Multi-layered computational gene networks by engineered tristate logics.

So far, biocomputation strictly follows traditional design principles of digital electronics, which could reach their limits when assembling gene circuits of higher complexity. Here, by creating genetic variants of tristate buffers instead of using conventional logic gates as basic signal processing units, we introduce a tristate-based logic synthesis (TriLoS) framework for resource-efficient design of multi-layered gene networks capable of performing complex Boolean calculus within single-cell populations. This sets the stage for simple, modular, and low-interference mapping of various arithmetic logics of interest and an effectively enlarged engineering space within single cells. We not only construct computational gene networks running full adder and full subtractor operations at a cellular level but also describe a treatment paradigm building on programmable cell-based therapeutics, allowing for adjustable and disease-specific drug secretion logics in vivo. This work could foster the evolution of modern biocomputers to progress toward unexplored applications in precision medicine.

Bulk-disclination correspondence in topological crystalline insulators.

Most natural and artificial materials have crystalline structures from which abundant topological phases emerge1-6. However, the bulk-edge correspondence-which has been widely used in experiments to determine the band topology from edge properties-is inadequate in discerning various topological crystalline phases7-16, leading to challenges in the experimental classification of the large family of topological crystalline materials4-6. It has been theoretically predicted that disclinations-ubiquitous crystallographic defects-can provide an effective probe of crystalline topology beyond edges17-19, but this has not yet been confirmed in experiments. Here we report an experimental demonstration of bulk-disclination correspondence, which manifests as fractional spectral charge and robust bound states at the disclinations. The fractional disclination charge originates from the symmetry-protected bulk charge patterns-a fundamental property of many topological crystalline insulators (TCIs). Furthermore, the robust bound states at disclinations emerge as a secondary, but directly observable, property of TCIs. Using reconfigurable photonic crystals as photonic TCIs with higher-order topology, we observe these hallmark features via pump-probe and near-field detection measurements. It is shown that both the fractional charge and the localized states emerge at the disclination in the TCI phase but vanish in the trivial phase. This experimental demonstration of bulk-disclination correspondence reveals a fundamental phenomenon and a paradigm for exploring topological materials.

Tunable liquid-solid hybrid thermal metamaterials with a topology transition.

Thermal metamaterials provide rich control of heat transport which is becoming the foundation of cutting-edge applications ranging from chip cooling to biomedical. However, due to the fundamental laws of physics, the manipulation of heat is much more constrained in conventional thermal metamaterials where effective heat conduction with Onsager reciprocity dominates. Here, through the inclusion of thermal convection and breaking the Onsager reciprocity, we unveil a regime in thermal metamaterials and transformation thermotics that goes beyond effective heat conduction. By designing a liquid-solid hybrid thermal metamaterial, we demonstrate a continuous switch from thermal cloaking to thermal concentration in one device with external tuning. Underlying such a switch is a topology transition in the virtual space of the thermotic transformation which is achieved by tuning the liquid flow via external control. These findings illustrate the extraordinary heat transport in complex multicomponent thermal metamaterials and pave the way toward an unprecedented regime of heat manipulation.

Machine Learning Methods for Small Data Challenges in Molecular Science.

Small data are often used in scientific and engineering research due to the presence of various constraints, such as time, cost, ethics, privacy, security, and technical limitations in data acquisition. However, big data have been the focus for the past decade, small data and their challenges have received little attention, even though they are technically more severe in machine learning (ML) and deep learning (DL) studies. Overall, the small data challenge is often compounded by issues, such as data diversity, imputation, noise, imbalance, and high-dimensionality. Fortunately, the current big data era is characterized by technological breakthroughs in ML, DL, and artificial intelligence (AI), which enable data-driven scientific discovery, and many advanced ML and DL technologies developed for big data have inadvertently provided solutions for small data problems. As a result, significant progress has been made in ML and DL for small data challenges in the past decade. In this review, we summarize and analyze several emerging potential solutions to small data challenges in molecular science, including chemical and biological sciences. We review both basic machine learning algorithms, such as linear regression, logistic regression (LR), k-nearest neighbor (KNN), support vector machine (SVM), kernel learning (KL), random forest (RF), and gradient boosting trees (GBT), and more advanced techniques, including artificial neural network (ANN), convolutional neural network (CNN), U-Net, graph neural network (GNN), Generative Adversarial Network (GAN), long short-term memory (LSTM), autoencoder, transformer, transfer learning, active learning, graph-based semi-supervised learning, combining deep learning with traditional machine learning, and physical model-based data augmentation. We also briefly discuss the latest advances in these methods. Finally, we conclude the survey with a discussion of promising trends in small data challenges in molecular science.

