ALKBH3 inhibition normalizes neovessels by reprogramming endothelial fate in diabetic microvasculopathy.

August 25, 2026| Source: Proceedings of the National Academy of Sciences of the United States of America

Diabetic microvasculopathy is a serious diabetes complication, with diabetic retinopathy (DR) being a leading cause of blindness worldwide due to immature, leaky neovessels. Antiangiogenic therapies merely suppress neovascularization, leaving the retina oxygen-starved and prone to regrowth. Thus, therapies that stabilize aberrant neovessels are needed. We identify the RNA demethylase ALKBH3 as an epitranscriptional driver of diabetic microvasculopathy. Upregulated ALKBH3 in diabetic vascular endothelial cells promoted a pathological shift to an unstable, pro-angiogenic phenotype, disrupting blood-retinal barrier and forming immature neovessels, which impaired vision. Conversely, removing ALKBH3 protected against this. Mechanistically, ALKBH3 demethylated BMP2 mRNA to increase its stability via YTHDF2. We further developed a neovasculature-targeting nanoparticle delivering the ALKBH3 inhibitor HUHS015, which normalized retinal neovascularization by simultaneously limiting growth and promoting maturation. It acted synergistically with vascular endothelial growth factor (VEGF) blockade, suggesting potential for anti-VEGF-resistant cases. Our work defines ALKBH3 as a key mediator of diabetic microvasculopathy and supports a VEGF-independent therapeutic paradigm that shifts the focus from vessel suppression to active normalization.

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The honey bee stinger: An unusual pump with collapsible double pistons.

Most stinging animals deliver venom by contracting muscles around a venom reservoir, but honey bees employ a fundamentally different strategy. The stingers of worker bees have the unique ability to autotomize, separating from the body, to continue to sting independently. Despite more than a century of anatomical descriptions, the mechanics of venom pumping have remained unresolved due to the challenges of observing them in action. We recorded high-speed videos of active, autotomized stingers, co

Health & MedicineOctober 20, 2026

Chronic cigarette smoke exposure induces distinct stem cell states driving genetic driver-specific non-small cell lung cancer subtypes.

Cigarette smoke-induced chronic inflammation (CI) potentiates development of non-small cell lung cancer (NSCLC) by mediating genetic and epigenetic events. Using normal lung organoids (LOs), we define how chronic cigarette smoke condensate (CSC) exposure drives two separate stem cell populations to evolve premalignant states harboring progressive epigenetic and linked transcriptomic abnormalities in the absence of major driver mutations. These dynamics facilitate evolution of an immune evasive s

Health & MedicineOctober 13, 2026

Extended fractional Hofstadter states at high field in twisted bilayer graphene above the magic angle.

When a Chern band is partially filled, a fractional Chern insulator (FCI)-the lattice analog of a fractional quantum Hall state-can arise. Though the full range of possible scenarios for producing such a state is not established, the most tractable models combine strong electronic interactions with the quantum geometry of the parent Chern band meeting specific criteria. In twisted bilayer graphene, the importance of interactions can be tuned by varying the interlayer twist. Here, we study a samp

Health & MedicineOctober 13, 2026

Phenotypic screening identifies kenpaullone as a prolymphangiogenic compound to improve heart repair following myocardial infarction.

Myocardial infarction (MI) induces cardiac muscle death and its subsequent replacement by a noncontractile fibrotic scar, which underlies progression to heart failure. Current treatments restore blood flow and assist with cardiac workload but do not promote regeneration. We have previously shown endogenous growth of the cardiac lymphatic system following MI and further stimulation with the lymphatic endothelial specific mutated Vascular Endothelial Growth Factor-C (VEGF-C) isoform, VEGFC-C156S,

Health & MedicineOctober 13, 2026

Dopamine suppresses pathological retinal oscillations and enhances the signal-to-noise ratio.

Infantile nystagmus is a debilitating involuntary eye movement disorder often associated with retinal diseases such as congenital stationary night blindness (CSNB). The oscillating eye movements of infantile nystagmus come with reduced visual acuity and strongly impair quality of life. No cure exists for this condition. Previously, we demonstrated that nystagmus in the CSNB mouse model Nyx nob has a retinal cause. Specifically, we found that synchronized oscillations of retinal ganglion cells (R