Explore the vast range of titles available.

ObjectivesTo conduct an updated systematic review and meta-analysis of association between sleep and all-cause cognitive disorders.MethodsPubMed and EMBASE were searched from inception to 18 February 2019. Cohort studies exploring longitudinal associations of sleep with cognitive decline or dementia were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment. The robust error meta-regression model was used to conduct the dose–response meta-analysis for sleep duration.Results11 155 reports were searched and 51 eligible cohorts with 15 sleep problems were included for our meta-analyses. Ten types of sleep conditions or parameters, including six (insomnia, fragmentation, daytime dysfunction, prolonged latency, rapid eye movement sleep behaviour disorder and excessive time in bed) with moderate-to-high levels of evidence, were linked to higher risk of all-cause cognitive disorders. Furthermore, a U-shaped relationship was revealed for the associations with sleep duration.ConclusionsSleep management might serve as a promising target for dementia prevention.

ObjectiveInflammation plays a crucial role in the pathogenesis of mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Our study aimed to analyse previous inconsistent results of inflammatory markers in AD and MCI quantitatively.MethodsStudies reporting concentrations of peripheral or cerebrospinal fluid (CSF) markers were included, and eligible data on AD, MCI and control were extracted. Pooled Hedges’s g was adopted to illustrate comparisons, and various confounding factors were used to explore sources of heterogeneity.ResultsA total of 170 studies were included in the meta-analysis and systematic review, which demonstrated increased peripheral levels of high-sensitivity C reactive protein (Hedges’s g 0.281, p<0.05), interleukin-6 (IL-6) (0.429, p<0.005), soluble tumour necrosis factor receptor 1 (sTNFR1) (0.763, p<0.05), soluble tumour necrosis factor receptor 2 (sTNFR2) (0.354, p<0.005), alpha1-antichymotrypsin (α1-ACT) (1.217, p<0.005), IL-1β (0.615, p<0.05) and soluble CD40 ligand (0.868, p<0.005), and CSF levels of IL-10 (0.434, p<0.05), monocyte chemoattractant protein-1 (MCP-1) (0.798, p<0.005), transforming growth factor-beta 1 (1.009, p<0.05), soluble triggering receptor expressed on myeloid cells2 (sTREM2) (0.587, p<0.001), YKL-40 (0.849, p<0.001), α1-ACT (0.638, p<0.001), nerve growth factor (5.475, p<0.005) and visinin-like protein-1 (VILIP-1) (0.677, p<0.005), in AD compared with the control. Higher levels of sTNFR2 (0.265, p<0.05), IL-6 (0.129, p<0.05) and MCP-1 (0.779, p<0.05) and lower levels of IL-8 (−1.293, p<0.05) in the periphery, as well as elevated concentrations of YKL-40 (0.373, p<0.05), VILIP-1 (0.534, p<0.005) and sTREM2 (0.695, p<0.05) in CSF, were shown in MCI compared with the control. Additionally, increased peripheral sTNFR1 (0.582, p<0.05) and sTNFR2 (0.254, p<0.05) levels were observed in AD compared with MCI.ConclusionSignificantly altered levels of inflammatory markers were verified in comparison between AD, MCI and control, supporting the notion that AD and MCI are accompanied by inflammatory responses in both the periphery and CSF.

BackgroundInformation from well-established dementia risk models can guide targeted intervention to prevent dementia, in addition to the main purpose of quantifying the probability of developing dementia in the future.MethodsWe conducted a systematic review of published studies on existing dementia risk models. The models were assessed by sensitivity, specificity and area under the curve (AUC) from receiver operating characteristic analysis.ResultsOf 8462 studies reviewed, 61 articles describing dementia risk models were identified, with the majority of the articles modelling late life risk (n=39), followed by those modelling prediction of mild cognitive impairment to Alzheimer’s disease (n=15), mid-life risk (n=4) and patients with diabetes (n=3). Age, sex, education, Mini Mental State Examination, the Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological assessment battery, Alzheimer’s Disease Assessment Scale-cognitive subscale, body mass index, alcohol intake and genetic variables are the most common predictors included in the models. Most risk models had moderate-to-high predictive ability (AUC>0.70). The highest AUC value (0.932) was produced from a risk model developed for patients with mild cognitive impairment.ConclusionThe predictive ability of existing dementia risk models is acceptable. Population-specific dementia risk models are necessary for populations and subpopulations with different characteristics.

