Elevation of H3K27me3 level contributes to the radioresistance of nasopharyngeal carcinoma by inhibiting OAS1 expression.

Radiotherapy has long been a main treatment option for nasopharyngeal carcinoma (NPC). However, during clinical treatment, NPC is prone to developing radioresistance, resulting in treatment failure. This study aims to examine the role of histone methylation in the induction of radioresistance. It was found that the radioresistance of NPC cells was related to the increase of the level of histone H3 lysine 27 trimethylation (H3K27me3). Treatment of cells with histone methyltransferase inhibitor GSK126 increased the radiosensitivity of NPC cells by triggering Bcl2 apoptosis regulator/BCL2-associated X, apoptosis regulator (Bcl2/BAX) signaling pathway. Bioinformatics analysis indicated that the expression of 2'-5'-oligoadenylate synthetase 1 (OAS1) was reduced in the radioresistant cells but increased in the GSK126-treated cells. Chromatin immunoprecipitation assay confirmed that the decrease of OAS1 expression in radioresistant cells was mainly due to the enrichment of H3K27me3 in its promoter region. Furthermore, downregulation of OAS1 reduced apoptosis due to the inhibition of Bcl2/BAX pathway after irradiation, while OAS1 overexpression increased radiosensitivity. Our findings revealed for the first time that the increase of H3K27me3 level was associated with the decrease of OAS1 expression, leading to the inhibition of apoptosis and ultimately contributing to the radioresistance of NPC cells. Moreover, the histone methyltransferase inhibitor GSK126 could overcome the radioresistance and thus might be a potential therapeutic strategy for NPC.NEW & NOTEWORTHY Our findings revealed for the first time that the increase of H3K27me3 level was associated with the decrease of OAS1 expression, leading to the inhibition of apoptosis and ultimately contributing to the radioresistance of NPC cells. Moreover, we demonstrated that the histone methyltransferase inhibitor GSK126 could be a promising therapeutic strategy for NPC by overcoming radioresistance, providing valuable insights into the clinical treatment of NPC.

Two-Dimensional Transition Metal Boride TMB12 (TM = V, Cr, Mn, and Fe) Monolayers: Robust Antiferromagnetic Semiconductors with Large Magnetic Anisotropy.

Currently, two-dimensional (2D) materials with intrinsic antiferromagnetism have stimulated research interest due to their insensitivity to external magnetic fields and absence of stray fields. Here, we predict a family of stable transition metal (TM) borides, TMB12 (TM = V, Cr, Mn, Fe) monolayers, by combining TM atoms and B12 icosahedra based on first-principles calculations. Our results show that the four TMB12 monolayers have stable antiferromagnetic (AFM) ground states with large magnetic anisotropic energy. Among them, three TMB12 (TM=V, Cr, Mn) monolayers display an in-plane easy magnetization axis, while the FeB12 monolayer has an out-of-plane easy magnetization axis. Among them, the CrB12 and the FeB12 monolayers are AFM semiconductors with band gaps of 0.13 eV and 0.35 eV, respectively. In particular, the AFM FeB12 monolayer is a spin-polarized AFM material with a Néel temperature of 125 K. Moreover, the electronic and magnetic properties of the CrB12 and the FeB12 monolayers can be modulated by imposing external biaxial strains. Our findings show that the TMB12 monolayers are candidates for designing 2D AFM materials, with potential applications in electronic devices.

Competing esterification and oligomerization reactions of typical long-chain alcohols to secondary organic aerosol formation.

