Explore the vast range of titles available.

Long noncoding RNAs (lncRNAs) are emerging as a new class of important regulators of signal transduction in tissue homeostasis and cancer development. Liquid–liquid phase separation (LLPS) occurs in a wide range of biological processes, while its role in signal transduction remains largely undeciphered. In this study, we uncovered a lipid-associated lncRNA, small nucleolar RNA host gene 9 ( SNHG9 ) as a tumor-promoting lncRNA driving liquid droplet formation of Large Tumor Suppressor Kinase 1 (LATS1) and inhibiting the Hippo pathway. Mechanistically, SNHG9 and its associated phosphatidic acids (PA) interact with the C-terminal domain of LATS1, promoting LATS1 phase separation and inhibiting LATS1-mediated YAP phosphorylation. Loss of SNHG9 suppresses xenograft breast tumor growth. Clinically, expression of SNHG9 positively correlates with YAP activity and breast cancer progression. Taken together, our results uncover a novel regulatory role of a tumor-promoting lncRNA (i.e., SNHG9 ) in signal transduction and cancer development by facilitating the LLPS of a signaling kinase (i.e., LATS1).

Background Cyclosporin A (CsA) is a promising therapeutic drug for myocardial ischemia reperfusion injury (MI/RI) because of its definite inhibition to the opening of mitochondrial permeability transition pore (mPTP). However, the application of cyclosporin A to treat MI/RI is limited due to its immunosuppressive effect to other normal organ and tissues. SS31 represents a novel mitochondria-targeted peptide which can guide drug to accumulate into mitochondria. In this paper, mitochondria-targeted nanoparticles (CsA@PLGA-PEG-SS31) were prepared to precisely deliver cyclosporin A into mitochondria of ischemic cardiomyocytes to treat MI/RI. Results CsA@PLGA-PEG-SS31 was prepared by nanoprecipitation. CsA@PLGA-PEG-SS31 showed small particle size (~ 50 nm) and positive charge due to the modification of SS31 on the surface of nanoparticles. CsA@PLGA-PEG-SS31 was stable for more than 30 days and displayed a biphasic drug release pattern. The in vitro results showed that the intracellular uptake of CsA@PLGA-PEG-SS31 was significantly enhanced in hypoxia reoxygenation (H/R) injured H9c2 cells. CsA@PLGA-PEG-SS31 delivered CsA into mitochondria of H/R injured H9c2 cells and subsequently increased the viability of H/R injured H9c2 cell through inhibiting the opening of mPTP and production of reactive oxygen species. In vivo results showed that CsA@PLGA-PEG-SS31 accumulated in ischemic myocardium of MI/RI rat heart. Apoptosis of cardiomyocyte was alleviated in MI/RI rats treated with CsA@PLGA-PEG-SS31, which resulted in the myocardial salvage and improvement of cardiac function. Besides, CsA@PLGA-PEG-SS31 protected myocardium from damage by reducing the recruitment of inflammatory cells and maintaining the integrity of mitochondrial function in MI/RI rats. Conclusion CsA@PLGA-PEG-SS31 exhibited significant cardioprotective effects against MI/RI in rats hearts through protecting mitochondrial integrity, decreasing apoptosis of cardiomyocytes and myocardial infract area. Thus, CsA@PLGA-PEG-SS31 offered a promising therapeutic method for patients with acute myocardial infarction.

Using friction force microscopy, we compared the nanoscale frictional characteristics of atomically thin sheets of graphene, molybdenum disulfide (MoS₂), niobium diselenide, and hexagonal boron nitride exfoliated onto a weakly adherent substrate (silicon oxide) to those of their bulk counterparts. Measurements down to single atomic sheets revealed that friction monotonically increased as the number of layers decreased for all four materials. Suspended graphene membranes showed the same trend, but binding the graphene strongly to a mica surface suppressed the trend. Tip-sample adhesion forces were indistinguishable for all thicknesses and substrate arrangements. Both graphene and MoS₂ exhibited atomic lattice stick-slip friction, with the thinnest sheets possessing a sliding-length-dependent increase in static friction. These observations, coupled with finite element modeling, suggest that the trend arises from the thinner sheets' increased susceptibility to out-of-plane elastic deformation. The generality of the results indicates that this may be a universal characteristic of nanoscale friction for atomically thin materials weakly bound to substrates.

