Automatically detecting OSAHS patients based on transfer learning and model fusion.

Objective. Snoring is the most typical symptom of obstructive sleep apnea hypopnea syndrome (OSAHS) that can be used to develop a non-invasive approach for automatically detecting OSAHS patients.Approach. In this work, a model based on transfer learning and model fusion was applied to classify simple snorers and OSAHS patients. Three kinds of basic models were constructed based on pretrained Visual Geometry Group-16 (VGG16), pretrained audio neural networks (PANN), and Mel-frequency cepstral coefficient (MFCC). The XGBoost was used to select features based on feature importance, the majority voting strategy was applied to fuse these basic models and leave-one-subject-out cross validation was used to evaluate the proposed model.Main results. The results show that the fused model embedded with top-5 VGG16 features, top-5 PANN features, and MFCC feature can correctly identify OSAHS patients (AHI > 5) with 100% accuracy.Significance. The proposed fused model provides a good classification performance with lower computational cost and higher robustness that makes detecting OSAHS patients at home possible.

REDUCED CHLOROPLAST COVERAGE proteins are required for plastid proliferation and carotenoid accumulation in tomato.

Increasing the amount of cellular space allocated to plastids will lead to increases in the quality and yield of crop plants. However, mechanisms that allocate cellular space to plastids remain poorly understood. To test whether the tomato (Solanum lycopersicum L.) REDUCED CHLOROPLAST COVERAGE (SlREC) gene products serve as central components of the mechanism that allocates cellular space to plastids and contribute to the quality of tomato fruit, we knocked out the four-member SlREC gene family. We found that slrec mutants accumulated lower levels of chlorophyll in leaves and fruit, accumulated lower levels of carotenoids in flowers and fruits, allocated less cellular space to plastids in leaf mesophyll and fruit pericarp cells, and developed abnormal plastids in flowers and fruits. Fruit produced by slrec mutants initiated ripening later than wild type and produced abnormal levels of ethylene and ABA. Metabolome and transcriptome analyses of slrec mutant fruit indicated that the SlREC gene products markedly influence plastid-related gene expression, primary and specialized metabolism, and the response to biotic stress. Our findings and previous work with distinct species indicate that REC proteins help allocate cellular space to plastids in diverse species and cell types and, thus, play a central role in allocating cellular space to plastids. Moreover, the SlREC proteins are required for the high-level accumulation of chlorophyll and carotenoids in diverse organs, including fruit, promote the development of plastids, and influence fruit ripening by acting both upstream and downstream of ABA biosynthesis in a complex network.

scGAL: unmask tumor clonal substructure by jointly analyzing independent single-cell copy number and scRNA-seq data.

BACKGROUND: Accurately deciphering clonal copy number substructure can provide insights into the evolutionary mechanism of cancer, and clustering single-cell copy number profiles has become an effective means to unmask intra-tumor heterogeneity (ITH). However, copy numbers inferred from single-cell DNA sequencing (scDNA-seq) data are error-prone due to technically confounding factors such as amplification bias and allele-dropout, and this makes it difficult to precisely identify the ITH. RESULTS: We introduce a hybrid model called scGAL to infer clonal copy number substructure. It combines an autoencoder with a generative adversarial network to jointly analyze independent single-cell copy number profiles and gene expression data from same cell line. Under an adversarial learning framework, scGAL exploits complementary information from gene expression data to relieve the effects of noise in copy number data, and learns latent representations of scDNA-seq cells for accurate inference of the ITH. Evaluation results on three real cancer datasets suggest scGAL is able to accurately infer clonal architecture and surpasses other similar methods. In addition, assessment of scGAL on various simulated datasets demonstrates its high robustness against the changes of data size and distribution. scGAL can be accessed at: https://github.com/zhyu-lab/scgal . CONCLUSIONS: Joint analysis of independent single-cell copy number and gene expression data from a same cell line can effectively exploit complementary information from individual omics, and thus gives more refined indication of clonal copy number substructure.

Effects of purple potato anthocyanins on the in vitro digestive properties of starches of different crystalline types.

