Search

Intraperitoneal dissemination is the main method of epithelial ovarian cancer (EOC) metastasis, which is related to poor prognosis and a high recurrence rate. Circular RNAs (circRNAs) are a novel class of endogenous RNAs with covalently closed loop structures that are implicated in the regulation of tumor development. In this study, hsa_circ_0001546 is downregulated in EOC primary and metastatic tissues vs. control tissues and this phenotype has a favorable effect on EOC OS and DFS. hsa_circ_0001546 can directly bind with 14‐3‐3 proteins to act as a chaperone molecule and has a limited positive effect on 14‐3‐3 protein stability. This complex recruits CAMK2D to induce the Ser324 phosphorylation of Tau proteins, changing the phosphorylation status of Tau bound to 14‐3‐3 and ultimately forming the hsa_circ_0001546/14‐3‐3/CAMK2D/Tau complex. The existence of this complex stimulates the production of Tau aggregation, which then induces the accumulation of lipid peroxides (LPOs) and causes LPO‐dependent ferroptosis. In vivo, treatment with ferrostatin‐1 and TRx0237 rescued the inhibitory effect of hsa_circ_0001546 on EOC cell spreading. Therefore, based on this results, ferroptosis caused by Tau aggregation occurs in EOC cells, which is not only in Alzheimer's disease‐ or Parkinson's disease‐related cells and this kind of ferroptosis driven by the hsa_circ_0001546/14‐3‐3/CAMK2D/Tau complex is LPO‐dependent rather than GPX4‐dependent is hypothesized. [ABSTRACT FROM AUTHOR]

Nature‐inspired supramolecular self‐assemblies are attractive photocatalysts, but their quantum yields are limited by poor charge separation and transportation. A promising strategy for efficient charge transfer is to enhance the built‐in electric field by symmetry breaking. Herein, an unsymmetric protonation, N‐heterocyclic π‐conjugated anthrazoline‐based supramolecular photocatalyst SA‐DADK‐H+ was developed. The unsymmetric protonation breaks the initial structural symmetry of DADK, resulting in ca. 50‐fold increase in the molecular dipole, and facilitates efficient charge separation and transfer within SA‐DADK‐H+. The protonation process also creates numerous active sites for H2O adsorption, and serves as crucial proton relays, significantly improving the photocatalytic efficiency. Remarkably, SA‐DADK‐H+ exhibits an outstanding hydrogen evolution rate of 278.2 mmol g−1 h−1 and a remarkable apparent quantum efficiency of 25.1 % at 450 nm, placing it among the state‐of‐the‐art performances in organic semiconductor photocatalysts. Furthermore, the versatility of the unsymmetric protonation approach has been successfully applied to four other photocatalysts, enhancing their photocatalytic performance by 39 to 533 times. These findings highlight the considerable potential of unsymmetric protonation induced symmetry breaking strategy in tailoring supramolecular photocatalysts for efficient solar‐to‐fuel production. [ABSTRACT FROM AUTHOR]

Introduction: Soil salinity-alkalinity has emerged as a global problem affecting many ecosystems, including grassland. Plants evolve into different ecotypes to adapt to various environments. Leymus chinensis widely distributed in the eastern Eurasian steppe, has evolved into two main ecotypes: yellow-green (YG) and gray-green (GG). Studies on the adaption mechanisms of both ecotypes in response to saline-alkaline stress are limited. Methods: In this study, the growth and physiological traits of ecotypes YG and GG in soils with different salinity-alkalinity levels-severe saline-alkaline soil (SS), moderate saline-alkaline soil (MS), and light saline-alkaline soil (LS)-were studied. After exposure to saline-alkaline stress for 15 months, the L. chinensis ecotypes exhibited significant differences in the growth characteristics. Results: The specific leaf area, individual tiller biomass, net photosynthetic rate, and potassium content of the two ecotypes under MS conditions were significantly higher than or similar to those under LS conditions. This indicates that L chinensis showed a certain degree of tolerance to saline-alkaline environments under MS conditions. Saline-alkaline stress increased the tillers by 56% in GG and reduced them by 26% in YG, and did not alter the SLA and the number of individual tiller leaves of GG but reduced that of YG. Moreover, with increasing levels of saline-alkaline stress, ecotype GG exhibited an increase in net photosynthetic rate (Pn), while ecotype YG showed insignificant changes. Under SS, GG exhibited higher Pn and chlorophyll content than YG. Additionally, with the increase in the saline-alkaline stress level, the Na+ content increased, but GG exhibited a significantly lower Na+ content than YG. Conversely, the K+ and Ca2+ contents and the K+/Na+ and Ca2+/Na+ ratios decreased, but GG exhibited higher values than YG. Discussion: GG reduced Na+ by absorption by increasing tillers. Additionally, GG absorbed more K+ and Ca2+ ions, thereby maintaining higher K+/Na+ and Ca2+/ Na+ ratios than YG under saline-alkaline stress. These adaptive strategies enable ecotype GG to grow and maintain normal physiological functions under high saline-alkaline stress. The findings of this study hold practical significance for enhancing the economic and ecological value of saline-alkaline grasslands. [ABSTRACT FROM AUTHOR]