The surface defects on a shield subway tunnel can significantly affect the serviceability of the tunnel structure and may compromise operation safety. To effectively detect multiple surface defects, this study uses a tunnel inspection trolley (TIT) based on the mobile laser scanning technique. By conducting an inspection of the shield tunnel on a metro line section, various surface defects are identified with the TIT, including water leakage defects, dislocation, spalling, cross-section deformation, etc. To explore the root causes of the surface defects, association rules between different defects are calculated using an improved Apriori algorithm. The results show that: (i) there are significant differences in different association rules for various surface defects on the shield tunnel; (ii) the average confidence of the association rule “dislocation & spalling → water leakage” is as high as 57.78%, indicating that most of the water leakage defects are caused by dislocation and spalling of the shield tunnel in the sections being inspected; (iii) the weakest rule appears at “water leakage → spalling”, with an average confidence of 13%. The association analysis can be used for predicting the critical defects influencing structural reliability and operation safety, such as water leakage, and optimizing the construction and maintenance work for a shield subway tunnel.

Axially chiral heterobiaryl frameworks are privileged structures in many natural products, pharmaceutically active molecules, and chiral ligands. Therefore, a variety of approaches for constructing these skeletons have been developed. Among them, de novo synthesis, due to its highly convergent and superior atom economy, serves as a promising strategy to access these challenging scaffolds including C-N, C-C, and N-N chiral axes. So far, several elegant reviews on the synthesis of axially chiral heterobiaryl skeletons have been disclosed, however, atroposelective construction of the heterobiaryl subunits by de novo synthesis was rarely covered. Herein, we summarized the recent advances in the catalytic asymmetric synthesis of the axially chiral heterobiaryl scaffold via de novo synthetic strategies. The related mechanism, scope, and applications were also included.

Background PTH plays a crucial role in bone remodelling by regulating bone formation. Pre-collagen type 1 N-terminal peptide (P1NP) is a key biomarker indicative of new bone formation. However, the relationship between PTH levels and P1NP levels in patients with osteoporotic fractures (OPFs) has not been fully elucidated. Methods This study analyzed data from 588 OPFs patients hospitalized between January 2015 and March 2022. Serum P1NP concentration serve as the dependent variable, while PTH level serve as the exposure variable. Covariates included age, gender; Charlson comorbidity index (CCI), body mass index (BMI), lymphocyte, neutrophil, monocyte, low-density lipoprotein (LDL), platelet, triglyceride, albumin, hemoglobin. Generalized estimating equations were used to assess the independent association between PTH and P1NP levels, adjusting for covariates. Non-linear relationships were evaluated using generalized additive models. Results This study found a positive association between PTH level and P1NP level in patients with OPFs (β = 0.59; 95% CI [confident interval] = 0.22 to 0.96; P  = 0.0018). This association remained significant after multivariate adjustment. Moreover, the nonlinear model showed a threshold effect, with PTH level below 16.63 (pg/mL) being positively correlated with P1NP (β = 1.69; 95% CI = 0.90 to 2.47; P  < 0.0001). However, this correlation did not hold true for PTH level above 16.63 (pg/mL) (β = 0.37; 95% CI = -0.34 to 1.07; P  = 0.3091). Conclusion This study identified an inflection point and a nonlinear, threshold effect in the relationship between PTH and P1NP levels. Further research is needed to confirm these findings.

Background 3-Hydroxy butyrate dehydrogenase 2 (BDH2) is a short-chain dehydrogenase/reductase family member that plays a key role in the development and pathogenesis of human cancers. However, the role of BDH2 in gastric cancer (GC) remains largely unclear. Our study aimed to ascertain the regulatory mechanisms of BDH2 in GC, which could be used to develop new therapeutic strategies. Methods Western blotting, immunohistochemistry, and RT-PCR were used to investigate the expression of BDH2 in GC specimens and cell lines. Its correlation with the clinicopathological characteristics and prognosis of GC patients was analysed. Functional assays, such as CCK-8 and TUNEL assays, transmission electron microscopy, and an in vivo tumour growth assay, were performed to examine the proliferation, apoptosis, and autophagy of GC cells. Related molecular mechanisms were clarified by luciferase reporter, coimmunoprecipitation, and ubiquitination assays. Results BDH2 was markedly downregulated in GC tissues and cells, and the low expression of BDH2 was associated with poor survival of GC patients. Functionally, BDH2 overexpression significantly induced apoptosis and autophagy in vitro and in vivo. Mechanistically, BDH2 promoted Keap1 interaction with Nrf2 to increase the ubiquitination level of Nrf2. Ubiquitination/degradation of Nrf2 inhibited the activity of ARE to increase accumulation of reactive oxygen species (ROS), thereby inhibiting the phosphorylation levels of Akt Ser473 and mTOR Ser2448 . Conclusions Our study indicates that BDH2 is an important tumour suppressor in GC. BDH2 regulates intracellular ROS levels to mediate the PI3K/Akt/mTOR pathway through Keap1/Nrf2/ARE signalling, thereby inhibiting the growth of GC.

