channel and spatial attention mechanisms and combines features from multiple scales. The result of land surface water extraction demonstrates that the performance of LMSWENet exceeds that of the other four CNNs. (3) LMSWENet can meet the requirement of high-precision mapping on a large scale. LSWMWH-2020 can clearly show the significant lakes, river networks, and small ponds in Wuhan with high mapping accuracy

Histogram Publication over Numerical Values under Local Differential Privacy

Local differential privacy has been considered the standard measurement for privacy preservation in distributed data collection. Corresponding mechanisms have been designed for multiple types of tasks, like the frequency estimation for categorical values and the mean value estimation for numerical values. However, the histogram publication of numerical values, containing abundant and crucial clues for the whole dataset, has not been thoroughly considered under this measurement. To simply encode data into different intervals upon each query will soon exhaust the bandwidth and the privacy budgets, which is infeasible for real scenarios. Therefore, this paper proposes a highly efficient framework for differentially private histogram publication of numerical values in a distributed environment. The proposed algorithms can efficiently adopt the correlations among multiple queries and achieve an optimal resource consumption. We also conduct extensive experiments on real-world data traces, and the results validate the improvement of proposed algorithms

Investigation on Eigenfrequency of a Cylindrical Shell Resonator under Resonator-Top Trimming Methods

The eigenfrequency of a resonator plays a significant role in the operation of a cylindrical shell vibrating gyroscope, and trimming is aimed at eliminating the frequency split that is the difference of eigenfrequency between two work modes. In this paper, the effects on eigenfrequency under resonator-top trimming methods that trim the top of the resonator wall are investigated by simulation and experiments. Simulation results show that the eigenfrequency of the trimmed mode increases in the holes-trimming method, whereas it decreases in the grooves-trimming method. At the same time, the untrimmed modes decrease in both holes-trimming and grooves-trimming methods. Moreover, grooves-trimming is more efficient than holes-trimming, which indicates that grooves-trimming can be a primary trimming method, and holes-trimming can be a precision trimming method. The rigidity condition after grooves-trimming is also studied to explain the variation of eigenfrequency. A femtosecond laser is employed in the resonator trimming experiment by the precise ablation of the material. Experimental results are in agreement with the simulation results