Westlake Health Center

Steelmaking slag contains valuable components. Its high phosphorus content hinders its reutilization in the steelmaking process. This study proposes an efficient phosphate removal process using molten CaCl2 as the reaction medium, aiming to enable slag recycling and P recovery. Experimental results show that nearly all P-bearing phases in steelmaking slag are leached into molten CaCl2 under the tested conditions (850 to 1000 °C, slag/CaCl2 mass ratios 1:10 to 1:2.5). The leaching mechanism involves the reaction of slag's P-bearing phases with CaCl2 to form intermediates (Ca2PO4Cl and Ca3SiO4Cl2), which dissociate into PO43– and other ions in the melt. For other elements: Si(IV) leaches continuously but incompletely; Fe(II) and Mn(II) concentrations in the melt first increase then decrease, attributed to the evaporation of volatile FeCl2 and MnCl2; Mg and Al remain nearly unleachable. After leaching, adding carbon to the P-enriched melt achieves complete P(V) removal via carbothermal reduction. This molten CaCl2-based approach provides a sustainable alternative to conventional technologies, offering valuable insights for the comprehensive utilization of P-bearing solid wastes.

Diffuse intrinsic pontine glioma (DIPG) is one of the most devastating childhood brain cancers, with a median survival of less than one year and almost no long-term survivors. Classified as a subtype of diffuse midline glioma (DMG) and characterized by the H3K27M mutation, DIPG remains resistant to surgery and conventional chemotherapy due to its location in the brainstem and its highly adaptive biology. ONC201, a first-in-class imipridone, has shown positive early clinical results in children with H3K27M-mutant DIPG by blocking dopamine receptor D2 (DRD2), overactivating the mitochondrial protease ClpP, and triggering stress and apoptosis pathways in tumor cells. While newer imipridones like ONC206 and ONC212 appear even more potent in laboratory models, ONC201 has the strongest clinical track record to date, making it the most practical candidate for exploring combination strategies.CRISPR-Cas9 gene editing could be used to boost ONC201’s effects by targeting the survival mechanisms DIPG cells rely on. Potential strategies include knocking out dopamine receptors like DRD2/3, shutting down integrated stress response regulators such as PERK and GCN2, and removing anti-apoptotic genes like BCL2L1, MCL1, and XIAP that block cell death. Other promising approaches include editing PDGFRA or AKT to weaken compensatory growth pathways, or targeting CLPX to intensify ONC201-induced mitochondrial collapse. These genetic edits could work together to prevent resistance, amplify stress signals, and push DIPG cells past the point of recovery.Still, major challenges remain. Delivering CRISPR safely across the blood–brain barrier is a significant hurdle, and most studies so far are limited to cell culture or glioblastoma models rather than DIPG itself. This highlights the urgent need for DIPG-specific in vivo research before clinical translation is possible. This review brings together what is currently known about ONC201, CRISPR, and their potential synergy, outlining both the opportunities and obstacles in moving toward a more effective treatment strategy for this lethal pediatric cancer.

Abstract Antibody-mediated cis-delivery and trans-delivery both direct cytokines to tumors and have been extensively investigated in clinical trials. However, a comparative analysis of their differential effects on cytokine activity is still lacking. In this study, we initially verify that cis-delivery of cytokine demonstrates a markedly stronger antitumor effect than trans-delivery, but it also exhibits certain drawbacks, including severe toxicity, insufficient activation of CD25 + CD8 + T cells, and enhanced stimulation of intratumoral regulatory T cells (Tregs). To further address these issues, we developed a conditionally releasable and cis-delivering IL-15 immunocytokine (termed PMIS), which can selectively release a free IL-15 superagonist within tumors rather than immobilizing IL-15 to PD-1 + Tregs, thereby potently stimulating CD25 + CD8 + T cells. Mice treated with PMIS showed significantly reduced systemic toxicities while achieving notably stronger antitumor effects. Administered either alone or in combination with other therapies, PMIS exhibits great potential for inhibiting orthotopic cold tumor and its metastases. Mechanistically, the significant activation of the pre-existing intratumoral CD25 + CD8 + T cells and the improved CD25 + CD8/Treg ratio contribute to the enhanced antitumor response of PMIS. These findings underscore the indispensable role of CD25 + CD8 + T cells in cis-delivering IL-15 and provide a promising strategy for overcoming resistance to therapies and effectively controlling advanced cold tumors.