This study explored the potential of purple potato anthocyanins (PPAs) in regulating the digestive properties of starches of various crystalline types. In vitro digestion experiments indicated that PPAs inhibit the hydrolysis of rice starch (A-type) better than that of garden pea starch (C-type) and potato starch (B-type). Further structural assessment of different PPA-starch systems showed that PPAs and starch likely interact through non-covalent bonds, resulting in structural changes. Microstructural changes observed in the starches were consistent with the in vitro digestion results, and the chain length and proportions of short/long chains in amylopectin molecules affected the binding strengths and interaction modes between PPAs and starch. Hence, the three starches differed in their PPA loading efficiency and digestibility. These discoveries contribute to a deeper understanding of the mechanisms underlying the inhibition of starch digestibility by PPAs. They can aid the formulation of value-added products and low-glycemic-index foods.

Organocatalytic enantioselective synthesis of Csp2-N atropisomers via formal Csp2-O bond amination.

Compared with well-developed construction of Csp2-Csp2 atropisomers, the synthesis of Csp2-N atropisomers remains in its infancy, which is recognized as both appealing and challenging. Herein, we achieved the first organocatalyzed asymmetric synthesis of Csp2-N atropisomers by formal Csp2-O amination. With the aid of a suitable acid, 3-alkynyl-3-hydroxyisoindolinones reacted smoothly with 1-methylnaphthalen-2-ols to afford a wide range of atropisomers by selective formation of the Csp2-N axis. Particularly, both the kinetic (Z)-products and the thermodynamic (E)-products could be selectively formed. Furthermore, the rarely used combination of two chiral Brønsted acid catalysts achieved excellent enantiocontrol, which is intriguing and unusual in organocatalysis. Based on control experiments and DFT calculations, a cascade dehydration/addition/rearrangement process was proposed. More importantly, this work provided a new plat-form for direct atroposelective construction of the chiral Csp2-N axis.

Corrigendum: Optimizing window size and directional parameters of GLCM texture features for estimating rice AGB based on UAVs multispectral imagery.

[This corrects the article DOI: 10.3389/fpls.2023.1284235.].

sscNOVA: a semi-supervised convolutional neural network for predicting functional regulatory variants in autoimmune diseases.

Genome-wide association studies (GWAS) have identified thousands of variants in the human genome with autoimmune diseases. However, identifying functional regulatory variants associated with autoimmune diseases remains challenging, largely because of insufficient experimental validation data. We adopt the concept of semi-supervised learning by combining labeled and unlabeled data to develop a deep learning-based algorithm framework, sscNOVA, to predict functional regulatory variants in autoimmune diseases and analyze the functional characteristics of these regulatory variants. Compared to traditional supervised learning methods, our approach leverages more variants' data to explore the relationship between functional regulatory variants and autoimmune diseases. Based on the experimentally curated testing dataset and evaluation metrics, we find that sscNOVA outperforms other state-of-the-art methods. Furthermore, we illustrate that sscNOVA can help to improve the prioritization of functional regulatory variants from lead single-nucleotide polymorphisms and the proxy variants in autoimmune GWAS data.

Association of high-density lipoprotein cholesterol with all-cause and cause-specific mortality in a Chinese population of 3.3 million adults: a prospective cohort study.