Transmembrane Graphene as an Electron Tunnel to Regulate the Intracellular Redox State.

Cellular redox homeostasis is essential for maintaining cellular activities, such as DNA synthesis and gene expression. Inspired by this, new therapeutic interventions have been rapidly developed to modulate the intracellular redox state using artificial transmembrane electron transport. However, current approaches that rely on external electric field polarization can disrupt cellular functions, limiting their in vivo application. Therefore, it is crucial to develop novel electric-field-free modulation methods. In this work, we for the first time found that graphene could spontaneously insert into living cell membranes and serve as an electron tunnel to regulate intracellular reactive oxygen species and NADH based on the spontaneous bipolar electrochemical reaction mechanism. This work provides a wireless and electric-field-free approach to regulating cellular redox states directly and offers possibilities for biological applications such as cell process intervention and treatment for neurodegenerative diseases.

Fibroblast growth factor 2 enhances BMSC stemness through ITGA2-dependent PI3K/AKT pathway activation.

Bone marrow-derived mesenchymal stem cells (BMSC) are promising cellular reservoirs for treating degenerative diseases, tissue injuries, and immune system disorders. However, the stemness of BMSCs tends to decrease during in vitro cultivation, thereby restricting their efficacy in clinical applications. Consequently, investigating strategies that bolster the preservation of BMSC stemness and maximize therapeutic potential is necessary. Transcriptomic and single-cell sequencing methodologies were used to perform a comprehensive examination of BMSCs with the objective of substantiating the pivotal involvement of fibroblast growth factor 2 (FGF2) and integrin alpha 2 (ITGA2) in stemness regulation. To investigate the impact of these genes on the BMSC stemness in vitro, experimental approaches involving loss and gain of function were implemented. These approaches encompassed the modulation of FGF2 and ITGA2 expression levels via small interfering RNA and overexpression plasmids. Furthermore, we examined their influence on the proliferation and differentiation capacities of BMSCs, along with the expression of stemness markers, including octamer-binding transcription factor 4, Nanog homeobox, and sex determining region Y-box 2. Transcriptomic analyzes successfully identified FGF2 and ITGA2 as pivotal genes responsible for regulating the stemness of BMSCs. Subsequent single-cell sequencing revealed that elevated FGF2 and ITGA2 expression levels within specific stem cell subpopulations are closely associated with stemness maintenance. Moreover, additional in vitro experiments have convincingly demonstrated that FGF2 effectively enhances the BMSC stemness by upregulating ITGA2 expression, a process mediated by the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. This conclusion was supported by the observed upregulation of stemness markers following the induction of FGF2 and ITGA2. Moreover, administration of the BEZ235 pathway inhibitor resulted in the repression of stemness transcription factors, suggesting the substantial involvement of the PI3K/AKT pathway in stemness preservation facilitated by FGF2 and ITGA2. This study elucidates the involvement of FGF2 in augmenting BMSC stemness by modulating ITGA2 and activating the PI3K/AKT pathway. These findings offer valuable contributions to stem cell biology and emphasize the potential of manipulating FGF2 and ITGA2 to optimize BMSCs for therapeutic purposes.

Transcriptome exploration of ferroptosis-related genes in TGFß- induced lens epithelial to mesenchymal transition during posterior capsular opacification development.