Endometriosis is a chronic inflammatory syndrome and nearly 6%‐10% of women are affected by it during the reproductive period. Previous studies have proved that microRNAs (miRNAs) are implicated in the pathogenesis of ovarian endometriosis. In this study, we aimed to investigate that restored miR‐488 would effectively inhibit the development of endometriosis. The microarray‐based data analysis was performed to screen endometriosis‐related differentially expressed genes (DEGs). The mouse model in endometriosis syndrome was established by being subcutaneously injected with Estradiol benzoate, and the ectopic endometrial tissues and normal endometrial tissues were collected. Additionally, the endometrial glandular epithelial cells were extracted from the endometrial glandular epithelial tissues from normal and endometriosis mice. In order to examine the role of miR‐488 in mice with endometriosis, we measured miR‐488 expression and expression levels of Frizzled‐7 (FZD7), cyclinD1, β‐catenin, and c‐Myc in vivo and in vitro. Finally, we detected the effect of miR‐488 on cell proliferation, apoptosis, migration and invasion in vitro. FZD7 was upregulated in human endometriosis. The data showed higher expression levels of FZD7, β‐catenin, c‐Myc and cyclinD1, and lower miR‐488 expression in mouse endometrial tissues. FZD7 was the target gene of miR‐488. Furthermore, elevated miR‐488 in isolated mouse endometrial glandular endometrial cells inhibited FZD7, the translocation of β‐catenin to nucleus, the activation of Wnt pathway, and the cell proliferation, migration and invasion. Collectively, these findings indicated that up‐regulated miR‐488 may reduce the proliferation, migration and invasion of endometrial glandular epithelial cells through inhibiting the activation of Wnt pathway by down‐regulating FZD7.

Red industrial heritage is a crucial component of global socialist industrial civilization, embodying both industrial memory and revolutionary spirit. However, its preservation faces significant challenges, including insufficient policy attention, homogenized revitalization models, and a lack of systematic research. This study uses Hebei Province, a key region where modern industry and revolutionary history intersect, as a case study. By employing Geographic Information System (GIS) spatial analysis and historical geography, the research explores the spatiotemporal patterns and underlying factors that influence the distribution of red industrial heritage. The findings reveal: (1) the spatial distribution is irregular, exhibiting concentration, with high density in the central and southern parts of Hebei, while the northern and eastern areas are more dispersed; (2) The spatiotemporal evolution aligns with significant historical events; (3) The distribution pattern is shaped by multiple factors, with the dynamics of modern Chinese warfare and historical policies serving as the primary driving forces, interacting with natural geographical factors. This study enhances our comprehension of the significance of red industrial heritage and, based on its spatiotemporal variations, proposes a tiered, sustainable preservation strategy. It provides valuable insights into the preservation of socialist industrial heritage both in China and globally.

The present study contrasts interannual variations in the intensity of boreal summer 10–20-day and 30–60-day intraseasonal oscillations (ISOs) over the tropical western North Pacific and their factors. A pronounced difference is found in the relationship of the two ISOs to El Niño-Southern Oscillation. The 10–20-day ISO intensity is enhanced during El Niño developing summer, whereas the 30–60-day ISO intensity is enhanced during La Niña decaying summer. The above different relationship is interpreted as follows. The equatorial central and eastern Pacific SST anomalies modify vertical wind shear, lower-level moisture, and vertical motion in a southeast-northwest oriented band from the equatorial western Pacific to the tropical western North Pacific where the 10–20-day ISOs originate and propagate. These background field changes modulate the amplitude of 10–20-day ISOs. Preceding equatorial central and eastern Pacific SST anomalies induce SST anomalies in the North Indian Ocean in summer, which in turn modify vertical wind shear and vertical motion over the tropical western North Pacific. The modified background fields influence the amplitude of the 30–60-day ISOs when they reach the tropical western North Pacific from the equatorial region. A feedback of ISO intensity on local SST change is identified in the tropical western North Pacific likely due to a net effect of ISOs on surface heat flux anomalies. This feedback is more prominent from the 10–20-day than the 30–60-day ISO intensity change.

Coptis chinensis is an ancient Chinese herb treating diabetes in China for thousands of years. However, its underlying mechanism remains poorly understood. Here, we report the effects of its main active component, berberine (BBR), on stimulating insulin secretion. In mice with hyperglycemia induced by a high-fat diet, BBR significantly increases insulin secretion and reduced blood glucose levels. However, in mice with hyperglycemia induced by global or pancreatic islet β-cell-specific Kcnh6 knockout, BBR does not exert beneficial effects. BBR directly binds KCNH6 potassium channels, significantly accelerates channel closure, and subsequently reduces KCNH6 currents. Consequently, blocking KCNH6 currents prolongs high glucose-dependent cell membrane depolarization and increases insulin secretion. Finally, to assess the effect of BBR on insulin secretion in humans, a randomized, double-blind, placebo-controlled, two-period crossover, single-dose, phase 1 clinical trial (NCT03972215) including 15 healthy men receiving a 160-min hyperglycemic clamp experiment is performed. The pre-specified primary outcomes are assessment of the differences of serum insulin and C-peptide levels between BBR and placebo treatment groups during the hyperglycemic clamp study. BBR significantly promotes insulin secretion under hyperglycemic state comparing with placebo treatment, while does not affect basal insulin secretion in humans. All subjects tolerate BBR well, and we observe no side effects in the 14-day follow up period. In this study, we identify BBR as a glucose-dependent insulin secretagogue for treating diabetes without causing hypoglycemia that targets KCNH6 channels. Berberine is a compound with glucose-lowering effects in mice and humans. Here, the authors show that in mice berberine has beneficial glycemic effects by promoting insulin secretion, which requires the potassium channel KCNH6 in beta cells, and that berberine can promote insulin secretion in healthy men in a phase 1 clinical trial.

