Altered morphometric similarity networks in insomnia disorder.

Previous studies on structural covariance network (SCN) suggested that patients with insomnia disorder (ID) show abnormal structural connectivity, primarily affecting the somatomotor network (SMN) and default mode network (DMN). However, evaluating a single structural index in SCN can only reveal direct covariance relationship between two brain regions, failing to uncover synergistic changes in multiple structural features. To cover this research gap, the present study utilized novel morphometric similarity networks (MSN) to examine the morphometric similarity between cortical areas in terms of multiple sMRI parameters measured at each area. With seven T1-weighted imaging morphometric features from the Desikan-Killiany atlas, individual MSN was constructed for patients with ID (N = 87) and healthy control groups (HCs, N = 84). Two-sample t-test revealed differences in MSN between patients with ID and HCs. Correlation analyses examined associations between MSNs and sleep quality, insomnia symptom severity, and depressive symptoms severity in patients with ID. The right paracentral lobule (PCL) exhibited decreased morphometric similarity in patients with ID compared to HCs, mainly manifested by its de-differentiation (meaning loss of distinctiveness) with the SMN, DMN, and ventral attention network (VAN), as well as its decoupling with the visual network (VN). Greater PCL-based de-differentiation correlated with less severe insomnia and fewer depressive symptoms in the patients group. Additionally, patients with less depressive symptoms showed greater PCL de-differentiation from the SMN. As an important pilot step in revealing the underlying morphometric similarity alterations in insomnia disorder, the present study identified the right PCL as a hub region that is de-differentiated with other high-order networks. Our study also revealed that MSN has an important potential to capture clinical significance related to insomnia disorder.

Highly Effective Nobiletin-MPN in Yeast Microcapsules for Targeted Modulation of Oxidative Stress, NLRP3 Inflammasome Activation, and Immune Responses in Ulcerative Colitis.

Inflammatory bowel disease (IBD) etiology is intricately linked to oxidative stress and inflammasome activation. Natural antioxidant nobiletin (NOB) contains excellent anti-inflammatory properties in alleviating intestinal injury. However, the insufficient water solubility and low bioavailability restrict its oral intervention for IBD. Herein, we constructed a highly efficient NOB-loaded yeast microcapsule (YM, NEFY) exhibiting marked therapeutic efficacy for dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) at a low oral dose of NOB (20 mg/kg). We utilized the metal polyphenol network (MPN) formed by self-assembly of epigallocatechin gallate (EGCG) and FeCl3 as the intermediate carrier to improve the encapsulation efficiency (EE) of NOB by 4.2 times. These microcapsules effectively alleviated the inflammatory reaction and oxidative stress of RAW264.7 macrophages induced by lipopolysaccharide (LPS). In vivo, NEFY with biocompatibility enabled the intestinal enrichment of NOB through controlled gastrointestinal release and macrophage targeting. In addition, NEFY could inhibit NLRP3 inflammasome and balance the macrophage polarization, which favors the complete intestinal mucosal barrier and recovery of colitis. Based on the oral targeted delivery platform of YM, this work proposes a novel strategy for developing and utilizing the natural flavone NOB to intervene in intestinal inflammation-related diseases.

Digestive and Absorptive Properties of the Antarctic Krill Tripeptide Phe-Pro-Phe (FPF) and Its Auxiliary Memory-Enhancing Effect.

Aging and stress have contributed to the development of memory disorders. Phe-Pro-Phe (FPF) was identified with high stability by mass spectrometry from simulated gastrointestinal digestion and everted gut sac products of the Antarctic krill peptide Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR) which was found to have a positive impact on memory enhancement. This study investigated the digestive stability, absorption, and memory-enhancing effects of FPF using nuclear magnetic resonance spectroscopy, simulated gastrointestinal digestion, in vivo fluorescence distribution analysis, mouse behavioral experiments, acetylcholine function, Nissl staining, immunofluorescence, and immunohistochemistry. FPF crossed the blood-brain barrier into the brain after digestion, significantly reduced shock time, working memory errors, and reference memory errors, and increased the recognition index. Additionally, FPF elevated ACh content; Nissl body counts; and CREB, SYN, and PSD-95 expression levels, while reducing AChE activity (P < 0.05). This implies that FPF prevents scopolamine-induced memory impairment and provides a basis for future research on memory disorders.