BACKGROUND: Posterior capsular opacification (PCO) is the main reason affecting the long-term postoperative result of cataract patient, and it is well accepted that fibrotic PCO is driven by transforming growth factor beta (TGFß) signaling. Ferroptosis, closely related to various ocular diseases, but has not been explored in PCO. METHODS: RNA sequencing (RNA-seq) was performed on both TGF-ß2 treated and untreated primary lens epithelial cells (pLECs). Differentially expressed genes (DEGs) associated with ferroptosis were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) to investigate their biological function. Additionally, protein-to-protein interactions among selected ferroptosis-related genes by PPI network and the top 10 genes with the highest score (MCC algorithm) were selected as the hub genes. The top 20 genes with significant fold change values were validated using quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Our analysis revealed 1253 DEGs between TGF-ß2 treated and untreated pLECs, uncovering 38 ferroptosis-related genes between two groups. Among these 38 ferroptosis-related genes,the most prominent GO enrichment analysis process involved in the response to oxidative stress (BPs), apical part of cell (CCs),antioxidant activity (MFs). KEGG were mainly concentrated in fluid shear stress and atherosclerosis, IL-17 and TNF signaling pathways, and validation of top 20 genes with significant fold change value were consistent with RNA-seq. CONCLUSIONS: Our RNA-Seq data identified 38 ferroptosis-related genes in TGF-ß2 treated and untreated pLECs, which is the first observation of ferroptosis related genes in primary human lens epithelial cells under TGF-ß2 stimulation.

Evidence of Spontaneous Formation of Two-Dimensional Amorphous Clathrates on Superhydrophilic Surfaces.

Clathrate hydrates reserved in the seabed are often dispersed in the pores of coarse-grained sediments; hence, their formation typically occurs under nanoconfinement. Herein, we show the first molecular dynamics (MD) simulation evidence of the spontaneous formation of two-dimensional (2D) clathrate hydrates on crystal surfaces without conventional nanoconfinement. The kinetic process of 2D clathrate formation is illustrated via simulated single-molecule deposition. 2D amorphous patterns are observed on various superhydrophilic face-centered cubic surfaces. Notably, the formation of 2D amorphous clathrate can occur over a wide range of temperatures, even at room temperature. The strong water-surface interaction, the characteristic properties of guest-gas molecules, and the underlying surface structure dictate the formation of 2D amorphous clathrates. Semiquantitative phase diagrams of 2D clathrates are constructed where representative patterns of 2D clathrates for characteristic gas molecules on prototypical Pd(111) and Pt(111) surfaces are confirmed by independent MD simulations. A tunable pattern of 2D amorphous clathrates is demonstrated by changing the lattice strain of the underlying substrate. Moreover, ab initio MD simulations confirm the stability of 2D amorphous clathrate. The underlining physical mechanism for 2D clathrate formation on superhydrophilic surfaces is elucidated, which offers deeper insight into the crucial role of water-surface interaction.

G-Quadruplex mRNAs Silencing with Inducible Ribonuclease Targeting Chimera for Precision Tumor Therapy.

Ribonuclease targeting chimera (RIBOTAC) represents an emerging strategy for targeted therapy. However, RIBOTAC that is selectively activated by bio-orthogonal or cell-specific triggers has not been explored. We developed a strategy of inducible RIBOTAC (iRIBOTAC) that enables on-demand degradation of G-quadruplex (G4) RNAs for precision cancer therapy. iRIBOTAC is designed by coupling an RNA G4 binder with a caged ribonuclease recruiter, which can be decaged by a bio-orthogonal reaction, tumor-specific enzyme, or metabolite. A bivalent G4 binder is engineered by conjugating a near-infrared (NIR) fluorescence G4 ligand to a noncompetitive G4 ligand, conferring fluorescence activation on binding G4s with synergistically enhanced affinity. iRIBOTAC is demonstrated to greatly knockdown G4 RNAs upon activation under bio-orthogonal or cell-specific stimulus, with dysregulation of gene expressions involving cell killing, channel regulator activity, and metabolism as revealed by RNA sequencing. This strategy also shows a crucial effect on cell fate with remarkable biochemical hallmarks of apoptosis. Mice model studies demonstrate that iRIBOTAC allows selective imaging and growth suppression of tumors with bio-orthogonal and tumor-specific controls, highlighting G4 RNA targeting and inducible silencing as a valuable RIBOTAC paradigm for cancer therapy.

Superdiffusive Rotation of Interfacial Water on Noble Metal Surface.

