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Eighteen percent knew the benefit of LCS, and 69% were not aware of any screening harms. CONCLUSIONS LCS-eligible nonparticipants are more likely to be female, active smokers, have fewer total pack-years of smoking, chronic kidney disease, a history of prior malignancy, and not have chronic obstructive pulmonary disease, coronary artery disease, or liver disease. Targeted education about the benefits and harms of LCS, verification of insurance coverage, and providing convenient screening locations may improve participation. Alzheimer's disease (AD) is the most common cause of dementia, characterised by advanced cognitive and memory deterioration with no effective treatments available. Previous in vitro and in vivo studies suggest that paeoniflorin (PF), a major bioactive constituent of Radix Paeoniae, might possess anti-dementia properties; however, the underlying mechanism remains unclear. The aim of the current study was to determine the therapeutic effects of PF in a transgenic mouse model of AD and to identify its mechanism. Transgenic mice with five familial AD mutations (5XFAD) were used in this study. We showed that 28 days of PF (5 mg/kg, ip) treatment significantly decreased the escape latency and path length in the Morris water maze test and increased the alternation rate in the T-maze test, compared to the vehicle treatment group. In addition, PF treatment significantly alleviated amyloid β plaque burden, inhibited astrocyte activation, and decreased IL-1β and TNF-α expression in the brain of 5XFAD mice. However, the anti-cognitive deficits, anti-amyloidogenic, and anti-inflammatory effects of PF were abolished by 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 0.3 mg/kg), an adenosine A1 receptor (A1R) antagonist. In conclusion, our results suggest that PF might act as a potential therapeutic agent for AD via activation of adenosine A1R. Pathologic intracellular inclusions formed from polymers of misfolded α-synuclein (αsyn) protein define a group of neurodegenerative diseases termed synucleinopathies which includes Parkinson's disease (PD). Prion-like recruitment of endogenous cellular αsyn has been demonstrated to occur in animal models of synucleinopathy, whereby misfolded αsyn can induce further pathologic αsyn inclusions to form through a prion-like mechanism. It has been suggested that misfolded αsyn may assume differing conformations which lead to varied clinical and pathological manifestations of disease; this phenomenon bears similarities to that of prion strains whereby the same misfolded protein can produce unique diseases. It is unclear what factors influence the development of unique αsyn strains, however post-translational modifications (PTMs) such as phosphorylation and truncation that are present in misfolded αsyn in disease may play a role due to their modulation of biochemical and structural αsyn properties. Herein, we investigate the prion-like properties of misfolded αsyn polymers containing either phosphomimetic (S129E) αsyn, 5 different major carboxy (C)-truncated forms of αsyn (1-115, 1-119, 1-122, 1-125, and 1-129 αsyn), or a mixture of these PTM containing αsyn forms compared to full-length (FL) αsyn in HEK293T cells and M83 transgenic mice overexpressing A53T αsyn. It is demonstrated that upon peripheral intramuscular injection of these C-truncated or S129E αsyn polymers into M83 mice, prion-like progression and time to disease onset in this mouse model is elongated when any of these PTMs are present, demonstrating that common modifications to the C-terminus of αsyn present in disease modulates the prion-like seeding properties of αsyn. Intracerebral hemorrhage (ICH) causes neurological function deficit due to the loss of neurons surrounding the hematoma. Acetyldinaline Increased neurogenesis of endogenous neural stem cells (EnNSCs) is believed to increase cell proliferation and differentiation, thereby improving the neurological deficit. However, there are still limited drugs that are effective for treating neurological deficit. So, the effects of compound K (CK) in EnNSCs were measured after thrombin-induced mice models both in vivo and in vitro, and investigated the probable mechanisms of CK during pro-neurogenesis. The results revealed that 10 μM CK promotes neurogenesis, proliferation and reduces apoptosis of EnNSCs after induction by thrombin. After that, CK treatment increased the neurogenesis of EnNSCs through liver X receptor α (LXRα) signaling pathway using adeno-associated virus knockdown and knocked out mice of LXRα gene. Finally, intraperitoneal injection of 10 mg/kg CK improved the neurogenesis of subventricular zone (SVZ), myelin repair and behavioral deficit after stereotaxic injection of thrombin in the basal ganglia of mice, and this process involved LXRα. These observations provided evidence regarding the effect of CK in pro-neurogenesis via LXRα activation, and suggested further evaluation of it due to its potential role as an effective modulator in the treatment of ICH. V.The biochemical and molecular substrates of methamphetamine (METH) use disorder remain to be elucidated. In rodents, increased METH intake is associated with increased expression of dopamine D1 receptors (D1R) in the dorsal striatum. The present study assessed potential effects of inhibiting striatal D1R activity on METH self-administration (SA) by rats. We microinjected Cre-activated adeno-associated viruses to deliver the inhibitory DREADD construct, hM4D (Gi) - mCherry, into neurons that expressed Cre-recombinase (D1-expressing neurons) in the dorsal striatum of male and female transgenic Long Evans rats (Drd1a-iCre#3). Two weeks later, we trained rats to self-administer METH. Once this behavior was acquired, intraperitoneal injections of clozapine-N-Oxide (CNO) or its vehicle (sterile water) were given to rats before each METH SA session to determine the effect of DREADD-mediated inhibition on METH intake. After the end of the experiments, histology was performed to confirm DREADD delivery into the dorsal striatum. There were no significant effects of the inhibitory DREADD on METH SA by male or female rats. Post-mortem histological assessment revealed DREADD expression in the dorsal striatum. Our results suggest that inhibition of D1R in the dorsal striatum does not suppress METH SA. It remains to be determined if activating D1R-expressing neurons might have differential behavioral effects. Future studies will also assess if impacting D1R activity in other brain regions might influence METH SA.