A Novel Tetrapeptide Ala-Phe-Phe-Pro (AFFP) Derived from Antarctic Krill Prevents Scopolamine-Induced Memory Disorder by Balancing Lipid Metabolism of Mice Hippocampus.

Memory impairment is a serious problem with organismal aging and increased social pressure. The tetrapeptide Ala-Phe-Phe-Pro (AFFP) is a synthetic analogue of Antarctic krill derived from the memory-improving Antarctic krill peptide Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg (SSDAFFPFR) after digestion and absorption. The objective of this research was to assess the neuroprotective effects of AFFP by reducing oxidative stress and controlling lipid metabolism in the brains of mice with memory impairment caused by scopolamine. The 1H Nuclear magnetic resonance spectroscopy results showed that AFFP had three active hydrogen sites that could contribute to its antioxidant properties. The findings from in vivo tests demonstrated that AFFP greatly enhanced the mice's behavioral performance in the passive avoidance, novel object recognition, and eight-arm maze experiments. AFFP reduced oxidative stress by enhancing superoxide dismutase activity and malondialdehyde levels in mice serum, thereby decreasing reactive oxygen species level in the mice hippocampus. In addition, AFFP increased the unsaturated lipid content to balance the unsaturated lipid level against the neurotoxicity of the mice hippocampus. Our findings suggest that AFFP emerges as a potential dietary intervention for the prevention of memory impairment disorders.

Prophylactic and therapeutic inhalation of two essential oils ameliorates scopolamine-induced cognitive impairment in mice.

Clover and lemongrass essential oils of contrasting composition, at three concentration levels (1%, 5%, 10%), were administrated via prophylactic and therapeutic inhalation to scopolamine-treated mice. Chemical analysis showed that clover oil was dominant in eugenol (47.69%) and lemongrass free of eugenol but mainly containing monoterpenoids of comparable proportions. Animal behavioural and brain biochemical tests showed that injection of scopolamine caused memory and learning deficit in mice while prophylactic and therapeutic inhalation of two oils at moderate to high concentrations all obviously reversed the cognitive impairment via inhibiting acetylcholinesterase activities, oxidation and inflammation. Lemongrass essential oil with diverse monoterpenoids can be as effective as or a little bit more potent than eugenol-rich clover essential oil possibly due to the synergistic effect of various monoterpenoids. These findings implied that sniffing of such aroma recipes could be a promising complementary approach for the mitigation of Alzheimer's disease-related cognitive impairment.

Research progress on chitosan and its derivatives in the fields of corrosion inhibition and antimicrobial activity.

Chitosan stands out as the only known polysaccharide of its kind, second only to cellulose. As the second-largest biopolymer globally, chitosan and its derivatives are extensively used in diverse areas such as metal anti-corrosion prevention, food production, and medical fields. Its benefits include environmental friendliness, non-toxicity, cost-effectiveness, and biodegradability. Notably, the use of chitosan and its derivatives has gained substantial attention and has been extensively researched in the fields of metal anti-corrosion prevention and antibacterial applications. By means of chemical modification or synergistic action, the inherent limitations of chitosan can be substantially improved, thereby enhancing its biological and physicochemical properties to meet a wider range of applications and more demanding application requirements. This article offers a comprehensive review of chitosan and its modified composite materials, focusing on the enhancement of their anticorrosion and antibacterial properties, as well as the mechanisms by which they serve as anticorrosion and antibacterial agents. Additionally, it summarizes the synthesis routes of various modification methods of chitosan and their applications in different fields, aiming to contribute to the interdisciplinary development and potential applications of chitosan in various areas.

Sex-specific associations between haemoglobin glycation index and the risk of cardiovascular and all-cause mortality in individuals with pre-diabetes and diabetes: A large prospective cohort study.