Genetic factors play significant roles in the tumorigenicity of lung cancer; however, there is lack of systematic and large‐scale characterization of pathogenic germline variants for lung cancer. In this study, germline variants in 146 preselected cancer‐susceptibility genes were detected in 17 904 Chinese lung cancer patients by clinical next‐generation sequencing. Among 17 904 patients, 1738 patients (9.7%) carried 1840 pathogenic/likely pathogenic (P/LP) variants from 87 cancer‐susceptibility genes. SBDS (SBDS ribosome maturation factor) (1.37%), TSHR (thyroid stimulating hormone receptor) (1.20%), BLM (BLM RecQ like helicase) (0.62%), BRCA2 (BRCA2 DNA repair associated) (0.62%), and ATM (ATM serine/threonine kinase) (0.45%) were the top five genes with the highest overall prevalence. The top mutated pathways were all involved in DNA damage repair (DDR). Case–control analysis showed SBDS c.184A>T(p.K62*), TSHR c.1574T>C(p.F525S), BRIP1 (BRCA1 interacting helicase 1) c.1018C>T(p.L340F), and MUTYH (mutY DNA glycosylase) c.55C>T(p.R19*) were significantly associated with increased lung cancer risk (q value < 0.05). P/LP variants in certain genes were associated with early onset of lung cancer. Our study indicates that Chinese lung cancer patients have a higher prevalence of P/LP variants than previously reported. P/LP variants are distributed in multiple pathways and dominated by DNA damage repair‐associated pathways. The association between identified P/LP variants and lung cancer risk requires further studies for verification. [ABSTRACT FROM AUTHOR]

In cancer genomics, variant calling has advanced, but traditional mean accuracy evaluations are inadequate for biomarkers like tumor mutation burden, which vary significantly across samples, affecting immunotherapy patient selection and threshold settings. In this study, we introduce TMBstable, an innovative method that dynamically selects optimal variant calling strategies for specific genomic regions using a meta-learning framework, distinguishing it from traditional callers with uniform sample-wide strategies. The process begins with segmenting the sample into windows and extracting meta-features for clustering, followed by using a pre-trained meta-model to select suitable algorithms for each cluster, thereby addressing strategy-sample mismatches, reducing performance fluctuations and ensuring consistent performance across various samples. We evaluated TMBstable using both simulated and real non-small cell lung cancer and nasopharyngeal carcinoma samples, comparing it with advanced callers. The assessment, focusing on stability measures, such as the variance and coefficient of variation in false positive rate, false negative rate, precision and recall, involved 300 simulated and 106 real tumor samples. Benchmark results showed TMBstable's superior stability with the lowest variance and coefficient of variation across performance metrics, highlighting its effectiveness in analyzing the counting-based biomarker. The TMBstable algorithm can be accessed at https://github.com/hello-json/TMBstable for academic usage only. [ABSTRACT FROM AUTHOR]

The connectivity of the urban public transport network and the convenience of transfers between modes of transit are important factors that affect whether passengers choose public transport. Identifying the key nodes that affect network connectivity, direct access, transfers, and clarifying the main factors that restrict the network efficiency play important roles in improving the efficiency of the public transport network and establishing a "green city". On this premise, this paper constructs two single-layer networks and a composite network that can reflect the transfer relationship between 'bus–bus', 'metro–metro', and 'metro–bus' based on the method of Space-P. The composite network realizes the integration study of homogeneous and heterogeneous stops, lines, and transfer relationships in the public transport network. At the same time, five kinds of centrality indexes are applied to the transport transfer network, and the significance of these indexes in the network is explained. Through the comprehensive analysis of these five types of indexes, the key nodes affecting the network connectivity, direct access and transfer efficiency, can be identified more accurately. Taking the public transport network of Xi'an as an example, the structural characteristics of the networks, including scale-free and small-world characteristics, were empirically analyzed. The main stops that play important roles in networks were identified based on the integrated centrality, degrees, and weight degrees. The research results showed the following: (1) Xi'an's metro network, bus network, and metro–bus composite network all have scale-free and small-world characteristics. (2) The influence of the key stops of the metro network is concentrated, while the influence of the key stops of the bus network is scattered. (3) The public transport network in the first ring road area of Xi'an has the highest degree of direct access, and the core areas of the south, west, and north of Xi'an also have high direct access. However, the direct access in the area east of Xi'an is slightly lower. (4) Xi'an's bus transport network covers a large area, showing the characteristics of a dual-core "central + southern" network. (5) The metro–bus composite network demonstrates a closer connection between stops and a more balanced network. (6) Finally, the degree of direct access to stops in the bus transport network and metro transport network shows the characteristics of "the single core is dominant, and the circle diffusion weakens step by step". [ABSTRACT FROM AUTHOR]

The status of surrounding rocks dramatically influences the safety of construction workers, so the quality assessment of surrounding rocks has great significance. The uniaxial saturated compressive strength of rock (X1), the quality index of surrounding rock (X2), the frictional coefficient of the structural surface (X3), the joint spacing (X4), the state of groundwater(X5), and the integrity coefficient (X6) are selected as the initial evaluation index. Then, the game theory combination weighting-normal cloud model is introduced. Second, the certainty degree matrix of each index is established, and the weight coefficients of assessment indexes are determined based on the game theory combination weighting method. Finally, the quality level of surrounding rocks is judged. Compared with the traditional methods, the proposed model solves the fuzziness and randomness of different indexes, improves the reliability of the assessment process, and enhances the predictive accuracy of assessment results. In addition, it can provide a solution scheme for the evaluation indicators, which are difficult to quantify, and reduce the influence of human factors. The results obtained from the suggested model are consistent with the current specification. Its accuracy approaches 100%, and the method is feasible for the quality level assessment of surrounding rocks, providing a new technique and approach to assessing the risk level of surrounding rocks. [ABSTRACT FROM AUTHOR]