flaksesomlys

Interesting:

2025 Dec 31: DwarkeshPatel YT fea. Sarah Paine: Human Rights Killed Communism - Sarah Paine:



BTW, that's Sarah C. M. Paine, until very recently the William S. Sims University Professor of History and Grand Strategy and the Ernest J. King Professor of Maritime History, both, at the US Naval War College. She's an incredibly interesting speaker. Recommended.

(Dwarkesh Patel is this random dude who mistakenly thinks he's a podcaster and keeps trying to have other guests, but in actuality was put on Earth to bring Paine to the masses. He's got something like 14 hours of her up on his channel.)

"...but it turns out, mining is fun."

2025 Dec 26: Engineer Everything (user Engineer.Everything-i5g) on YT: Shall I go still deeper? #engineering #Minecraft #tunnel #mining #constr...

2025 Dec 24: ScienceDaily [press release?]: "Scientists reverse Alzheimer’s in mice and restore memory":

By examining both human Alzheimer's brain tissue and multiple preclinical mouse models, the team identified a key biological failure at the center of the disease. They found that the brain's inability to maintain normal levels of a critical cellular energy molecule called NAD+ plays a major role in driving Alzheimer's. Importantly, maintaining proper NAD+ balance was shown to not only prevent the disease but also reverse it in experimental models.

Continuing from the article:

NAD+ levels naturally decline throughout the body, including the brain, as people age. When NAD+ drops too low, cells lose the ability to carry out essential processes needed for normal function and survival. The researchers discovered that this decline is far more severe in the brains of people with Alzheimer's. The same pattern was seen in mouse models of the disease.

[...]

Amyloid and tau abnormalities are among the earliest and most significant features of Alzheimer's. In both mouse models, these mutations led to widespread brain damage that closely mirrors the human disease. This included breakdown of the blood-brain barrier, damage to nerve fibers, chronic inflammation, reduced formation of new neurons in the hippocampus, weakened communication between brain cells, and extensive oxidative damage. The mice also developed severe memory and cognitive problems similar to those seen in people with Alzheimer's.

[...]

This approach built on the group's earlier work published in Proceeding of the National Academy of Sciences USA, which showed that restoring NAD+ balance led to both structural and functional recovery after severe, long-lasting traumatic brain injury. In the current study, the researchers used a well-characterized pharmacologic compound called P7C3-A20, developed in the Pieper laboratory, to restore NAD+ balance.

The results were striking. Preserving NAD+ balance protected mice from developing Alzheimer's, but even more surprising was what happened when treatment began after the disease was already advanced. In those cases, restoring NAD+ balance allowed the brain to repair the major pathological damage caused by the genetic mutations.

Both mouse models showed complete recovery of cognitive function. This recovery was also reflected in blood tests, which showed normalized levels of phosphorylated tau 217, a recently approved clinical biomarker used to diagnose Alzheimer's in people. These findings provided strong evidence of disease reversal and highlighted a potential biomarker for future human trials.

Note, potential conflict of interest: the head of the lab, Dr Pieper, above, has a serious commercial interest in this proving out:

The technology is currently being commercialized by Glengary Brain Health, a Cleveland-based company co-founded by Dr. Pieper.

The actual research article:

2025 Dec 22: Cell Reports Medicine [peer-reviewed scientific journal]: Pharmacologic reversal of advanced Alzheimer's disease in mice and identification of potential therapeutic nodes in human brain by Kalyani Chaubey et al. (+35 other authors!):

Abstract:

Alzheimer's disease (AD) is traditionally considered irreversible. Here, however, we provide proof of principle for therapeutic reversibility of advanced AD. In advanced disease amyloid-driven 5xFAD mice, treatment with P7C3-A20, which restores nicotinamide adenine dinucleotide (NAD+) homeostasis, reverses tau phosphorylation, blood-brain barrier deterioration, oxidative stress, DNA damage, and neuroinflammation and enhances hippocampal neurogenesis and synaptic plasticity, resulting in full cognitive recovery and reduction of plasma levels of the clinical AD biomarker p-tau217. P7C3-A20 also reverses advanced disease in tau-driven PS19 mice and protects human brain microvascular endothelial cells from oxidative stress. In humans and mice, pathology severity correlates with disruption of brain NAD+ homeostasis, and the brains of nondemented people with Alzheimer's neuropathology exhibit gene expression patterns suggestive of preserved NAD+ homeostasis. Forty-six proteins aberrantly expressed in advanced 5xFAD mouse brain and normalized by P7C3-A20 show similar alterations in human AD brain, revealing targets with potential for optimizing translation to patient care.

Full text here: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00608-1