Interfacial water on a metal surface acts as an active layer through the reorientation of water, thereby facilitating the energy transfer and chemical reaction across the metal surface in various physicochemical and industrial processes. However, how this active interfacial water collectively behaves on flat noble metal substrates remains largely unknown due to the experimental limitation in capturing librational vibrational motion of interfacial water and prohibitive computational costs at the first-principles level. Herein, by implementing a machine-learning approach to train neural network potentials, we enable performing advanced molecular dynamics simulations with ab initio accuracy at a nanosecond scale to map the distinct rotational motion of water molecules on a metal surface at room temperature. The vibrational density of states of the interfacial water with two-layer profiles reveals that the rotation and vibration of water within the strong adsorption layer on the metal surface behave as if the water molecules in the bulk ice, wherein the O-H stretching frequency is well consistent with the experimental results. Unexpectedly, the water molecules within the adjacent weak adsorption layer exhibit superdiffusive rotation, contrary to the conventional diffusive rotation of bulk water, while the vibrational motion maintains the characteristic of bulk water. The mechanism underlying this abnormal superdiffusive rotation is attributed to the translation-rotation decoupling of water, in which the translation is restrained by the strong hydrogen bonding within the bilayer interfacial water, whereas the rotation is accelerated freely by the asymmetric water environment. This superdiffusive rotation dynamics may elucidate the experimentally observed large fluctuation of the potential of zero charge on Pt and thereby the conventional Helmholtz layer model revised by including the contribution of interfacial water orientation. The surprising superdiffusive rotation of vicinal water next to noble metals will shed new light on the physicochemical processes and the activity of water molecules near metal electrodes or catalysts.

Genetic fusion of CCL11 to antigens enhances antigenicity in nucleic acid vaccines and eradicates tumor mass through optimizing T-cell response.

Nucleic acid vaccines have shown promising potency and efficacy for cancer treatment with robust and specific T-cell responses. Improving the immunogenicity of delivered antigens helps to extend therapeutic efficacy and reduce dose-dependent toxicity. Here, we systematically evaluated chemokine-fused HPV16 E6/E7 antigen to improve the cellular and humoral immune responses induced by nucleotide vaccines in vivo. We found that fusion with different chemokines shifted the nature of the immune response against the antigens. Although a number of chemokines were able to amplify specific CD8 + T-cell or humoral response alone or simultaneously. CCL11 was identified as the most potent chemokine in improving immunogenicity, promoting specific CD8 + T-cell stemness and generating tumor rejection. Fusing CCL11 with E6/E7 antigen as a therapeutic DNA vaccine significantly improved treatment effectiveness and caused eradication of established large tumors in 92% tumor-bearing mice (n = 25). Fusion antigens with CCL11 expanded the TCR diversity of specific T cells and induced the infiltration of activated specific T cells, neutrophils, macrophages and dendritic cells (DCs) into the tumor, which created a comprehensive immune microenvironment lethal to tumor. Combination of the DNA vaccine with anti-CTLA4 treatment further enhanced the therapeutic effect. In addition, CCL11 could also be used for mRNA vaccine design. To summarize, CCL11 might be a potent T cell enhancer against cancer.

Chemically Inducible DNAzyme Sensor for Controllable Imaging of Metal Ions.

RNA-cleaving DNAzymes have emerged as a promising tool for metal ion detection. Achieving spatiotemporal control over their catalytic activity is essential for understanding the role of metal ions in various biological processes. While photochemical and endogenous stimuli-responsive approaches have shown potential for controlled metal ion imaging using DNAzymes, limitations such as photocytotoxicity, poor tissue penetration, or off-target activation have hindered their application for safe and precise detection of metal ions in vivo. We herein report a chemically inducible DNAzyme in which the catalytic core is modified to contain chemical caging groups at the selected backbone sites through systematic screening. This inducible DNAzyme exhibits minimal leakage of catalytic activity and can be reactivated by small molecule selenocysteines, which effectively remove the caging groups and restore the activity of DNAzyme. Benefiting from these findings, we designed a fluorogenic chemically inducible DNAzyme sensor for controlled imaging of metal ions with tunable activity and high selectivity in live cells and in vivo. This chemically inducible DNAzyme design expands the toolbox for controlling DNAzyme activity and can be easily adapted to detect other metal ions in vivo by changing the DNAzyme module, offering opportunities for precise biomedical diagnosis.