Background: High-density lipoprotein cholesterol (HDL-C) has been inversely associated with cardiovascular disease (CVD) risk, but recent evidence suggests that extremely high levels of HDL-C are paradoxically related to increased CVD incidence and mortality. This study aimed to comprehensively examine the associations of HDL-C with all-cause and cause-specific mortality in a Chinese population. Methods: The China Health Evaluation And risk Reduction through nationwide Teamwork (ChinaHEART) project included 3,397,547 participants aged 35-75 years with a median follow-up of 3.9 years. Baseline HDL-C levels were measured, and mortality data was ascertained from the National Mortality Surveillance System and Vital Registration of Chinese Center for Disease Control and Prevention. Findings: This study found U-shaped associations of HDL-C with all-cause, cardiovascular and cancer mortality. When compared with the groups with the lowest risk, the adjusted hazard ratios (95% CIs) for HDL-C <30 mg/dL was 1.23 (1.17-1.29), 1.33 (1.23-1.45) and 1.18 (1.09-1.28) for all-cause, CVD and cancer mortality, respectively. For HDL-C >90 mg/dL, the corresponding HR (95% CIs) was 1.10 (1.05-1.15), 1.09 (1.01-1.18) and 1.11 (1.03-1.19). Similar U-shaped patterns were also found in associations of HDL-C with ischemic heart disease, ischemic stroke, and liver cancer. About 3.25% of all-cause mortality could be attributed to abnormal levels of HDL-C. The major contributor to mortality was ischemic heart disease (16.06 deaths per 100,000 persons, 95% UI: 10.30-22.67) for HDL-C <40 mg/dL and esophageal cancer (2.29 deaths per 100,000 persons, 95% UI: 0.57-4.77) for HDL-C >70 mg/dL. Interpretation: Both low and high HDL-C were associated with increased mortality risk. We recommended 50-79 mg/dL as the optimal range of HDL-C among Chinese adults. Individuals with dyslipidemia might benefit from proper management of both low and high HDL-C. Funding: The CAMS Innovation Fund for Medical Science (2021-1-I2M-011), the National High Level Hospital Clinical Research Funding (2022-GSP-GG-4), the Ministry of Finance of China and National Health Commission of China, and the 111 Project from the Ministry of Education of China (B16005), the Program for Guangdong Introducing Innovative and Enterpreneurial Teams (2019ZT08Y481), Sanming Project of Medicine in Shenzhen (SZSM201811096), the Young Talent Program of the Academician Fund, Fuwai Hospital Chinese Academy of Medical Sciences, Shenzhen (YS-2022-006) and Guangdong Basic and Applied Basic Research Foundation (2023A1515010076 & 2021A1515220173).

[Tetramethylpyrazine regulates angiogenesis of endothelial cells in cerebral ischemic stroke injury via SIRT1/VEGFA signaling pathway].

This study aims to investigate whether tetramethylpyrazine(TMP) can stimulate angiogenesis in cerebral microvascular endothelial cells and alleviate cerebral ischemic stroke(CIS) and to explore the underlying mechanisms. In the animal study, adult Sprague-Dawley rats(n=15) were assigned into sham surgery(sham), middle cerebral artery occlusion/reperfusion(MCAO/R), and MCAO/R+TMP(intraperitoneal injection of 20 mg·kg~(-1)) groups. The neurological function was evaluated by the Z-Longa method. The cerebral infarction volume was detected by TTC staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the expression of vascular endothelial growth factor(VEGF), angiopoietin(Ang), and platelet-derived growth factor(PDGF). Immunofluorescence staining was employed to detect Ki67 and the expression of vascular endothelial growth factor A(VEGFA) and slient information regulator 1(SIRT1). Western blot was employed to determine the expression levels of VEGFA, SIRT1, angiopoietin-2(Ang-2), and platelet-derived growth factor B(PDGFB). In the cell study, mouse brain-derived endothelial cells(Bend.3) were cultured, and the optimal concentration of TMP was determined. Then, VEGF, Ang, and PDGF were detected by ELISA after the addition of cabozantinib. Western blot was employed to measure the expression of VEGFA, Ang-2, and PDGFB. Immunofluorescence staining was used to detect CD31, CD34, and Ki67, and the proliferation, migration, and tube formation ability of Bend.3 cells were observed in vitro. Western blot and immunofluorescence staining were performed to measure the expression of SIRT1 and VEGFA after addition of the SIRT1-specific inhibitor selisistat(EX-527). The results showed that compared with the sham group, the MCAO/R group had severe neurological function damage, increased infarction volume, up-regulated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, and PDGFB, and down-regulated expression of Ki67 and SIRT1(P<0.01). Compared with the MCAO/R group, the MCAO/R+TMP group presented alleviated neurological function damage, reduced infarction volume, and activated expression of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, Ki67, and SIRT1(P<0.01). The cell experiments showed that compared with the normal group, Bend.3 cells were activated by oxygen glucose deprivation/reoxygenation(OGD/R) treatment(P<0.05, P<0.01). Compared with the OGD/R group, the OGD/R+TMP group upregulated the expression levels of VEGF, VEGFA, Ang, Ang-2, PDGF, PDGFB, SIRT1, Ki67, CD31, and CD34, enhanced the angiogenic ability of Bend.3 cells without being inhibited by BMS or EX-527(P<0.05, P<0.01, P<0.001). The results suggest that TMP can activate the SIRT1/VEGFA signaling pathway to stimulate angiogenesis and alleviate CIS injury.