Organosulfate (OSA) nanoparticles, as secondary organic aerosol (SOA) compositions, are ubiquitous in urban and rural environments. Hence, we systemically investigated the mechanisms and kinetics of aqueous-phase reactions of 1-butanol/1-decanol (BOL/DOL) and their roles in the formation of OSA nanoparticles by using quantum chemical and kinetic calculations. The mechanism results show that the aqueous-phase reactions of BOL/DOL start from initial protonation at alcoholic OH-groups to form carbenium ions (CBs), which engage in the subsequent esterification or oligomerization reactions to form OSAs/organosulfites (OSIs) or dimers. The kinetic results reveal that dehydration to form CBs for BOL and DOL reaction systems is the rate-limiting step. Subsequently, about 18% of CBs occur via oligomerization to dimers, which are difficult to further oligomerize because all reactive sites are occupied. The rate constant of BOL reaction system is one order of magnitude larger than that of DOL reaction system, implying that relative short-chain alcohols are more prone to contribute OSAs/OSIs than long-chain alcohols. Our results reveal that typical long-chain alcohols contribute SOA formation via esterification rather than oligomerization because OSA/OSI produced by esterification engages in nanoparticle growth through enhancing hygroscopicity.

Assessing the role of mineral particles in the atmospheric photooxidation of typical carbonyl compound.

Mineral particles are ubiquitous in the atmosphere and exhibit an important effect on the photooxidation of volatile organic compounds (VOCs). However, the role of mineral particles in the photochemical oxidation mechanism of VOCs remains unclear. Hence, the photooxidation reactions of acrolein (ARL) with OH radical (OH) in the presence and absence of SiO2 were investigated by theoretical approach. The gas-phase reaction without SiO2 has two distinct pathways (H-abstraction and OH-addition pathways), and carbonyl-H-abstraction is the dominant pathway. In the presence of SiO2, the reaction mechanism is changed, i.e., the dominant pathway from carbonyl-H-abstraction to OH-addition to carbonyl C-atom. The energy barrier of OH-addition to carbonyl C-atom deceases 21.33 kcal/mol when SiO2 is added. Carbonyl H-atom of ARL is occupied by SiO2 via hydrogen bond, and carbonyl C-atom is activated by SiO2. Hence, the main product changes from H-abstraction product to OH-adduct in the presence of SiO2. The OH-adduct exhibits a thermodynamic feasibility to yield HO2 radical and carboxylic acid via the subsequent reactions with O2, with implications for O3 formation and surface acidity of mineral particles.

A simple method improving acoustic mode identification capability based on genetic algorithms.

This letter develops a simple approach of duct mode identification and reconstruction based on genetic algorithms, which can extend the azimuthal mode order range compared to the conventional method based on the (spatial) discrete Fourier transform. The underlying principle is reconstructing the dominant mode from the modal identification forward model through optimization by exploiting the sparsity of the mode amplitude vector. The performance is experimentally demonstrated for detections of one and two azimuthal modes under noisy conditions with nondominant modes. Overall, the proposed genetic-algorithm-based framework for solving acoustic inverse problems is beneficial to duct acoustic testing, particularly design evaluations of fan blades and acoustic liners for aeroengines.

Robust noise-aware algorithm for randomized neural network and its convergence properties.

The concept of randomized neural networks (RNNs), such as the random vector functional link network (RVFL) and extreme learning machine (ELM), is a widely accepted and efficient network method for constructing single-hidden layer feedforward networks (SLFNs). Due to its exceptional approximation capabilities, RNN is being extensively used in various fields. While the RNN concept has shown great promise, its performance can be unpredictable in imperfect conditions, such as weight noises and outliers. Thus, there is a need to develop more reliable and robust RNN algorithms. To address this issue, this paper proposes a new objective function that addresses the combined effect of weight noise and training data outliers for RVFL networks. Based on the half-quadratic optimization method, we then propose a novel algorithm, named noise-aware RNN (NARNN), to optimize the proposed objective function. The convergence of the NARNN is also theoretically validated. We also discuss the way to use the NARNN for ensemble deep RVFL (edRVFL) networks. Finally, we present an extension of the NARNN to concurrently address weight noise, stuck-at-fault, and outliers. The experimental results demonstrate that the proposed algorithm outperforms a number of state-of-the-art robust RNN algorithms.

