Hematopoietic aging promotes cancer by fueling IL-1⍺-driven emergency myelopoiesis.

Age is a major risk factor for cancer, but how aging impacts tumor control remains unclear. Here, we establish that aging of the immune system, regardless of the age of the stroma and tumor, drives lung cancer progression. Hematopoietic aging enhances emergency myelopoiesis, resulting in the local accumulation of myeloid progenitor-like cells in lung tumors. These cells are a major source of IL-1⍺ that drives the enhanced myeloid response. The age-associated decline of DNMT3A enhances IL-1⍺ production, and disrupting IL-1R1 signaling early during tumor development normalized myelopoiesis and slowed the growth of lung, colonic, and pancreatic tumors. In human tumors, we identified an enrichment for IL-1⍺-expressing monocyte-derived macrophages linked to age, poorer survival, and recurrence, unraveling how aging promotes cancer and offering actionable therapeutic strategies.

Remote vision testing of central retinal acuity and comparison with clinic-based Snellen acuity testing in patients followed for retinal conditions.

Introduction: The unmet need for remote monitoring of visual function with home-based, patient-centric technologies became increasingly palpable during the COVID-19 pandemic. Many patients with chronic eye conditions lack access to office-based examinations. Here, we evaluate the efficacy of the Accustat® test, a virtual application for measuring near visual acuity on any portable electronic device via telehealth. Materials and methods: Thirty-three adult subjects from the telehealth remote monitoring service of a retina practice performed the Accustat® acuity testing at home. All patients underwent in-office general eye examination with additional fundoscopic examination and optical coherence tomography retina imaging. Best corrected visual acuity assessment using a Snellen chart was compared with remote visual acuity assessment with the Accustat® test. Visual acuity was analyzed and compared between the best-corrected near visual acuity potential achieved on the Accustat® and in-office distance best-corrected Snellen visual acuity. Results: The mean logarithm of the minimum angle of resolution (logMAR) visual acuities of all eyes tested using the Accustat test was 0.19 ± 024 and for the office Snellen test 0.21 ± 0.21. A linear regression model with 95% confidence intervals reveals that there is a strong linear relationship between Accustat logMAR and office Snellen logMAR. Bland-Altman analysis demonstrated 95.2% significant agreement between Accustat and Office Snellen's best corrected visual acuity. Intraclass correlation coefficient (ICC = 0.94) demonstrated a strong positive correlation between at home versus office visual acuity. Conclusion: There was a high correlation between the visual acuity measured with the Accustat near vision digital self-test and the office Snellen acuity test, suggesting the potential utility of scalable remote monitoring of central retinal function via telehealth.

Preservation of vision after CaMKII-mediated protection of retinal ganglion cells.

Retinal ganglion cells (RGCs) are the sole output neurons that transmit visual information from the retina to the brain. Diverse insults and pathological states cause degeneration of RGC somas and axons leading to irreversible vision loss. A fundamental question is whether manipulation of a key regulator of RGC survival can protect RGCs from diverse insults and pathological states, and ultimately preserve vision. Here, we report that CaMKII-CREB signaling is compromised after excitotoxic injury to RGC somas or optic nerve injury to RGC axons, and reactivation of this pathway robustly protects RGCs from both injuries. CaMKII activity also promotes RGC survival in the normal retina. Further, reactivation of CaMKII protects RGCs in two glaucoma models where RGCs degenerate from elevated intraocular pressure or genetic deficiency. Last, CaMKII reactivation protects long-distance RGC axon projections in vivo and preserves visual function, from the retina to the visual cortex, and visually guided behavior.

3D Bioprinting of Vascularized Tissues for in vitro and in vivo Applications.

With a limited supply of organ donors and available organs for transplantation, the aim of tissue engineering with three-dimensional (3D) bioprinting technology is to construct fully functional and viable tissue and organ replacements for various clinical applications. 3D bioprinting allows for the customization of complex tissue architecture with numerous combinations of materials and printing methods to build different tissue types, and eventually fully functional replacement organs. The main challenge of maintaining 3D printed tissue viability is the inclusion of complex vascular networks for nutrient transport and waste disposal. Rapid development and discoveries in recent years have taken huge strides toward perfecting the incorporation of vascular networks in 3D printed tissue and organs. In this review, we will discuss the latest advancements in fabricating vascularized tissue and organs including novel strategies and materials, and their applications. Our discussion will begin with the exploration of printing vasculature, progress through the current statuses of bioprinting tissue/organoids from bone to muscles to organs, and conclude with relevant applications for in vitro models and drug testing. We will also explore and discuss the current limitations of vascularized tissue engineering and some of the promising future directions this technology may bring.