Healthy lifestyle, statin, and mortality in people with high CVD risk: A nationwide population-based cohort study.

Objective: To examine the joint association of healthy lifestyles and statin use with all-cause and cardiovascular mortality in high-risk individuals, and evaluate the survival benefits by life expectancy. Methods: During 2015-2021, participants aged 35-75 years were recruited by the China Health Evaluation And risk Reduction through nationwide Teamwork. Based on number of healthy lifestyles related to smoking, alcohol drinking, physical activity, and diet, we categorized them into: very healthy (3-4), healthy (2), and unhealthy (0-1). Statin use was determined by self-report taking statin in last two weeks. Results: Among the 265,209 included participants at high risk, 6979 deaths were observed, including 3236 CVD deaths during a median 3.6 years of follow-up. Individuals taking statin and with a very healthy lifestyle had the lowest risk of all-cause (HR: 0.70; 95 %CI: 0.57-0.87) and cardiovascular mortality (0.56; 0.40-0.79), compared with statin non-users with an unhealthy lifestyle. High-risk participants taking statin and with a very healthy lifestyle had the highest years of life gained (5.90 years at 35-year-old [4.14-7.67; P < 0.001]) compared with statin non-users with an unhealthy lifestyle among high-risk people. And their life expectancy was comparable with those without high risk but with a very healthy lifestyle (4.49 vs. 4.68 years). Conclusion: The combination of preventive medication and multiple healthy lifestyles was associated with lower risk of all-cause and cardiovascular mortality and largest survival benefits. Integrated strategy to improve long-term health for high-risk people was urgently needed.

Priming and Combined Strategies for the Application of Mesenchymal Stem Cells in Ischemic Stroke: A Promising Approach.

Ischemic stroke (IS) is a leading cause of death and disability worldwide. Tissue plasminogen activator (tPA) administration and mechanical thrombectomy are the main treatments but have a narrow time window. Mesenchymal stem cells (MSCs), which are easily scalable in vitro and lack ethical concerns, possess the potential to differentiate into various types of cells and secrete a great number of growth factors for neuroprotection and regeneration. Moreover, MSCs have low immunogenicity and tumorigenic properties, showing safety and preliminary efficacy both in preclinical studies and clinical trials of IS. However, it is unlikely that MSC treatment alone will be sufficient to maximize recovery due to the low survival rate of transplanted cells and various mechanisms of ischemic brain damage in the different stages of IS. Preconditioning was used to facilitate the homing, survival, and secretion ability of the grafted MSCs in the ischemic region, while combination therapies are alternatives that can maximize the treatment effects, focusing on multiple therapeutic targets to promote stroke recovery. In this case, the combination therapy can yield a synergistic effect. In this review, we summarize the type of MSCs, preconditioning methods, and combined strategies as well as their therapeutic mechanism in the treatment of IS to accelerate the transformation from basic research to clinical application.

Mild Stereoselective Synthesis of Densely Substituted [3]Dendralenes via Ru-Catalyzed Intermolecular Dimerization of 1,1-Disubstituted Allenes.

Described here is a mild and stereoselective protocol for the synthesis of [3]dendralenes via the intermolecular dimerization of allenes. With the proper choice of a ruthenium catalyst, a range of unactivated 1,1-disubstituted allenes, without prefunctionalization in the allylic position, reacted efficiently to provide rapid access to densely substituted [3]dendralenes. An intermolecular C-C bond and three different types of C═C double bonds (di-, tri-, and tetrasubstituted) embedded in an acyclic structure were constructed with good to high E/Z stereocontrol. This is in contrast to the known catalytic protocols that focus on allenes with prefunctionalization at the allylic position and/or monosubstituted allenes, which would proceed by a different mechanism or require less stereocontrol. The silyl-substituted dendralene products are precursors of other useful dendralene molecules. Density functional theory (DFT) studies and control experiments supported a mechanism involving oxidative cyclometalation, ß-H elimination (the rate-determining step), and reductive elimination.

Exploring Research Trend and Hotspots on Oxidative Stress in Ischemic Stroke (2001-2022): Insights from Bibliometric.

