Multi-Head Attention Mechanism Learning for Cancer New Subtypes and Treatment Based on Cancer Multi-Omics Data

Due to the high heterogeneity and clinical characteristics of cancer, there are significant differences in multi-omics data and clinical features among subtypes of different cancers. Therefore, the identification and discovery of cancer subtypes are crucial for the diagnosis, treatment, and prognosis of cancer. In this study, we proposed a generalization framework based on attention mechanisms for unsupervised contrastive learning (AMUCL) to analyze cancer multi-omics data for the identification and characterization of cancer subtypes. AMUCL framework includes a unsupervised multi-head attention mechanism, which deeply extracts multi-omics data features. Importantly, a decoupled contrastive learning model (DMACL) based on a multi-head attention mechanism is proposed to learn multi-omics data features and clusters and identify new cancer subtypes. This unsupervised contrastive learning method clusters subtypes by calculating the similarity between samples in the feature space and sample space of multi-omics data. Compared to 11 other deep learning models, the DMACL model achieved a C-index of 0.002, a Silhouette score of 0.801, and a Davies Bouldin Score of 0.38 on a single-cell multi-omics dataset. On a cancer multi-omics dataset, the DMACL model obtained a C-index of 0.016, a Silhouette score of 0.688, and a Davies Bouldin Score of 0.46, and obtained the most reliable cancer subtype clustering results for each type of cancer. Finally, we used the DMACL model in the AMUCL framework to reveal six cancer subtypes of AML. By analyzing the GO functional enrichment, subtype-specific biological functions, and GSEA of AML, we further enhanced the interpretability of cancer subtype analysis based on the generalizable AMUCL framework

Rescue of DNA damage after constricted migration reveals a mechano-regulated threshold for cell cycle.

Migration through 3D constrictions can cause nuclear rupture and mislocalization of nuclear proteins, but damage to DNA remains uncertain, as does any effect on cell cycle. Here, myosin II inhibition rescues rupture and partially rescues the DNA damage marker γH2AX, but an apparent block in cell cycle appears unaffected. Co-overexpression of multiple DNA repair factors or antioxidant inhibition of break formation also exert partial effects, independently of rupture. Combined treatments completely rescue cell cycle suppression by DNA damage, revealing a sigmoidal dependence of cell cycle on excess DNA damage. Migration through custom-etched pores yields the same damage threshold, with ∼4-µm pores causing intermediate levels of both damage and cell cycle suppression. High curvature imposed rapidly by pores or probes or else by small micronuclei consistently associates nuclear rupture with dilution of stiff lamin-B filaments, loss of repair factors, and entry from cytoplasm of chromatin-binding cGAS (cyclic GMP-AMP synthase). The cell cycle block caused by constricted migration is nonetheless reversible, with a potential for DNA misrepair and genome variation

Nuclear rupture at sites of high curvature compromises retention of DNA repair factors.

The nucleus is physically linked to the cytoskeleton, adhesions, and extracellular matrix-all of which sustain forces, but their relationships to DNA damage are obscure. We show that nuclear rupture with cytoplasmic mislocalization of multiple DNA repair factors correlates with high nuclear curvature imposed by an external probe or by cell attachment to either aligned collagen fibers or stiff matrix. Mislocalization is greatly enhanced by lamin A depletion, requires hours for nuclear reentry, and correlates with an increase in pan-nucleoplasmic foci of the DNA damage marker γH2AX. Excess DNA damage is rescued in ruptured nuclei by cooverexpression of multiple DNA repair factors as well as by soft matrix or inhibition of actomyosin tension. Increased contractility has the opposite effect, and stiff tumors with low lamin A indeed exhibit increased nuclear curvature, more frequent nuclear rupture, and excess DNA damage. Additional stresses likely play a role, but the data suggest high curvature promotes nuclear rupture, which compromises retention of DNA repair factors and favors sustained damage

Microfluidic Synthesis of the Tumor Microenvironment-Responsive Nanosystem for Type-I Photodynamic Therapy

Type I photosensitizers with aggregation-induced emission luminogens (AIE-gens) have the ability to generate high levels of reactive oxygen species (ROS), which have a good application prospect in cancer photodynamic therapy (PDT). However, the encapsulation and delivery of AIE molecules are unsatisfactory and seriously affect the efficiency of a practical therapy. Faced with this issue, we synthesized the metal-organic framework (MOF) in one step using the microfluidic integration technology and encapsulated TBP-2 (an AIE molecule) into the MOF to obtain the composite nanomaterial ZT. Material characterization showed that the prepared ZT had stable physical and chemical properties and controllable size and morphology. After being endocytosed by tumor cells, ZT was degraded in response to the acidic tumor microenvironment (TME), and then TBP-2 molecules were released. After stimulation by low-power white light, a large amount of •OH and H2O2 was generated by TBP-2 through type I PDT, thereby achieving a tumor-killing effect. Further in vitro cell experiments showed good biocompatibility of the prepared ZT. To the best of our knowledge, this report is the first on the microfluidic synthesis of multifunctional MOF for type I PDT in response to the TME. Overall, the preparation of ZT by the microfluidic synthesis method provides new insight into cancer therapy

Assessment of student knowledge integration in learning work and mechanical energy

Work and mechanical energy is a fundamental topic in introductory physics. Studies in existing literature have shown that students have difficulties in understanding work and mechanical energy, particularly the topic of work-energy theorem. To study students’ knowledge integration in learning work and mechanical energy, a conceptual framework model of work and mechanical energy was developed and applied to guide the design of an assessment for measuring students’ level of knowledge integration. Using the assessment, qualitative and quantitative data were collected in two high schools in an eastern Chinese city. The results reveal that the conceptual framework model can effectively represent the students’ knowledge structures at different levels of knowledge integration. In addition, the assessment is shown effective in identifying unique features of knowledge integration, including context dependence and fragmentation of knowledge components, memorization-based problem-solving strategies, and lack of meaningful connections between work and change in kinetic energy. The conceptual framework of work and mechanical energy and assessment results can provide useful information to facilitate instructional designs to promote knowledge integration

Corrosion behavior and cellular automata simulation of carbon steel in salt-spray environment

Abstract Scanning electron microscope (SEM) and X-ray diffraction (XRD) were used to discuss the corrosion loss and morphology of the pit and rust layer of carbon steel. It was found that the corrosion process is largely influenced by the cyclic shedding of surface corrosion products, in addition to being controlled by the mechanism of oxide film shedding and pit evolution. A corrosion mechanism (the mechanism of rust layer shedding) is proposed. As a result, in this paper, the corrosion process of the test steel is simulated by the cellular automata. It was set up that the mechanism of oxide film shedding, the mechanism of pit evolution, and the mechanism of rust layer shedding in Cellular Automata Simulation. The optimal time ratio and simulation parameters were found, and a predictable cellular automata corrosion simulation model was built, providing a solution for carbon steel’s service life prediction

DataSheet1_Aryl acrylonitriles synthesis enabled by palladium-catalyzed α-alkenylation of arylacetonitriles with vinyl halides/triflates.pdf

Aryl acrylonitriles are an important subclass of acrylonitriles in the medicinal chemistry and pharmaceutical industry. Herein, an efficient synthesis of aryl acrylonitrile derivatives using a Palladium/NIXANTPHOS-based catalyst system was developed. This approach furnishes a variety of substituted and functionalized aryl acrylonitriles (up to 95% yield). The scalability of the transformation and the synthetic versatility of aryl acrylonitrile were demonstrated.</p