The rapid growth of single-cell and spatial omics has outpaced computational methods capable of unifying these data into a cohesive framework for tissue atlas construction and cross-sample analysis. A critical bottleneck lies in the inability of existing tools to co-embed cells from diverse technologies-spanning transcriptomics, epigenomics, and proteomics-into a shared reference space while preserving spatial architecture and molecular specificity. Here, we present Garfield (Graph-based Contrastive Learning Enables Fast Single-Cell Embedding), a geometric deep-learning framework that addresses these challenges through spatially or molecularly aware cell embedding. Leveraging a graph contrastive learning framework, Garfield learns a shared embedding space for data generated by diverse technologies, enabling seamless construction and querying of spatial reference atlases. Our results show that Garfield consistently outperforms state-of-the-art benchmark models in identifying spatial niches across multiple datasets. We further demonstrate Garfield's versatility by applying it to multimodal spatial data, including gene expression and chromatin accessibility, where it successfully identifies distinct niches in the mouse brain. Notably, Garfield reveals tumor microenvironment heterogeneity in non-small cell lung cancer and breast cancer, uncovered conserved, barrier-like immune niches at tumor margins orchestrating CD80-mediated T cell-B cell-dendritic cell interactions and IFN-y/B cell activation pathways, forming spatially coordinated immune surveillance hubs. These findings underscore Garfield's potential to advance spatial omics research by offering a robust, scalable solution for integrating and interpreting complex spatial data across diverse tissue types and modalities.

Abstract Perturbations such as dietary shifts and drug treatment can reduce gut microbiome diversity, with negative health effects on the host, but predicting changes to community diversity is challenging due to the many mechanisms by which species interact. While both nutrient competition and cross-feeding can play major roles in microbiota assembly, the effect of environmental stresses such as antibiotics is typically studied experimentally in monoculture, and most theoretical studies have focused on communities that interact via nutrient competition alone. To investigate the interplay between nutrient competition, stresses that inhibit growth, and cross-feeding, we introduce a consumer-resource model that includes all three factors and captures a wide range of cross-feeding network architectures with a single parameter. For three-species communities, we found that coexistence during narrow-spectrum growth inhibition was maximal with a cyclic cross-feeding network, while fully connected cross-feeding networks maximized coexistence during broad-spectrum growth inhibition. However, the effects of cyclic cross-feeding were particularly sensitive to community size and the number of targeted species; for communities with more than six species and resources, cyclic cross-feeding can be detrimental to coexistence due to instability. Our findings highlight the complex effects of cross-feeding network architecture on coexistence when growth inhibition reshapes the nutrient competition landscape, with potential applications to microbial communities in all natural environments, where they are often exposed to agents such as drugs, temperature, and pH modulation.

Abstract Plants can generate structural diversity by enzymatic rearrangement of a central intermediate. 19E-geisssochizine is one such chemically versatile intermediate that plays a central role in the biosynthesis of monoterpene indole alkaloids such as strychnine, ibogaine and vinblastine. Here we report how 19E-geissoschizine undergoes oxidative transformations to generate four distinct alkaloid scaffolds through the action of three biosynthetic enzymes. Using in vitro enzymatic assays and gene silencing, we demonstrate how these three cytochrome P450 enzymes in the medicinal plantCatharanthus roseustransform 19E-geisssochzine intostrychnos, sarpagan, akuammiline-type, andmavacurane-type alkaloids. We use mutational analysis to show how minimal changes to the active site of these similar enzymes modulate product specificity. This work highlights how substrate reactivity and enzyme mutations work synergistically to generate chemical diversity.

Social psychologists have been unveiling the various psychological components to the optimal wellbeing of an individual. Arguably, optimism and happiness have been associated with proper interventions that lead to one’s health by pursuing mindfulness meditation and exercise, which have positively led to a well-supported cognition, brain, and neural functions. Researchers have also witnessed how exercise can also promote greater body image, by leading to positive minds and intrinsic motivation, which have led to rewiring the brain and neural circuits as well as functions in a positive manner. In the recent years, technological advancements have also made AI-devised personalized telemedicine more accessible, where in the space of mental health, patients are able to connect with therapists in a more accessible manner through the support of AI, prototypes and mental health platforms that have revolutionized the mental health industry.