Unveiling the Structural Origins of Dynamic Diversity in Pd-Based Metallic Glasses.

The ß-relaxation is one of the major dynamic behaviors in metallic glasses (MGs) and exhibits diverse features. Despite decades of efforts, the understanding of its structural origin and contribution to the overall dynamics of MG systems is still unclear. Here two palladium-based Pd─Cu─P and Pd─Ni─P MGs are reported with distinct different ß-relaxation behaviors and reveal the structural origins for the difference using the advanced X-ray photon correlation spectroscopy and absorption fine structure techniques together with the first-principles calculations. The pronounced ß-relaxation and fast atomic dynamics in the Pd─Cu─P MG mainly come from the strong mobility of Cu atoms and their locally favored structures. In contrast, the motion of Ni atoms is constrained by P atoms in the Pd─Ni─P MG, leading to the weakened ß-relaxation peak and sluggish dynamics. The correlation of atomic dynamics with microscopic structures provides a way to understand the structural origins of different dynamic behaviors as well as the nature of aging in disordered materials.

Orthogonal Control of Nucleic Acid Function via Chemical Caging-Decaging Strategies.

The ability to precisely control the function of nucleic acids plays an important role in biosensing and biomedicine. In recent years, novel strategies employing biological, physical, and chemical triggers have been developed to modulate the function of nucleic acids spatiotemporally. These approaches commonly involve the incorporation of stimuli-responsive groups onto nucleic acids to block their functions until triggers-induced decaging restore activity. These inventive strategies deepen our comprehension of nucleic acid molecules' dynamic behavior and provide new techniques for precise disease diagnosis and treatment. Focusing on the spatiotemporal regulation of nucleic acid molecules through the chemical caging-decaging strategy, we here present an overview of the innovative triggered control mechanisms and accentuate their implications across the fields of chemical biology, biomedicine, and biosensing.

A systematic two-sample and bidirectional MR process highlights a unidirectional genetic causal effect of allergic diseases on COVID-19 infection/severity.

BACKGROUND: Allergic diseases (ADs) such as asthma are presumed risk factors for COVID-19 infection. However, recent observational studies suggest that the assumed correlation contradicts each other. We therefore systematically investigated the genetic causal correlations between various ADs and COVID-19 infection/severity. METHODS: We performed a two-sample, bidirectional Mendelian randomization (MR) study for five types of ADs and the latest round of COVID-19 GWAS meta-analysis datasets (critically ill, hospitalized, and infection cases). We also further validated the significant causal correlations and elucidated the potential underlying molecular mechanisms. RESULTS: With the most suitable MR method, asthma consistently demonstrated causal protective effects on critically ill and hospitalized COVID-19 cases (OR < 0.93, p < 2.01 × 10-2), which were further confirmed by another validated GWAS dataset (OR < 0.92, p < 4.22 × 10-3). In addition, our MR analyses also observed significant causal correlations of food allergies such as shrimp allergy with the risk of COVID-19 infection/severity. However, we did not find any significant causal effect of COVID-19 phenotypes on the risk of ADs. Regarding the underlying molecular mechanisms, not only multiple immune-related cells such as CD4+ T, CD8+ T and the ratio of CD4+/CD8+ T cells showed significant causal effects on COVID-19 phenotypes and various ADs, the hematology traits including monocytes were also significantly correlated with them. Conversely, various ADs such as asthma and shrimp allergy may be causally correlated with COVID-19 infection/severity by affecting multiple hematological traits and immune-related cells. CONCLUSIONS: Our systematic and bidirectional MR analyses suggest a unidirectional causal effect of various ADs, particularly of asthma on COVID-19 infection/severity, but the reverse is not true. The potential underlying molecular mechanisms of the causal effects call for more attention to clinical monitoring of hematological cells/traits and may be beneficial in developing effective therapeutic strategies for allergic patients following infection with COVID-19.

Bicyclol attenuates pulmonary fibrosis with silicosis via both canonical and non-canonical TGF-ß1 signaling pathways.

