Wound localization and housing conditions dictate repair dynamics and scar formation
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The decreasing housing utilization efficiency in China’s cities
‘Ghost cities’ are a well-known phenomenon of (almost) complete vacancy of urban living space in China. Underutilization of urban living space, however, is far more common than complete vacancy. Here we propose the concept of housing utilization efficiency (HUE) and present the following findings: (1) the overall HUE in China’s highly urbanized areas decreased from 84% in 2010 to 78% in 2020, (2) the HUE in central, old urban areas was generally lower than that in the outer layers of urban areas and declined more from 2010 to 2020 and (3) four development types are found to represent different patterns of urban population movement, urban housing growth and HUE change at the intraurban level. These findings provide comprehensive insight into the discrepancies between urban housing supply and demand in China and highlight their connections to the country’s particular urbanization characteristics and policies, which are crucial for future housing development and planning.
Urban inequality, the housing crisis and deteriorating water access in US cities
The housing unaffordability and cost-of-living crisis is affecting millions of people in US cities, yet the implications for urban dwellers’ well-being and social reproduction remain less clear. This Article presents a longitudinal analysis of household access to running water—a vital component of social infrastructure—in the 50 largest US cities since 1970. The results indicate that water access has worsened in an increasing number and typology of US cities since the 2008 global financial crash, disproportionately affecting households of color in 12 of the 15 largest cities. We provide evidence to suggest that a ‘reproductive squeeze’—systemic, compounding pressures on households’ capacity to reproduce themselves on a daily and societal basis—is forcing urban households into more precarious living arrangements, including housing without running water. We analyze the case study of Portland (Oregon) to illustrate the racialized nature of the reproductive squeeze under a housing crisis. Our insights reveal that plumbing poverty—a lack of household running water—is expanding in scope and severity to a broader array of US cities, raising doubts about equitable progress towards Sustainable Development Goals for clean water and sanitation for all (SDG 6) and sustainable cities (SDG 11) in an increasingly urbanized United States.
Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma
Dissecting the spatial heterogeneity of cancer-associated fibroblasts (CAFs) is vital for understanding tumor biology and therapeutic design. By combining pathological image analysis with spatial proteomics, we revealed two stromal archetypes in hepatocellular carcinoma (HCC) with different biological functions and extracellular matrix compositions. Using paired single-cell RNA and epigenomic sequencing with Stereo-seq, we revealed two fibroblast subsets CAF-FAP and CAF-C7, whose spatial enrichment strongly correlated with the two stromal archetypes and opposing patient prognosis. We discovered two functional units, one is the intratumor inflammatory hub featured by CAF-FAP plus CD8_PDCD1 proximity and the other is the marginal wound-healing hub with CAF-C7 plus Macrophage_SPP1 co-localization. Inhibiting CAF-FAP combined with anti-PD-1 in orthotopic HCC models led to improved tumor regression than either monotherapy. Collectively, our findings suggest stroma-targeted strategies for HCC based on defined stromal archetypes, raising the concept that CAFs change their transcriptional program and intercellular crosstalk according to the spatial context.
Engineering bone/cartilage organoids: strategy, progress, and application
The concept and development of bone/cartilage organoids are rapidly gaining momentum, providing opportunities for both fundamental and translational research in bone biology. Bone/cartilage organoids, essentially miniature bone/cartilage tissues grown in vitro, enable the study of complex cellular interactions, biological processes, and disease pathology in a representative and controlled environment. This review provides a comprehensive and up-to-date overview of the field, focusing on the strategies for bone/cartilage organoid construction strategies, progresses in the research, and potential applications. We delve into the significance of selecting appropriate cells, matrix gels, cytokines/inducers, and construction techniques. Moreover, we explore the role of bone/cartilage organoids in advancing our understanding of bone/cartilage reconstruction, disease modeling, drug screening, disease prevention, and treatment strategies. While acknowledging the potential of these organoids, we discuss the inherent challenges and limitations in the field and propose potential solutions, including the use of bioprinting for organoid induction, AI for improved screening processes, and the exploration of assembloids for more complex, multicellular bone/cartilage organoids models. We believe that with continuous refinement and standardization, bone/cartilage organoids can profoundly impact patient-specific therapeutic interventions and lead the way in regenerative medicine.
Type 2 immunity in allergic diseases
Significant advancements have been made in understanding the cellular and molecular mechanisms of type 2 immunity in allergic diseases such as asthma, allergic rhinitis, chronic rhinosinusitis, eosinophilic esophagitis (EoE), food and drug allergies, and atopic dermatitis (AD). Type 2 immunity has evolved to protect against parasitic diseases and toxins, plays a role in the expulsion of parasites and larvae from inner tissues to the lumen and outside the body, maintains microbe-rich skin and mucosal epithelial barriers and counterbalances the type 1 immune response and its destructive effects. During the development of a type 2 immune response, an innate immune response initiates starting from epithelial cells and innate lymphoid cells (ILCs), including dendritic cells and macrophages, and translates to adaptive T and B-cell immunity, particularly IgE antibody production. Eosinophils, mast cells and basophils have effects on effector functions. Cytokines from ILC2s and CD4+ helper type 2 (Th2) cells, CD8 + T cells, and NK-T cells, along with myeloid cells, including IL-4, IL-5, IL-9, and IL-13, initiate and sustain allergic inflammation via T cell cells, eosinophils, and ILC2s; promote IgE class switching; and open the epithelial barrier. Epithelial cell activation, alarmin release and barrier dysfunction are key in the development of not only allergic diseases but also many other systemic diseases. Recent biologics targeting the pathways and effector functions of IL4/IL13, IL-5, and IgE have shown promising results for almost all ages, although some patients with severe allergic diseases do not respond to these therapies, highlighting the unmet need for a more detailed and personalized approach.
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