The 5-HT Descending Facilitation System Contributes to the Disinhibition of Spinal PKCγ Neurons and Neuropathic Allodynia via 5-HT Receptors.

Neuropathic pain, often featuring allodynia, imposes significant physical and psychological burdens on patients, with limited treatments due to unclear central mechanisms. Addressing this challenge remains a crucial unsolved issue in pain medicine. Our previous study, using protein kinase C gamma (PKCγ)-tdTomato mice, highlights the spinal feedforward inhibitory circuit involving PKCγ neurons in gating neuropathic allodynia.

Development and usability of the "Cognitive Evergreenland" app to engage individuals at high risk of dementia in lifestyle interventions.

Multidomain lifestyle interventions can improve cognitive function and mobile health technologies can deliver cost-effective interventions. We developed the smartphone app, Cognitive Evergreenland, to promote cognitive health in people at high risk of dementia, and assessed its usability. Functional modules were selected using a behaviour change wheel (BCW) theory-based method.

Unspliced XBP1 enhences metabolic reprogramming in colorectal cancer cells by interfering with the mitochondrial localization of MGME1.

Tumor cells undergo metabolic reprogramming, which makes them tend to utilize anaerobic glycolysis rather than oxidation to rapidly produce energy and intermediate products required for proliferation. In this process, mitochondria inevitably undergo corresponding alterations; however, the specific alterations in mitochondria across different cancer types and the mechanisms governing these changes remain poorly understood. This study demonstrated that unspliced X-box binding protein 1 (XBP1-u) inhibits the translocation of mitochondrial genome maintenance exonuclease 1 (MGME1) into mitochondria by binding to the mitochondrial targeting sequence (MTS) of MGME1.

Protective functions of liver X receptor α on calcified aortic valve: involvement of regulating endoplasmic reticulum-mediated osteogenic differentiation.

Aims: Effective therapeutic drugs for calcific aortic valve disease (CAVD) are lacking, although its incidence has been increasing over the past decade, and is predicted to continue rising in the future. This study aimed to explore the role and potential mechanisms of liver X receptor α (LXRα) in CAVD, which offers a promising approach for treating CAVD.

Methods And Results: Osteogenic stimulation was performed following which a substantial downregulation of LXRα was observed in human calcific aortic valves and in valvular interstitial cells.

Dithiothreitol Facilitates LbCas12a with Expanded PAM Preference for Ultrasensitive Nucleic Acid Detection.

Clustered regularly interspaced short palindromic repeats-associated (CRISPR/Cas) proteins have been used for a growing class of in vitro molecular diagnostics due to their modularity and high specificity in targeting nucleic acid. However, the requirement of a protospacer adjacent motif (PAM) for Cas protein-catalyzed trans-cleavage poses a challenge for random nucleic acid detection. Here, we demonstrate that dithiothreitol (DTT) enables LbCas12a to adopt a relaxed preference for PAM base pairing, thereby expanding the target sequence space.