BACKGROUND: Silicosis is an irreversible fibrotic disease of the lung caused by chronic exposure to silica dust, which manifests as infiltration of inflammatory cells, excessive secretion of pro-inflammatory cytokines, and pulmonary diffuse fibrosis. As the disease progresses, lung function further deteriorates, leading to poorer quality of life of patients. Currently, few effective drugs are available for the treatment of silicosis. Bicyclol (BIC) is a compound widely employed to treat chronic viral hepatitis and drug-induced liver injury. While recent studies have demonstrated anti-fibrosis effects of BIC on multiple organs, including liver, lung, and kidney, its therapeutic benefit against silicosis remains unclear. In this study, we established a rat model of silicosis, with the aim of evaluating the potential therapeutic effects of BIC. METHODS: We constructed a silicotic rat model and administered BIC after injury. The FlexiVent instrument with a forced oscillation system was used to detect the pulmonary function of rats. HE and Masson staining were used to assess the effect of BIC on silica-induced rats. Macrophages-inflammatory model of RAW264.7 cells, fibroblast-myofibroblast transition (FMT) model of NIH-3T3 cells, and epithelial-mesenchymal transition (EMT) model of TC-1 cells were established in vitro. And the levels of inflammatory mediators and fibrosis-related proteins were evaluated in vivo and in vitro after BIC treatment by Western Blot analysis, RT-PCR, ELISA, and flow cytometry experiments. RESULTS: BIC significantly improved static compliance of lung and expiratory and inspiratory capacity of silica-induced rats. Moreover, BIC reduced number of inflammatory cells and cytokines as well as collagen deposition in lungs, leading to delayed fibrosis progression in the silicosis rat model. Further exploration of the underlying molecular mechanisms revealed that BIC suppressed the activation, polarization, and apoptosis of RAW264.7 macrophages induced by SiO2. Additionally, BIC inhibited SiO2-mediated secretion of the inflammatory cytokines IL-1ß, IL-6, TNF-α, and TGF-ß1 in macrophages. BIC inhibited FMT of NIH-3T3 as well as EMT of TC-1 in the in vitro silicosis model, resulting in reduced proliferation and migration capability of NIH-3T3 cells. Further investigation of the cytokines secreted by macrophages revealed suppression of both FMT and EMT by BIC through targeting of TGF-ß1. Notably, BIC blocked the activation of JAK2/STAT3 in NIH-3T3 cells required for FMT while preventing both phosphorylation and nuclear translocation of SMAD2/3 in TC-1 cells necessary for the EMT process. CONCLUSION: The collective data suggest that BIC prevents both FMT and EMT processes, in turn, reducing aberrant collagen deposition. Our findings demonstrate for the first time that BIC ameliorates inflammatory cytokine secretion, in particular, TGF-ß1, and consequently inhibits FMT and EMT via TGF-ß1 canonical and non-canonical pathways, ultimately resulting in reduction of aberrant collagen deposition and slower progression of silicosis, supporting its potential as a novel therapeutic agent.

Unsupervised underwater imaging based on polarization and binocular depth estimation.

Scattering caused by suspended particles in the water severely reduces the radiance of the scene. This paper proposes an unsupervised underwater restoration method based on binocular estimation and polarization. Based on the correlation between the underwater transmission process and depth, this method combines the depth information and polarization information in the scene, uses the neural network to perform global optimization and the depth information is recalculated and updated in the network during the optimization process, and reduces the error generated by using the polarization image to calculate parameters, so that detailed parts of the image are restored. Furthermore, the method reduces the requirement for rigorous pairing of data compared to previous approaches for underwater imaging using neural networks. Experimental results show that this method can effectively reduce the noise in the original image and effectively preserve the detailed information in the scene.

Integrated MRI radiomics, tumor microenvironment, and clinical risk factors for improving survival prediction in patients with glioblastomas.