Oxidative stress is widely involved in the pathological process of ischemic stroke and ischemia-reperfusion. Several research have demonstrated that eliminating or reducing oxidative stress can alleviate the pathological changes of ischemic stroke. However, current clinical antioxidant treatment did not always perform as expected. This bibliometric research aims to identify research trends, topics, hotspots, and evolution on oxidative stress in the field of ischemic stroke, and to find potentially antioxidant strategies in future clinical treatment. Relevant publications were searched from the Web of Science (WOS) Core Collection databases (2001-2022). VOSviewer was used to visualize and analyze the development trends and hotspots. In the field of oxidative stress and ischemic stroke, the number of publications increased significantly from 2001 to 2022. China and the USA were the leading countries for publication output. The most prolific institutions were Stanford University. Journal of Cerebral Blood Flow and Metabolism and Stroke were the most cited journals. The research topics in this field include inflammation with oxidative stress, mitochondrial damage with oxidative stress, oxidative stress in reperfusion injury, oxidative stress in cognitive impairment and basic research and clinical translation of oxidative stress. Moreover, "NLRP3 inflammasome," "autophagy," "mitophagy," "miRNA," "ferroptosis," and "signaling pathway" are the emerging research hotspots in recent years. At present, multi-target regulation focusing on multi-mechanism crosstalk has progressed across this period, while challenges come from the transformation of basic research to clinical application. New detection technology and new nanomaterials are expected to integrate oxidative stress into the clinical treatment of ischemic stroke better.

Bibliometric Analysis of Stem Cells in Ischemic Stroke (2001-2022): Trends, Hotspots and Prospects.

Background: Ischemic stroke is a common cerebrovascular accident with a high risk of neurological deficits. Stem cell therapy has progressively attracted the interest of scientists and clinicians due to the benefits of promoting neural regeneration and regulating the microenvironment surrounding the lesion after ischemic stroke. Our study aimed to evaluate the development trends and research hotspots in the field of stem cells and ischemic stroke. Materials and methods: Publications related to stem cells and ischemic stroke were retrieved from the Web of Science from 2001 to 2022. Data analysis and mapping were performed using VOSviewer, Citespace and ImageGP. Results: In total, 1932 papers were included in the analysis. Publications have steadily increased over the past 22 years. China has contributed the maximum number of publications, whereas the USA ranked first in the total number of citations and was considered the center of the international collaboration network. University of South Florida, Henry Ford Hospital, and Oakland University were the most influential institutions. Stroke, Brain Research, and Neural Regeneration Research were the most productive journals. The research in this field was primarily focused on the effects of stem cells on neurogenesis, inflammation, and angiogenesis following ischemic stroke, as well as their therapeutic potential for the disease. In addition, neural stem cells and mesenchymal stem cells are the most commonly utilized stem cells. The topics related to miRNA, extracellular vesicles, exosomes, mesenchymal stem cells, neuroinflammation, and autophagy are current research hotspots. Conclusion: Our bibliometric study provides a novel perspective on the research trends in the field of stem cells and ischemic stroke. The outcome of this study may benefit scientists to identify research hotspots and development directions, thereby advancing the application of stem cell-based therapy for ischemic stroke.

Icariin ameliorates the cuprizone-induced demyelination associated with antioxidation and anti-inflammation.

The treatment of immunomodulation in multiple sclerosis (MS) can alleviate the severity and relapses. However, it cannot improve the neurological disability of patients due to a lack of myelin protection and regeneration. Therefore, remyelinating therapies may be one of the feasible strategies that can prevent axonal degeneration and restore neurological disability. Natural product icariin (ICA) is a flavonol compound extracted from epimedium flavonoids, which has neuroprotective effects in several models of neurological diseases. Here, we attempt to explore whether ICA has the potential to treat demyelination and its possible mechanisms of action using lipopolysaccharide-treated BV2 microglia, primary microglia, bone marrow-derived macrophages, and cuprizone-induced demyelination model. The indicators of oxidative stress and inflammatory response were evaluated using commercial kits. The results showed that ICA significantly reduced the levels of oxidative intermediates nitric oxide, hydrogen peroxide, malondialdehyde, and inflammatory cytokines TNF-α, IL-1ß, and increased the levels of antioxidants superoxide dismutase, catalase, glutathione peroxidase, and anti-inflammatory cytokines IL-10 and TGF-ß in vitro cell experiments. In vivo demyelination model, ICA significantly alleviated the behavioral abnormalities and enhanced the integrated optical density/mm2 of Black Gold II and myelin basic protein myelin staining, accompanied by the inhibition of oxidative stress/inflammatory response. Immunohistochemical staining showed that ICA significantly induced the expression of nuclear factor erythroid derived 2/heme oxygenase-1 (Nrf2/HO-1) and inhibited the expression of toll-like receptor 4/ nuclear factor kappa B (TLR4/NF-κB), which are two key signaling pathways in antioxidant and anti-inflammatory processes. Our results strongly suggest that ICA may be used as a potential agent to treat demyelination via regulating Nrf2/HO-1-mediated antioxidative stress and TLR4/NF-κB-mediated inflammatory responses.