AIM: The aim of this study was to investigate the relationship between the haemoglobin glycation index (HGI), and cardiovascular disease (CVD) and all-cause mortality in adults with pre-diabetes and diabetes. METHODS: This study included 10 267 adults with pre-diabetes and diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Sex-differentiated relationships between HGI and mortality were elucidated using multivariate Cox proportional hazards models, restricted cubic splines and a two-piecewise Cox proportional hazards model. RESULTS: During the median follow-up time of 103.5 months, a total of 535 CVD deaths and 1918 all-cause deaths were recorded. After multivariate adjustment, in males with pre-diabetes and diabetes, there was a U-shaped relationship between HGI and CVD mortality and all-cause mortality, with threshold points of -0.68 and -0.63, respectively. Before the threshold point, HGI was negatively associated with CVD mortality [hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.41, 0.89] and all-cause mortality (HR 0.56; 95% CI 0.43, 0.74), and after the threshold point, HGI was positively associated with CVD mortality (HR 1.46; 95% CI 1.23, 1.73) and all-cause mortality (HR 1.40; 95% CI 1.23, 1.59). In contrast, HGI had an L-shaped relationship with all-cause mortality and no significant association with CVD mortality in females. To the left of the threshold points, the risk of all-cause mortality decreased (HR 0.50; 95% CI 0.35, 0.71) progressively with increasing HGI. CONCLUSIONS: In the cohort study, HGI in pre-diabetic and diabetic populations was found to have a U-shaped association with CVD mortality and all-cause mortality in males and an L-shaped association with all-cause mortality only in females. Further prospective and mechanistic studies are warranted.

A feasibility study on indoor therapeutic horticulture to alleviate sleep and anxiety problems: The impact of plants and activity choice on its therapeutic effect.

INTRODUCTION: Therapeutic horticulture (TH) is increasingly being applied for sub-health or patient mental health care. Whether plant and activity type will affect TH's effectiveness is unclear. AIM: To evaluate the feasibility of an indoor TH for alleviating the anxiety symptoms and sleeping problems of people with poor sleep quality, and explore the potential affection of plant and activity type on health benefits. METHOD: Thirty subjects (all with sleep problems and half with anxiety problems) were randomly assigned to three groups to do horticultural activities with ornamental plants, general aromatic plants, or aromatic plants with reported mental health functions, respectively. Six indoor TH activities were then held sequentially within two weeks. Psychological scales, subjective feedback questionnaires, and physiological indicators were used as evaluation indexes before and after horticulture activities. RESULTS: The TH relieved subjects' sleep and anxiety problems and was particularly effective in alleviating anxiety among people with high anxiety levels. Using ornamental plants was more effective in relieving stress while functional aromatic plants performed better in sleep improvement and satisfaction to TH. Each horticultural activity could improve mood state but showed different effects on the vitality of the participants. CONCLUSION: The above findings provided some basis for the potential benefits of selecting plants and activities based on psychological care needs in the development of TH plans. Future research that expands upon the current project is warranted. A larger sample size is beneficial for obtaining more powerful statistical results.

Regulation mechanisms of sea cucumber peptides against scopolamine-induced memory disorder and novel memory-improving peptides identification.

Memory impairment affects cognition and information processing, and attention, leading to a decline in life quality of patients. Previous studies have shown the memory-improving effects of sea cucumber peptides. This study further explored the memory-improving mechanisms of sea cucumber peptides using scopolamine-induced memory-impaired mice and identified novel memory-improving peptides within low molecular weight peptide fractions. The sea cucumber peptides were categorized into three groups based on their molecular weights: SCP-L (molecular weight greater than 10 kDa), SCP-M (weight between 3 kDa and 10 kDa), and SCP-S (molecular weight less than 3 kDa). The results showed that SCP-S improved behavioral performance by regulating cholinergic system disorder and reducing oxidative stress levels, distinguishing itself from SCP-M and SCP-L. Further, SCP-S was found to exhibit a well ability in alleviating the degree of neuroinflammation dependent on microglia and promoting synaptic plasticity. Additionally, a novel memory-improving peptide Ser-Phe-Gly-Asp-Ile (SFGDI) was identified by EASY-nano-LC/MS/MS after simulated digestion-absorption coupling of in silico technologies from SCP-S. SFGDI protected against oxidative stress and regulated cholinergic system in scopolamine-induced PC12 cells. These findings suggest that SCP-S and SFGDI might be considered as potential memory-improving food for people suffering from memory disorders.