SDC1-TGM2-FLOT1-BHMT complex determines radiosensitivity of glioblastoma by influencing the fusion of autophagosomes with lysosomes.

Rationale: Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults. Radiotherapy has long been an important treatment for GBM. Despite recent advances in tumor radiotherapy, the prognosis of GBM remains poor due to radioresistance. Autophagy has been reported as a basic factor to prolong the survival of tumor under radiation stress, but the molecular mechanism of how autophagy contributes to GBM radioresistance was still lacking. Methods: We established radioresistant GBM cells and identified their protein profiles by Tandem mass tag (TMT) quantitative proteomic analysis, then chose the radioresistant genes based on the TMT analysis of GBM cells and differentially expressed genes (DEGs) analysis of GEO database. Colony formation, flow cytometry, qPCR, western blotting, mRFP-GFP-LC3, transmission electron microscopy, immunofluorescence, and co-IP assays were conducted to investigate the regulation mechanisms among these new-found molecules. Results: Syndecan 1 (SDC1) and Transglutaminase 2 (TGM2) were both overexpressed in the radioresistant GBM cells and tissues, contributing to the dismal prognosis of radiotherapy. Mechanically, after irradiation, SDC1 carried TGM2 from cell membrane into cytoplasm, and transported to lysosomes by binding to flotillin 1 (FLOT1), then TGM2 recognized the betaine homocysteine methyltransferase (BHMT) on autophagosomes to coordinate the encounter between autophagosomes and lysosomes. Conclusions: The SDC1-TGM2-FLOT1-BHMT copolymer, a novel member of the protein complexes involved in the fusion of lysosomes and autophagosomes, maintained the autophagic flux in the irradiated tumor cells and ultimately enhanced radioresistance of GBM, which provides new insights of the molecular mechanism and therapeutic targets of radioresistant GBM.

How does Information Exposure Affect Public Attitudes Toward GMO in China? The mediating and moderating roles of Conspiracy Belief and Knowledge.

Background: In China, controversy about genetically modified organisms (GMO) is ongoing and some regard GMO as a "product of a conspiracy," which affects people's attitudes (PAs) toward GMO. Beliefs in conspiracy theories (BCT) are formed from the information that people are exposed to. Information exposure not only constructs a pseudo-environment for individuals to perceive the world, but also generates external stimuli for their mental states and attitudes. People's objective knowledge and self-assessed knowledge play an important moderating role in this process. Method: The study adopted the stimulus-organism-response (SOR) model, with conspiracy beliefs as mediating variables, to test the mechanism of the independent variable of information exposure on the dependent variable of PAs toward GMO. Objective knowledge and self-assessed knowledge were introduced as moderator variables to explore the different roles of knowledge. A survey of Chinese adults was conducted in February 2022, and partial least squares structural equation modeling (PLS-SEM) was employed to estimate the multi-construct relationships. Results: Information exposure was significantly and directly connected with PAs toward GMO. BCT also played a significant mediating role. Unofficial information exposure reinforced beliefs in conspiracy theories. Stronger beliefs in conspiracy theories reduced people's willingness to consume GMO foods and made them pessimistic about the development prospects of GMO foods. In contrast, exposure to official information weakened people's beliefs in conspiracy theories and increased their willingness to consume GMO foods. In addition, the level of knowledge had a moderating role. Individual's objective knowledge can effectively reduce the negative relationship of conspiracy beliefs on attitudes toward GMO development. Conversely, individual's self-assessed knowledge can enhance the negative relationship of conspiracy beliefs on attitudes toward GMO development. Conclusion: Based on psychological and cognitive dimensions, this study provides a new perspective on how information exposure and people's attitudes toward GMO are related to each other and enriches the variable measurement dimension of knowledge. Simultaneously, it provides a localized explanation of the factors affecting people's attitudes toward GMO in China, providing a new theoretical basis for the subsequent development strategy of GMO foods.