PURPOSE: To construct a comprehensive model for predicting the prognosis of patients with glioblastoma (GB) using a radiomics method and integrating clinical risk factors, tumor microenvironment (TME), and imaging characteristics. MATERIALS AND METHODS: In this retrospective study, we included 148 patients (85 males and 63 females; median age 53 years) with isocitrate dehydrogenase-wildtype GB between January 2016 and April 2022. Patients were randomly divided into the training (n = 104) and test (n = 44) sets. The best feature combination related to GB overall survival (OS) was selected using LASSO Cox regression analyses. Clinical, radiomics, clinical-radiomics, clinical-TME, and clinical-radiomics-TME models were established. The models' concordance index (C-index) was evaluated. The survival curve was drawn using the Kaplan-Meier method, and the prognostic stratification ability of the model was tested. RESULTS: LASSO Cox analyses were used to screen the factors related to OS in patients with GB, including MGMT (hazard ratio [HR] = 0.642; 95% CI 0.414-0.997; P = 0.046), TERT (HR = 1.755; 95% CI 1.095-2.813; P = 0.019), peritumoral edema (HR = 1.013; 95% CI 0.999-1.027; P = 0.049), tumor purity (TP; HR = 0.982; 95% CI 0.964-1.000; P = 0.054), CD163 + tumor-associated macrophages (TAMs; HR = 1.049; 95% CI 1.021-1.078; P < 0.001), CD68 + TAMs (HR = 1.055; 95% CI 1.018-1.093; P = 0.004), and the six radiomics features. The clinical-radiomics-TME model had the best survival prediction ability, the C­index was 0.768 (0.717-0.819). The AUC of 1­, 2­, and 3­year OS prediction in the test set was 0.842, 0.844, and 0.795, respectively. CONCLUSION: The clinical-radiomics-TME model is the most effective for predicting the survival of patients with GB. Radiomics features, TP, and TAMs play important roles in the prognostic model.

Observation of Topological Transition in Floquet Non-Hermitian Skin Effects in Silicon Photonics.

Non-Hermitian physics has greatly enriched our understanding of nonequilibrium phenomena and uncovered novel effects such as the non-Hermitian skin effect (NHSE) that has profoundly revolutionized the field. NHSE has been predicted in systems with nonreciprocal couplings which, however, are challenging to realize in experiments. Without nonreciprocal couplings, the NHSE can also emerge in systems with coexisting gauge fields and loss or gain (e.g., in Floquet non-Hermitian systems). However, such Floquet NHSE remains largely unexplored in experiments. Here, we realize the Floquet NHSEs in periodically modulated optical waveguides integrated on a silicon photonic platform. By engineering the artificial gauge fields induced by the periodical modulation, we observe various Floquet NHSE phases and unveil their rich topological transitions. Remarkably, we discover the transitions between the unipolar NHSE phases and an unconventional bipolar NHSE phase, which is accompanied by the directional reversal of the NHSEs. The underlying physics is revealed by the band winding in complex quasienergy space which undergoes a topology change from isolated loops with the same winding to linked loops with opposite windings. Our work unfolds a new route toward Floquet NHSEs originating from the interplay between gauge fields and dissipation effects, and thus offers fundamentally new ways for steering light and other waves.

The involvement of keratinocytes in pruritus of chronic inflammatory dermatosis.

Frequent itching and incessant scratching are commonly observed in various chronic inflammatory skin conditions, including atopic dermatitis and psoriasis. The persistent and prolonged nature of pruritus can worsen one's quality of life. Keratinocytes (KCs), the predominant cells of the epidermis, have been confirmed to interact with sensory neurons and immune cells and be involved in chronic skin inflammatory diseases associated with pruritus. Initially, KCs and sensory neurons form a unique synapse-like connection within the epidermis, serving as the structural foundation for their interaction. Additionally, several receptors, including toll-like receptors and protease-activated receptor 2, expressed on KCs, become activated in an inflammatory milieu. On the one hand, activated KCs are sources of pro-inflammatory cytokines and neurotrophic factors, such as adenosine triphosphate, thymic stromal lymphopoietin, and nerve growth factor, which directly or indirectly participate in stimulating sensory neurons, thereby contributing to the itch sensations. On the other hand, KCs also function as primary transducers alongside intraepidermal nerve endings, directly initiating pruritic responses. This review summarizes the current literature and highlights the critical role of KCs in the development and persistence of chronic itch in inflammatory skin disorders.