Response inhibition impairment related to altered frontal-striatal functional connectivity in insomnia disorder: A pilot and non-clinical study.

BACKGROUND: It is not clear whether and how insomnia disorder (ID) impairs response inhibition ability. Fronto-striatal functional connectivity (FC) plays a critical role in response inhibition and is found be abnormal in patients with ID. In this study, we examined whether insomnia symptoms impair response inhibition in a large non-clinical sample and whether impaired response inhibition is related to abnormal fronto-striatal FC. METHODS: One hundred and fifteen young ID patients and 160 age and sex-matched healthy controls (HC) underwent resting-state functional magnetic response imaging scans and performed the stop-signal task (SST). Performance of SST, Gray Matter Volumes (GMVs), and connections of brain regions related to fronto-striatal circuits was compared between groups. Further examined the association between response inhibition impairment and fronto-striatal FC. RESULTS: The behavioral results showed that patients with ID had significantly longer stop-signal reaction time (SSRT) compared with the HC, reflecting the impaired response inhibition among IDs. Brain imaging results showed IDs had decreased GMVs of the Right Superior Frontal (SFG) and left Supplementary Motor area (SMA). Seed-based FC results showed that compared to HC, the ID showed decreased FC between left SMA and left Paracentral lobule, left SMA and right SMA, and right SFG and right Orbital Middle Frontal gyrus, and increased FC between right SFG and right putamen. Meanwhile, the FC between right SFG and putamen was positively correlated with SSRT in IDs. CONCLUSIONS: The current study found significantly impaired response inhibition among ID and this impairment may be related to abnormal fronto-striatal FC in ID.

Dual Action of Reduced Allergenicity and Improved Memory of Instant Soybean Powder Hydrolysates.

Soy allergens are susceptible to inducing allergic reactions in infants and young animals, which have an impact on the effective daily utilization of proteins. In this study, we used Alcalase-hydrolyzed instant soybean powder (ISP) to clarify the sensitization changes of instant soybean powder hydrolysates (ISPH), and we explored the assisted memory-enhancing effects. BALB/c mice in the ISPH group showed significant improvement in the allergy symptoms, with their allergy symptom scores decreasing to (1.57 ± 0.53) and their specific serum IgE and IgG1 binding capacity decreasing by 28.00 and 25.73% (P < 0.05), which suppressed the mast cell degranulation rate. Meanwhile, the plasma HIS and IL-4 levels decreased by 12.59 and 25.32%, and the plasma INF-γ and IL- 10 levels increased by 30.64 and 27.79%, which obviously regulated the imbalance of Th1/Th2 cells and attenuated the tissue damage (P < 0.05). Furthermore, ISPH improved behavioral characteristics, increased cholinergic system activity, reduced neuronal cell damage or apoptosis, and increased the number of Nissl bodies to help improve memory in Kunming mice (P < 0.05). In general, alcalase-hydrolyzed ISP had the dual effects of reducing allergenicity and aiding in memory improvement.

M6A regulator methylation patterns and characteristics of immunity in acute ST-segment elevation myocardial infarction.

M6A methylation is the most prevalent and abundant RNA modification in mammals. Although there are many studies on the regulatory role of m6A methylation in the immune response, the m6A regulators in the pathogenesis of acute ST-segment elevation myocardial infarction (STEMI) remain unclear. We comprehensively analysed the role of m6A regulators in STEMI and built a predictive model, revealing the relationship between m6A methylations and the immune microenvironment. Differential analysis revealed that 18 of 24 m6A regulators were significantly differentially expressed, and there were substantial interactions between the m6A regulator. Then, we established a classifier and nomogram model based on 6 m6A regulators, which can easily distinguish the STEMI and control samples. Finally, two distinct m6A subtypes were obtained and significantly differentially expressed in terms of infiltrating immunocyte abundance, immune reaction activity and human leukocyte antigen genes. Three hub m6A phenotype related genes (RAC2, RELA, and WAS) in the midnightblue module were identified by weighted gene coexpression network analysis, and were associated with immunity. These findings suggest that m6A modification and the immune microenvironment play a key role in the pathogenesis of STEMI.

