•We focuses on seven commonly used hypnotics to analyze the effects of long- and short-term use on adults and older adults.•Main outcomes are total sleep time, sleep efficiency, sleep latency and ...WASO.•ORAs can be widely used in adults and the elderly, and both short-term and long-term use are effective for primary insomnia.•H1-antagonists are more effective in adults than in the elderly.•As a food supplement, melatonin has little effect on adults, but it still has a certain effect on the elderly.
This study focuses on seven commonly used hypnotics to comprehensively analyze the effects of long- and short-term use on sleep outcomes among adults and older adults.
A network meta-analysis was performed. The insomnia medications were classified into seven categories: benzodiazepines, z-drugs, melatonin, H1-antagonists, orexin receptor antagonists (ORAs), antidepressants, and anticonvulsants. We compared their efficacy of total sleep time, sleep latency, sleep efficiency and wake after sleep onset in subgroups short-term, long-term, elderly, and adults.
A total of 111 RCTs involving 25,923 participants were included in this study.
ORAs can be widely used in adults and the elderly, and both short-term and long-term use are effective for primary insomnia. H1-antagonists are more effective in adults than in the elderly. Although benzodiazepines have a more obvious effect on sleep maintenance, it is best to reduce their use due to their side effects, especially for the elderly. As a food supplement, melatonin has little effect on adults, but it still has a certain effect on the elderly.
Background & Aims Non-alcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride (TG) contents. The prevalence of NAFLD is increased with aging. However, the ...molecular mechanism for aging-induced fatty liver remains poorly understood. Methods Hepatic TG contents and gene expression profiles were analyzed in body weight-matched young (2 months), middle (8 months) and old (18 months) C57BL/6 mice. Endoplasmic reticulum (ER) stress and farnesoid X receptor (FXR) expression were examined. The mechanism of ER stress activation in the regulation of FXR expression was further investigated. Results In the present study, we found that TG was markedly accumulated and lipogenic genes were up-regulated in the liver of C57BL/6 mice aged 18 months. FXR, a key regulator of hepatic lipid metabolism was down-regulated in these old mice. At molecular levels, ER stress was activated in old mice and repressed FXR expression through inhibition of hepatocyte nuclear factor 1 alpha (HNF1α) transcriptional activity. Conclusions Our findings demonstrate that FXR down-regulation plays a critical role in aging-induced fatty liver.
Post-translational modifications (PTMs) allot versatility to the biological functions of highly conserved proteins. Recently, modifications to non-histone proteins such as methylation, acetylation, ...phosphorylation, glycosylation, ubiquitination, and many more have been linked to the regulation of pivotal pathways related to cellular response and stability. Due to the roles these dynamic modifications assume, their dysregulation has been associated with cancer and many other important diseases such as inflammatory disorders and neurodegenerative diseases. For this reason, we present a review and perspective on important post-translational modifications on non-histone proteins, with emphasis on their roles in diseases and small molecule inhibitors developed to target PTM writers. Certain PTMs' contribution to epigenetics has been extensively expounded; yet more efforts will be needed to systematically dissect their roles on non-histone proteins, especially for their relationships with nononcological diseases. Finally, current research approaches for PTM study will be discussed and compared, including limitations and possible improvements.
The combination of transition‐metal catalysis and organocatalysis increasingly offers chemists opportunities to realize diverse unprecedented chemical transformations. By combining iridium with ...chiral thiourea catalysis, direct enantioselective reductive cyanation and phosphonylation of secondary amides have been accomplished for the first time for the synthesis of enantioenriched chiral α‐aminonitriles and α‐aminophosphonates. The protocol is highly efficient and enantioselective, providing a novel route to the synthesis of optically active α‐functionalized amines from the simple, readily available feedstocks. In addition, the reactions are scalable and the thiourea catalyst can be recycled and reused.
The first enantioselective reductive cyanation and phosphonylation of secondary amides have been achieved by the combination of iridium with chiral thiourea catalysis. The protocol is highly efficient and enantioselective, providing a novel route for the synthesis of optically active α‐aminonitriles and α‐aminophosphonates from bench‐stable feedstocks.
Molecular sieving is of great importance to proton exchange in fuel cells, water desalination, and gas separation. Two-dimensional crystals emerge as superior materials showing desirable molecular ...permeability and selectivity. Here we demonstrate that a graphdiyne membrane, an experimentally fabricated member in the graphyne family, shows superior proton conductivity and perfect selectivity thanks to its intrinsic nanomesh structure. The trans-membrane hydrogen bonds across graphdiyne serve as ideal channels for proton transport in Grotthuss mechanism. The free energy barrier for proton transfer across graphdiyne is ~2.4 kJ mol
, nearly identical to that in bulk water (2.1 kJ mol
), enabling "transparent" proton transport at room temperature. This results in a proton conductivity of 0.6 S cm
for graphdiyne, four orders of magnitude greater than graphene. Considering its ultimate pore size of 0.55 nm, graphdiyne membrane blocks soluble fuel molecules and exhibits superior proton selectivity. These advantages endow graphdiyne a great potential as proton exchange material.
