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CONCLUSION: Contrary to our hypothesis, older adults displayed more efficient heat-CPM, independent of chronic pain. Similarly, motor unit control was mostly influenced by age but not chronic knee pain. These findings suggest that age-related changes in pain modulation and motor unit behavior may play a greater role in neuromuscular function than the presence of chronic pain itself.

Fewer papers are reporting findings on the border of statistical significance, a potential marker of dodgy research practices

Data gaps come as Arctic sea ice shrinks to near-record lows

In this issue, Chadarevian et al. showed that engraftment of human iPSC-derived microglia (iMG) engineered to express secreted neprilysin (sNEP) under the plaque-responsive CD9 promoter reduces amyloid burden, neuronal damage, and inflammation in an Alzheimer's disease (AD) mouse model.¹ These findings establish a cell-based strategy to treat neurological diseases.

Parkinson's disease (PD), characterized by the selective loss of midbrain dopaminergic neurons (mDANs), is a promising target for cell replacement therapy. Two recent clinical trials¹^(,)² published in Nature report the safety and potential efficacy of human pluripotent stem cell-based approaches, representing a major milestone in regenerative medicine for PD.

N⁶-methyladenosine (m6A) is an abundant internal RNA modification that can impact gene expression at both post-transcriptional and transcriptional levels. However, the landscapes and functions of m6A in human brains and neurodegenerative diseases, including Alzheimer's disease (AD), are under-explored. Here, we examined RNA m6A methylome using total RNA-seq and meRIP-seq in middle frontal cortex of post-mortem brains from individuals with or without AD, which revealed m6A alteration on both...

Recent work leveraging artificial intelligence has offered promise to dissect disease heterogeneity by identifying complex intermediate brain phenotypes, called dimensional neuroimaging endophenotypes (DNEs). We advance the argument that these DNEs capture the degree of expression of respective neuroanatomical patterns measured, offering a dimensional neuroanatomical representation for studying disease heterogeneity and similarities of neurologic and neuropsychiatric diseases. We investigate the...

Tracking the envelope of speech in the brain is important for speech comprehension. Recent research suggests that acoustic background noise can enhance neural speech tracking, enabling the auditory system to robustly encode speech even under unfavorable conditions. Aging and hearing loss are associated with internal, neural noise in the auditory system, raising the question whether additional acoustic background noise enhances neural speech tracking in older adults. In the current...

Pathological events often impact tissue regions in a spatially variable manner, making it challenging to identify therapeutic targets. Spatial transcriptomics (ST) is a powerful technology to map spatially variable molecular mechanisms, yet suitable analytical methods have been lacking. We introduce spatially resolved pathology score (SPaSE), an optimal transport-based algorithm to compare ST data from diseased and control tissues. SPaSE computes a "pathology score" for each spot in the diseased...

CONCLUSIONS AND IMPLICATIONS: Vitamin D supplementation produced no measurable improvement in cognitive outcomes in older adults with mild to moderate vitamin D deficiency. The remote trial methodology provides an innovative approach to large-scale trials.

CONCLUSIONS AND IMPLICATIONS: Adherence to plant-based dietary patterns was associated with a lower likelihood of being on an unfavorable depressive trajectory, whereas an unhealthy plant-based diet was associated with an increased likelihood of being on an unfavorable depressive trajectory.

CONCLUSIONS AND IMPLICATIONS: Although health profiles may help identify conditions most likely impacting health of PWH, frailty may be key to identifying those having the highest needs and at risk for greater home time loss following SNF stays, with this impact varying by age.

CONCLUSIONS AND IMPLICATIONS: Community-based frailty management strategies should consider a broader range of psychological factors, such as mental vitality, apathy, and mental well-being. Further research is needed to explore additional psychological dimensions beyond depression and anxiety, and their relationship with frailty and aging-related health outcomes.

BACKGROUND: Given trends towards greater life expectancy, there is an increasing need to promote healthy ageing and add quality and value to older adults' lives, however the evidence regarding the effects on overall health and wellbeing has not been synthesised. Active lifestyles may provide diverse health and wellbeing benefits for older adults in terms of maintaining or improving their physical, psychological, and social functions. This systematic review evaluates whether and how different...

Post-translational modifications (PTMs) regulate protein homeostasis, but how aging impacts PTMs remains unclear. Here, we used mass spectrometry to reveal changes in hundreds of protein ubiquitylation, acetylation, and phosphorylation sites in the mouse aging brain. We show that aging has a major impact on protein ubiquitylation. 29% of the quantified ubiquitylation sites were affected independently of protein abundance, indicating altered PTM stoichiometry. Using iPSC-derived neurons, we...

Ceramic circuit boards (CCBs) have been extensively utilized in 5G communications, aerospace, and artificial intelligence due to their excellent thermal conductivity and electrical performance. However, due to the limitation of manufacturing technologies, the existing CCBs can not take into account both the resolution and thickness, which restricts the miniaturization and high power of the resulting electronics. Herein, we report a standing-CCBs (S-CCBs) with both high-resolution and high...

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Disruption in neuronal and synaptic metabolic homeostasis is a key driver of neurodegeneration in Parkinson's disease (PD). Mitochondrial activity, biomass, and efficiency are critical to this balance. While activity and biomass are well characterized in PD pathology, mitochondrial metabolic efficiency remains insufficiently explored. Our previous studies showed that the protein product of PD-associated gene DJ-1 modulates metabolic efficiency through its interaction with the F1Fo-ATP-synthase β...

Duplication of the SNCA gene (SNCA^(Dupl)), linked to elevated levels of α-synuclein (aSyn), is a genetic cause of Parkinson's disease (PD). Our prior work with human-induced pluripotent stem cell (hiPSC)-derived midbrain neurons generated from patients with PD SNCA^(Dupl) identified neuritic deficits, accompanied by decreased levels of cytoskeletal element β-tubulin-III (bTubIII). To explore mechanisms underlying these effects in SNCA^(Dupl) neurons, we used CRISPR-Cas9 to generate isogenic...