[Research progress on the effects of childhood obstructive sleep apnea syndrome on cognition and brain functions].

Obstructive sleep apnea syndrome (OSAS), a prevalent sleep disorder in children, is characterized by recurring upper airway obstruction during sleep. OSAS in children can cause intermittent hypoxia and sleep fragmentation, ultimately affect brain development and further lead to cognitive impairment if lack of timely effective intervention. In recent years, magnetic resonance imaging (MRI) and electroencephalogram (EEG) have been employed to investigate brain structure and function abnormalities in children with OSAS. Previous studies have indicated that children with OSAS showed extensive gray and white matter damage, abnormal brain function in regions such as the frontal lobe and hippocampus, as well as a significant decline in general cognitive function and executive function. However, the existing studies mainly focused on the regional activity, and the mechanism of pediatric OSAS affecting brain networks remains unknown. Moreover, it's unclear whether the alterations in brain structure and function are associated with their cognitive impairment. In this review article, we proposed two future research directions: 1) future studies should utilize the multimodal neuroimaging techniques to reveal the alterations of brain networks organization underlying pediatric OSAS; 2) further investigation is necessary to explore the relationship between brain network alteration and cognitive dysfunction in children with OSAS. With these efforts, it will be promising to identify the neuroimaging biomarkers for monitoring the brain development of children with OSAS as well as aiding its clinical diagnosis, and ultimately develop more effective strategies for intervention, diagnosis, and treatment.

Dysregulated lncRNAs are involved in the progress of myocardial infarction by constructing regulatory networks.

Long noncoding RNAs (lncRNAs) mediate important epigenetic regulation in a wide range of biological processes. However, the effect of all dysregulated lncRNAs in myocardial infarction (MI) is not clear. Whole transcriptome sequencing analysis was used to characterize the dynamic changes in lncRNA and mRNA expression. A gene network was constructed, and genes were classified into different modules using WGCNA. In addition, for all dysregulated lncRNAs, gene ontology analysis and cis-regulatory analysis were applied. The results demonstrated that a large number of the differentially co-expressed genes were primarily linked to the immune system process, inflammatory response, and innate immune response. The functional pathway analysis of the MEblue module included immune system process and apoptosis, and MEbrown included the T-cell receptor signal pathway by WGCNA. In addition, through cis-acting analysis of lncRNA regulation, the cis-regulated mRNAs were mainly enriched in immune system processes, innate immune responses, and VEGF signal pathways. We found that lncRNA regulation of mRNAs plays an important role in immune and inflammatory pathways. Our study provides a foundation to further understand the role and potential mechanism of dysregulated lncRNAs in the regulation of MI, in which many of them could be potential targets for MI.

Identification of key programmed cell death-related genes and immune infiltration in extracorporeal membrane oxygenation treatment for acute myocardial infarction based on bioinformatics analysis.