Associations between Chinese visceral adiposity index and risks of all-cause and cause-specific mortality: A population-based cohort study.

AIM: To determine the associations between the Chinese visceral adiposity index (CVAI) and the risks of all-cause and cause-specific mortality. MATERIALS AND METHODS: A total of 3 916 214 Chinese adults were enrolled in a nationwide population cohort covering all 31 provinces of mainland China. The CVAI was calculated based on age, body mass index, waist circumference, and triglyceride and high-density lipoprotein cholesterol concentrations. We used a Cox proportional hazards regression model to determine the hazard ratios and 95% confidence intervals (CIs) for risk of mortality associated with different CVAI levels. RESULTS: The median follow-up duration was 3.8 years. A total of 86 158 deaths (34 867 cardiovascular disease [CVD] deaths, 29 884 cancer deaths, and 21 407 deaths due to other causes) were identified. In general, after adjusting for potential confounding factors, a U-shaped relationship between CVAI and all-cause mortality was observed by restricted cubic spline (RCS). Compared with participants in CVAI quartile 1, those in CVAI quartile 4 had a 23.0% (95% CI 20.0%-25.0%) lower risk of cancer death, but a 23.0% (95% CI 19.0-27.0) higher risk of CVD death. In subgroup analysis, a J-shaped and inverted U-shaped relationship for all-cause mortality and cancer mortality was observed in the group aged < 60 years. CONCLUSIONS: The CVAI, an accessible indicator reflecting visceral obesity among Chinese adults, has predictive value for all-cause, CVD, and cancer mortality risks. Moreover, the CVAI carries significance in the field of health economics and secondary prevention. In the future, it could be used for early screening purposes.

Identification of OSAHS patients based on ReliefF-mRMR feature selection.

Obstructive Sleep Apnea Hypopnea Syndrome (OSAHS) is a serious chronic sleep disorder. Snoring is a common and easily observable symptom of OSAHS patients. The purpose of this work is to identify OSAHS patients by analyzing the acoustic characteristics of snoring sounds throughout the entire night. Ten types of acoustic features, such as Mel-frequency cepstral coefficients (MFCC), linear prediction coefficients (LPC) and spectral entropy among others, were extracted from the snoring sounds. A fused feature selection algorithm based on ReliefF and Max-Relevance and Min-Redundancy (mRMR) was proposed for optimal feature set selection. Four types of machine learning models were then applied to validate the effectiveness of OSAHS patient identification. The results show that the proposed feature selection algorithm can effectively select features with high contribution, including MFCC and LPC. Based on the selected top-20 features and using a support vector machine model, the accuracies in identifying OSAHS patients under the thresholds of AHI = 5,15, and 30, were 100%, 100%, and 98.94%, respectively. This indicates that the proposed model can effectively identify OSAHS patients.

Associations of remnant cholesterol with cardiovascular and cancer mortality in a nationwide cohort.