Industrial heritage, as a vital carrier of industrial civilization, is a key resource for advancing regional sustainable development. Understanding its spatial distribution and influencing factors is essential for effective conservation and revitalization. This study examines 207 industrial heritage sites in Hebei Province, one of the birthplaces of modern industry in China. By integrating multiple spatial analytical methods, it explores the spatial patterns and influencing factors of industrial heritage. A progressive analytical framework combining GeoDetector, Ordinary Least Squares, and Geographically Weighted Regression models was established to interpret formation mechanisms from factor identification to global and local heterogeneity. Results show that industrial heritage in Hebei forms high-density clusters along the eastern coast and southwestern hinterland, with lower densities in the north and central regions. The spatial centroid shifted from the center to the northeast, then to the southwest, and finally returned to the center. The distribution is shaped by the synergistic interaction of multiple factors: railway networks exert the strongest influence, natural conditions provide fundamental constraints, cultural factors play a reinforcing role, and historical development and policy orientation act as regulatory forces. Region-specific strategies are proposed to guide the conservation and sustainable transformation of industrial heritage in old industrial cities.

IntroductionCognitive impairment is a debilitating manifestation in Parkinson’s disease (PD). We sought to investigate predictors of PD-CI (PD with cognitive impairment).MethodsWe systematically searched PubMed and Cochrane Library for prospective cohort studies and pooled estimates via random-effects models. Primary analyses for all types of cognitive impairments and subgroup analyses by separate outcomes were conducted.ResultsA total of 28,009 studies were identified, of which 57 studies with 31 factors were included in the meta-analysis. In the primary analysis, 13 factors were associated with PD-CI, comprising advanced age [relative risk (RR) = 1.07, 95% confidence interval (CI) = 1.03–1.12], age at onset (RR = 4.43, 95% CI = 1.87–10.54), postural-instability-gait disorder (RR = 3.76, 95% CI = 1.36–10.40), higher Hoehn and Yahr stage (RR = 1.83, 95% CI = 1.35–2.47), higher UPDRS III score (RR = 1.04, 95% CI = 1.01–1.08), rapid eye movement sleep behavior disorder (RR = 3.72, 95% CI = 1.20–11.54), hallucinations (RR = 3.09, 95% CI = 1.61–5.93), orthostatic hypotension (RR = 2.98, 95% CI = 1.41–6.28), anxiety (RR = 2.59, 95% CI = 1.18–5.68), APOE ε2 (RR = 6.47, 95% CI = 1.29–32.53), APOE ε4 (RR = 3.04, 95% CI = 1.88–4.91), electroencephalogram theta power > median (RR = 2.93, 95% CI = 1.61–5.33), and alpha power < median (RR = 1.77, 95% CI = 1.07–2.92). In the subgroup analysis, MAPT H1/H1 genotype increased the risk of dementia in PD. Sixty-four studies were included in the systematic review, of which 12 factors were additionally correlated with PD-CI using single studies.ConclusionsAdvanced age, genetic variation in APOE and MAPT, gait disturbance, motor assessments, non-motor symptoms, and electroencephalogram may be promising predictors for PD-CI.

The present study focuses on changes in synoptic-scale waves (SSWs) over the northwest Pacific (NWP) during boreal summer and compares them with intraseasonal oscillations (ISOs). The results show that the intensity of eddy kinetic energy (EKE)-based SSWs (2–10-day period) has greater climatological means and interannual variations than the 10–20-day and 30–60-day ISOs. Additionally, the distribution of the SSWs is similar to that of the 10–20-day ISO, which shows a greater amplitude in the monsoon trough region. Further investigation reveals that the EKE-based SSW intensity over the South China Sea-tropical NWP region, where the greatest SSW activity occurs, is positively correlated with central Pacific (CP) warming. The EKE-based SSW intensity tends to be higher in years of developing CP warming. The influences of the Indian Ocean sea surface temperature (SST) are limited and show a weak correlation with the EKE-based SSW intensity over the key region (5° N–20° N, 115° E–155° E). In turn, the SSWs have impacts on local SST anomalies, with active SSWs leading to SST cooling. CP warming induces a favorable environment for SSW origination over CP and SSW development in the monsoon trough region. Concurrent with the CP warming-associated easterly vertical wind shear, upward vertical motion and abundant moisture supply, significant synoptic-scale EKE conversion occurs over the key region, which indicates its dominant role in influencing the SSW intensity. The influences of CP warming on SSW intensity over the NWP demonstrate the potential of the El Niño Modoki index for predicting interannual variations in SSW intensity. Moreover, considering that influences related to SSWs bear a resemblance to the 10–20-day ISOs, future research should take into account the contributions of SSWs to avoid overestimating the impact from ISOs.