Phenotypic transformation and excessive proliferation of pulmonary arterial smooth muscle cells (PASMCs) play an important role in vascular remodeling during pulmonary hypertension (PH). Magnolol ...(5,5′-diallyl-2,2′-dihydroxybiphenyl) is the major bioactive constituent isolated from the bark of Magnolia Officinalis, which has anti-inflammatory, antioxidant, and cardiovascular protection effects. However, the effect of magnolol on the phenotypic transformation of PASMCs is still unknown. This study aims to evaluate the effects of magnolol on the phenotypic transformation of PASMCs induced by hypoxia. In vivo, Sprague Dawley rats were exposed to hypoxia (10% O2) for four weeks to establish a PH model. The results showed that hypoxia treatment led to an increase in right ventricle systolic pressure, Fulton index, collagen production, accompanied by upregulation in the expression of collagen Ⅰ, collagen Ⅲ, OPN, PCNA, CyclinD1, p-JAK2, and p-STAT3, as well as decreases in expression of SM-22α; these changes were attenuated by magnolol. In vitro, the primary cultured PASMCs were exposed to 3% O2 for 48 h to induce phenotypic transformation. Consistent with the findings in vivo, magnolol treatment could prevent the phenotypic transformation and hyperproliferation of PASMCs induced by hypoxia, accompanied by downregulation in the expression of p-JAK2 and p-STAT3. In summary, this study demonstrated that the protective effect of magnolol on PH vascular remodeling is related to the inhibition of phenotypic transformation and hyperproliferation of PASMCs by inhibiting the JAK2/STAT3 pathway.
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•Magnolol inhibits vascular remodeling and collagen deposition in hypoxic PH rats.•Magnolol inhibits the hypoxia-induced phenotypic transformation of PASMCs in vitro.•Magnolol inhibits the hypoxia-induced proliferation and migration of PASMCs in vitro.•The mechanism is related to inhibiting the activation of the JAK2/STAT3 pathway.
The Toll-like receptor (TLR) 4 signalling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signalling in colon tumourigenesis, we examined the ...expression of TLR4 and myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC).
The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal mucosae was evaluated by immunohistochemistry, and the correlations between their immunoscores and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analysed.
Compared with normal mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23% cancers showed high expression of MyD88. The high expression of TLR4 and MyD88 was significantly correlated with liver metastasis (P=0.0001, P=0.0054). In univariate analysis, the high expression of TLR4 was significantly associated with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15-4.07; P=0.015). The high expression of MyD88 expression was significantly associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31-4.13; P=0.0038 and HR: 3.03; 95% CI: 1.67-5.48; P=0.0002). The high combined expression of TLR4 and MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI: 1.27-3.99; P=0.0053 and HR: 2.97; 95% CI: 1.64-5.38; P=0.0003). Multivariate analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI: 0.99-3.55; P=0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01-3.67; P=0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17-4.33; P=0.0112) were independent prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was strongly associated with both poor DFS and OS.
Our findings suggest that high expression of TLR4 and MyD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with CRC.
Image segmentation is widely used in life. Generally speaking, the segmentation results are divided into good and bad quality, so it is very important to propose an effective method to evaluate the ...quality of image segmentation. This paper proposed a framework based on edge detection and feature extraction for evaluating the quality of image segmentation. The framework belongs to unsupervised evaluation, the operation is simple and easy to implement, and readers can add or subtract methods in the framework according to specific circumstances. To prove the effectiveness of the proposed framework, we tested on four different datasets. In addition, we compare the proposed framework with some classic and newer evaluation methods. Experimental results show that the proposed framework is suitable for many types of images, and its performance is better than some existing metrics.
Recent studies indicate that a subset of cancer cells possessing stem cell properties, referred to as cancer-initiating or cancer stem cells (CSCs), have crucial roles in tumor initiation, metastasis ...and resistance to anticancer therapies. Transforming growth factor (TGF)-β and their family members have been implicated in both normal (embryonic and somatic) stem cells and CSCs. In this study, we observed that exposure to TGF-β increased the population of breast cancer (BC) cells that can form mammospheres in suspension, a feature endowed by stem cells. This was mediated by the micro (mi)RNA family miR-181, which was upregulated by TGF-β at the post-transcriptional level. Levels of the miR-181 family members were elevated in mammospheres grown in undifferentiating conditions, compared with cells grown in two-dimensional conditions. Ataxia telangiectasia mutated (ATM), a target gene of miR-181, exhibited reduced expression in mammospheres and upon TGF-β treatment. Overexpression of miR-181a/b, or depletion of ATM or its substrate CHK2, was sufficient to induce sphere formation in BC cells. Finally, knockdown of ATM enhanced in vivo tumorigenesis of the MDA361 BC cells. Our results elucidate a novel mechanism through which the TGF-β pathway regulates the CSC property by interfering with the tumor suppressor ATM, providing insights into the cellular and environmental factors regulating CSCs, which may guide future studies on therapeutic strategies targeting these cells.
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