Background: Extracorporeal membrane oxygenation (ECMO) is an important clinical treatment for acute myocardial infarction (AMI) combined with cardiogenic shock, but the role of programmed cell death (PCD)-related genes in prognostication has not yet been investigated. Therefore, we explored the key prognostic biomarkers and immune infiltration in ECMO treatment in AMI combined with cardiogenic shock. Methods: The GSE93101 dataset was analyzed from the Gene Expression Omnibus (GEO) database, and the expression levels of PCD-related genes in AMI under ECMO were identified. Differentially expressed PCD-related genes between successful and failed treatment samples were analyzed, and Least absolute shrinkage and selection operator (LASSO) logistic regression and random forest were used to screen PCD-related molecular markers for ECMO treatment in AMI combined with cardiogenic shock. Co-expressed regulatory network and enrichment functions of the hub PCD-related genes were performed. In addition, the single-sample gene set enrichment analysis (ssGSEA) algorithm was used to calculate the immune cell infiltration of the ECMO treatment samples. Results: A total of 115 differentially expressed genes were identified from the GSE93101 dataset, and 76 genes were associated with PCD. Then, two hub PCD-related genes, Cell division cycle associated 7 (CDCA7), ankyrin repeat and SOCS box containing 13 (ASB13) were identified as prognostic markers of ECMO treatment in AMI combined with cardiogenic shock. The most significant Gene Ontology (GO) enriched terms of the co-expressed protein of ASB13 are related to post-translational protein modification, cullin-RING ubiquitin ligase complex, and cullin family protein binding, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that ubiquitin mediated proteolysis is the most enriched pathway. The results of GO and KEGG analysis in CDCA7 were mainly involved in DNA and cell cycle related activities and pathways. Moreover, we found that the successful treatment samples contained a lower proportion of nature killer T cells using immune infiltration analysis. Immune cell infiltration analysis revealed that ASB13 was positively correlated with natural killer cell (r = 0.591, p = 0.026), monocyte (r = 0.586, p = 0.028), and gamma delta T cell (r = 0.562, p = 0.036). Conclusion: The results of this study showed that ASB13 and CDCA7 may contribute to the occurrence and progression of AMI with cardiogenic shock under ECMO.

Au-Se bonded nanoprobe for prostate specific antigen detection in serum.

The detection of prostate specific antigen (PSA) in serum can realize early diagnosis of prostate cancer and prevent the occurrence of prostate tumors, as well as offering guidance during the therapy. Herein, a Au-Se bonded nanoprobes that can specifically detect PSA was designed and constructed. The peptide chains that can be specifically cleaved by PSA were firstly functionalized with fluorescent dye and selenol, and then bind to the Au nanoparticles to produce the probe. The dye's fluorescence was quenched due to the FRET effect, but recovered by PSA's cutting. The nanoprobe can detect PSA in serum with extraordinary anti-interference ability against other proteins (detection range 1-40 ng/mL). This work provides a new method for the detection of PSA in serum, and has potential guiding significance for clinical PSA detection.

Walnut-Derived Peptide Enhances Mitophagy via JNK-Mediated PINK1 Activation to Reduce Oxidative Stress in HT-22 Cells.

Mitophagy has a neuroprotective effect on reactive oxygen species (ROS)-induced neurodegenerative diseases. The walnut-derived polypeptide (TW-7) has antioxidant activity and protects nerves by promoting autophagy. However, its action mechanism against oxidative stress through mitophagy remains obscure. Therefore, we aimed to assess the effects of TW-7 on HT-22 cells under oxidative stress. Mitochondrial ultrastructure and cristae number were observed by transmission electron microscopy. The results showed that TW-7 (100 µM) restored the fluorescence intensity of the mitochondrial membrane potential to 0.99 ± 0.04 (P < 0.05), decreased H2O2-induced opening of mitochondrial permeability transition pores, and inhibited mitochondrial bioenergetic deficits. Moreover, it significantly increased activities of antioxidant enzymes to 186.88 ± 5.40 U/mgprot, 40.08 ± 0.87 mU/mgprot, and 23.57 ± 0.77 U/mgprot (P < 0.05), based on superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) assay results, respectively. Consistently, it decreased cellular and mitochondrial ROS levels by 51.71 ± 0.81 and 49.75 ± 0.69% (P < 0.05). TW-7 also downregulated C-Jun N-terminal kinase (JNK) phosphorylation and activated PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy in H2O2-induced HT-22 cells treated with JNK activator (anisomycin) and inhibitor (SP600125). Furthermore, TW-7 inhibited the mitochondrial apoptosis pathway by downregulation of the cytoplasmic cytochrome C, caspase-9, and cleaved-caspase-3 expression. Additionally, BDNF and SNAP-25 levels significantly increased to protect the synaptic function. Collectively, TW-7 improved oxidative stress-mediated nerve cell injury via JNK-regulated PINK1-mediated mitophagy.

Presence of the apolipoprotein E-ε4 allele is associated with an increased risk of sepsis progression.