The health significance of triglyceride-rich lipoproteins, also known as remnant cholesterol, has been increasingly recognized. However, evidence of their associations with cause-specific mortality in the general population was previously insufficient. To explore these associations and their heterogeneities across subgroups, a prospective cohort study was conducted including 3,403,414 community-based participants from ChinaHEART, an ongoing government-funded public health program throughout China, from November 2014 through December 2022. The study assessed mortality risk of all-cause mortality, cardiovascular disease (CVD) mortality (including mortality from ischemic heart diseases (IHD), ischemic stroke (IS), and hemorrhagic stroke (HS), separately), and cancer mortality (including lung cancer, stomach cancer, and liver cancer, separately). During the 4-year follow-up, 23,646 individuals died from CVD (including 8807 from IHD, 3067 from IS, and 5190 from HS), and 20,318 from cancer (including 6208 from lung cancer, 3013 from liver cancer, and 2174 from stomach cancer). Compared with individuals with remnant cholesterol <17.9 mg/dL, multivariable-adjusted mortality hazard ratios (HRs) for individuals with remnant cholesterol ≥27.7 mg/dL were 1.03 (1.00-1.05) for all-cause mortality, 1.17 (1.12-1.21) for CVD (1.19 (1.12-1.27) for IHD mortality, and 1.22 (1.09-1.36) for IS mortality), and 0.90 (0.87-0.94) for all-cancer mortality (0.94 (0.87-1.02) for lung cancer, 0.59 (0.53-0.66) for liver cancer, and 0.73 (0.64-0.83) for stomach cancer). In summary, this study revealed a correlation between increased remnant cholesterol levels and an elevated risk of cardiovascular disease mortality, as well as a reduced risk of mortality for certain types of cancer.

[Eriodictyol improves cognitive function in 5×FAD mice of Alzheimer's disease by inhibiting the microglia NLRP3 inflammasome signaling pathway].

Objective To investigate the therapeutic effects of eriodictyol on transgenic mice with five familial Alzheimer's disease (5×FAD) and the modulation of NOD-like receptor-pyrin domain containing 3 (NLRP3) inflammasome in microglia. Methods The 8-month-old 5×FAD mice were randomly divided into AD model group and eriodictyol-treated AD group. Same-aged wild-type C57BL/6J mice were randomly divided into wild-type (WT) control group and eriodictyol-treated WT group. Morris water maze and Y-maze experiments were performed to assess the cognitive function of each group of mice. Immunofluorescence histochemical staining was performed to detect the expression of NLRP3, caspase-1 and interleukin 18 (IL-18) in mouse brain tissue, and Western blot was performed to detect the protein levels of NLRP3, apoptosis-associated speckle-like protein containing a CARD (ASC), caspase-1, IL-18, IL-1ß and ion calcium-binding adaptor molecule 1 (Iba-1) in mouse brain tissue. Results Compared with the WT group and the eriodictyol-treated WT group, cognitive function was significantly impaired in the AD group mice, and the expression of NLRP3, caspase-1, IL-18, ASC, IL-1ß and Iba1 were increased in microglia of mouse brain tissue. After eriodictyol treatment, learning memory and cognitive function were improved, and the expression of NLRP3, ASC, caspase-1, IL-1ß, IL-18 and Iba1 were all down-regulated in the eriodictyol-treated AD group mice compared with the AD group mice. Conclusion Eriodictyol may improve cognitive function in animal models of AD by inhibiting the activation of the NLRP3 signaling pathway in microglia.

Astragaloside IV inhibits experimental autoimmune encephalomyelitis by modulating the polarization of both microglia/macrophages and astrocytes.

Astragaloside IV (AST IV), a major saponin component and active ingredient isolated from Astragalus membranaceus, has been well known to exhibit neuroprotective effects on diverse models of neurological diseases. Accumulating evidence suggests that dynamic balance of microglia/macrophages and astrocytes plays a vital role in neuroprotection and remyelination. However, dysregulation of microglia/macrophages and astrocytes orchestrate the pathogenesis of nervous system disorders. Therefore, we hypothesized that switching the transformation of microglia/macrophages and astrocytes into the neuroprotective M2 and A2 phenotypes, respectively, could be a potential target for therapeutic intervention. In the present study, we evaluate the efficacy of AST IV intervention on the effects of microglia/macrophages and astrocytes in an experimental autoimmune encephalomyelitis (EAE) model. AST IV improved paralysis and pathology of EAE by inhibiting the neurotoxic M1 microglia/macrophage phenotype, promoting M2 phenotype, shifting astrocytes towards a neuroprotective A2 phenotype, and protecting neurons from apoptosis through inhibition of TLR4/Myd88/NF-kB signalling pathway. Our study showed that AST IV could be a potential and promising drug for multiple sclerosis treatment.