In this paper, we study the scenario in which the matter field is an electromagnetic field nonminimally coupled to the bumblebee vector field. We present exact charged spherically symmetric black hole solutions and slowly rotating charged solutions in bumblebee gravity with and without a cosmological constant. The static spherically symmetric solutions describe the Reissner–Nordström-like black hole and Reissner–Nordström-(anti) de Sitter-like black hole, while the stationary and axially symmetric solutions describe the Kerr–Newman-like black hole and Kerr–Newman–(anti) de Sitter-like black hole. We utilize the Hamilton–Jacobi formalism to study the shadows of the black holes. Additionally, we investigate the effect of the electric charge and Lorentz-violating parameters on the radius of the shadow reference circle and the distortion parameter. We find that the radius of the reference circle decreases with the Lorentz-violating parameter and the charge parameter, while the distortion parameter increases with the Lorentz-violating parameter and the charge parameter.

With the rapid development of online education, personalized learning path recommendations have played an increasingly important role in enhancing learning efficiency and optimizing learning experiences. However, existing learning path recommendation methods still face significant limitations in knowledge structure modeling, dynamic learner knowledge state perception, and recommendation strategy optimization. To address these challenges, this study proposes an online personalized English learning path recommendation method that integrates a domain knowledge graph with deep reinforcement learning. The graph encodes prerequisite (directed) and semantic (undirected) relations and uses a resource-to-knowledge mapping to structurally bind learning resources to concepts; learner mastery is updated in real time via interaction feedback, graph-based propagation, and an exponential forgetting mechanism. The task is formulated as an MDP in which Q-learning provides value-based pruning of prerequisite-feasible candidates and PPO selects the final action from the pruned set (a prune–then–select workflow). Deployed as a WeChat Mini Program, the system was evaluated on  200 active learners over three months with 18,742 valid interactions. It achieves Precision 0.85, Recall 0.82, F1 0.84, MAE 0.12, RMSE 0.18, cumulative return G 650, and AMG 0.42, consistently outperforming strong baselines AKT, LightGCN, TA-RL, cDQN, KG-H, MC, CF, and Rule; paired per-learner tests with BH–FDR control confirm significance, particularly for Top-K [3,10]. Engineering evaluations show an average  241 ms latency for personalized recommendation at 200 concurrent threads and sub-350 ms / sub-500 ms startup on Wi-Fi / 4G across mainstream devices, demonstrating practical scalability and real-time applicability.

N6-methyladenosine (m6A) modifications play an essential role in tumorigenesis. These modifications modulate RNAs, including mRNAs and lncRNAs. However, the prognostic role of m6A-related lncRNAs in head and neck squamous cell carcinoma (HNSCC) is poorly understood. Based on LASSO Cox regression, enrichment analysis, univariate and multivariate Cox regression analysis, a prognostic risk model, and consensus clustering analysis, we analyzed 12 m6A-related lncRNAs in HNSCC sample data from The Cancer Genome Atlas (TCGA) database. We found 12 m6A-related lncRNAs in the training cohort and validated them in all cohorts by Kaplan–Meier and Cox regression analyses, revealing their independent prognostic value in HNSCC. Moreover, ROC analysis was conducted, confirming the strong predictive ability of this signature for HNSCC survival. GSEA and detailed immune infiltration analyses revealed specific pathways associated with m6A-related lncRNAs. In this study, a novel risk model including twelve genes (SAP30L-AS1, AC022098.1, LINC01475, AC090587.2, AC008115.3, AC015911.3, AL122035.2, AC010226.1, AL513190.1, ZNF32-AS1, AL035587.1 and AL031716.1) was built. It could accurately predict HNSCC outcomes and could provide new therapeutic targets for HNSCC patients.