Growing evidence indicated that single nucleotide polymorphisms (SNPs) in the apolipoprotein E (APOE) gene are related to increase the risk of many inflammatory-related diseases. However, few genetic studies have associated the APOE gene polymorphism with sepsis. This study was to investigate the clinical relevance of the APOE gene polymorphism in the onset and progression of sepsis. A multicenter case-control association study with a large sample size (601 septic patients and 699 healthy individuals) was conducted. Clinical data showed that the APOEε4 allele was overrepresented among all patients with septic shock (p = 0.031) compared with sepsis subtype, suggesting that APOEε4 allele may associated with increased susceptibility to the progression of sepsis. Moreover, the APOE mRNA levels decreased after lipopolysaccharide (LPS) stimulation in cells in culture. Then 21 healthy individuals to extract PBMC for genotype grouping (APOE4+ group 8; APOE4- group 13) was selected to evaluate the effect on APOE level, and results showed that the expression level of APOE in APOE4+ group and APOE4- group did not differ in mRNA levels after an LPS challenge, but the protein levels in APOE4+ group decreased slower than that in APOE4- group, and this process was accompanied by the upregulation of proinflammatory cytokines. These results provide evidence that the APOEε4 allele might be associated with the development of sepsis and a potential risk factor that can be used in the prognosis of sepsis.

RTN4B-mediated suppression of Sirtuin 2 activity ameliorates ß-amyloid pathology and cognitive impairment in Alzheimer's disease mouse model.

Sirtuin 2 (SIRT2) is an NAD+ dependent deacetylase that is the most abundant sirtuin protein in the brain. Accumulating evidence revealed the role of SIRT2 in a wide range of biological processes and age-related diseases. However, the pivotal mechanism of SIRT2 played in Alzheimer's disease (AD) remains unknown. Here, we report that pharmacological inactivation of SIRT2 has a beneficial effect in AD. The deacetylase inhibitor of SIRT2 rescued the cognitive impairment in amyloid precursor protein/presenilin 1 transgenic mouse (APP/PS1 mouse), and the BACE1 cleavage was weakened to reduce the ß-amyloid (Aß) production in the hippocampus. Moreover, we firstly identified that Reticulon 4B (RTN4B) played a crucial role between SIRT2/BACE1 regulation in AD. RTN4B, as a deacetylation substrate for SIRT2, the deacetylation by SIRT2 drived the ubiquitination and degradation of RTN4B and then the disturbed RTN4B interacted with and influenced the expression of BACE1. When we overexpressed RTN4B in neurons of the hippocampus in the AD mouse model, the abnormal Aß accumulation and cognitive impairment were ameliorated, consistent with the results of SIRT2 inhibition in vivo. Moreover, we showed that the regulatory effect of SIRT2 on BACE1 is dependent on RTN4B. When RTN4B was knocked down, the effects of SIRT2 inhibition on the BACE1 level, Aß pathology, and AD-liked behaviors were also blocked. Collectively, we provide evidence that SIRT2 may be a potential target for AD; the new found SIRT2/RTN4B/BACE1 pathological pathway is one of the critical mechanisms for the improvement of SIRT2 on AD.

Self-assembly of polyelectrolyte diblock copolymers within mixtures of monovalent and multivalent counterions.

In this study, the self-assembly behavior of polyelectrolyte (PE) diblock copolymers in solutions containing mixtures of monovalent and multivalent counterions was investigated using molecular dynamics simulation. The properties of the assembled micelles and counterion condensations at different charge fractions of multivalent ions have been discussed. The bridging effect of multivalent ions induces the electrostatic correlations of the PE chains, leading to the fusion of large micelles and the formation of bulky aggregates. Notably, lamellar and well-organized face-centered cubic (FCC) arrangements of the assembled micelles were observed in the mixture of monovalent and trivalent ions. At large fractions of multivalent ions, cylindrical and lamellar precipitates composed of the assembled micelles were formed owing to the inter-connecting coronas. The mixtures of monovalent and multivalent counterions allow the regulation of the electrostatic interactions and tuning of the properties in assembled micelles.