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Abstract The interaction between diet and the immune system has garnered considerable attention, especially regarding the immunomodulatory effects of food‐derived peptides. These peptides, derived from dietary proteins, exhibit diverse mechanisms of action, influencing cytokine production, immune cell function, and gut barrier integrity. Although there are numerous in vitro and animal studies supporting its therapeutic potential in immune‐related diseases, clinical relevance requires further investigation. This review synthesizes current knowledge on food‐derived peptides as immunomodulators, highlighting clinical insights and discussing challenges in their application. Additionally, it expands beyond peptides to encompass various dietary compounds influencing immune function. By integrating structural and functional diversity, this review provides a comprehensive understanding of how nutrition shapes immune responses, offering insights for personalized health strategies.

Abstract Objectives This study investigates curcumin's neuroprotective role and its potential in promoting neurogenesis in progenitor cells within the brain. Notably, curcumin's antioxidant properties have been implicated in Alzheimer's disease treatment. However, the association between curcumin's antioxidative effects and its impact on neural stem cells (NSCs) remains to be elucidated. Methods C17.2 neural stem cells were utilized as a model to simulate oxidative stress, induced by hydrogen peroxide (H2O2). We quantified the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and intracellular reactive oxygen species (ROS), alongside the gene expression of SOD1 and SOD2, to assess intracellular oxidative stress. Additionally, Western blot analysis was conducted to measure the expressions of LC3‐II, Beclin‐1, and phosphorylated ERK (p‐ERK), thereby evaluating autophagy and ERK signaling pathway activation. Results Treatment with curcumin resulted in a reduction of MDA and ROS levels, suggesting a protective effect on NSCs against oxidative damage induced by H2O2. Furthermore, a decrease in the relative expressions of LC3‐II, Beclin‐1, and p‐ERK was observed post‐curcumin treatment. Conclusions The findings suggest that curcumin may confer protection against oxidative stress by attenuating autophagy and deactivating the ERK1/2 signaling pathways, which could contribute to therapeutic strategies for Alzheimer's disease.

Abstract Estrogen receptor α (ERα) plays a crucial role in regulating glucose and energy homeostasis during type 2 diabetes mellitus (T2DM). However, the underlying mechanisms remain incompletely understood. Here we find a ligand-independent effect of ERα on the regulation of glucose homeostasis. Deficiency of ERα in the liver impairs glucose homeostasis in male, female, and ovariectomized (OVX) female mice. Mechanistic studies reveal that ERα promotes hepatic insulin sensitivity by suppressing ubiquitination-induced IRS1 degradation. The ERα 1-280 domain mediates the ligand-independent effect of ERα on insulin sensitivity. Furthermore, we identify a peptide based on ERα 1-280 domain and find that ERα-derived peptide increases IRS1 stability and enhances insulin sensitivity. Importantly, administration of ERα-derived peptide into obese mice significantly improves glucose homeostasis and serum lipid profiles. These findings pave the way for the therapeutic intervention of T2DM by targeting the ligand-independent effect of ERα and indicate that ERα-derived peptide is a potential insulin sensitizer for the treatment of T2DM.

BackgroundHypoxia has been found to cause cellular dysfunction and cell death, which are essential mechanisms in the development of acute myocardial infarction (AMI). However, the impact of hypoxia-related genes (HRGs) on AMI remains uncertain.MethodsThe training dataset GSE66360, validation dataset GSE48060, and scRNA dataset GSE163956 were downloaded from the GEO database. We identified hub HRGs in AMI using machine learning methods. A prediction model for AMI occurrence was constructed and validated based on the identified hub HRGs. Correlations between hub HRGs and immune cells were explored using ssGSEA analysis. Unsupervised consensus clustering analysis was used to identify robust molecular clusters associated with hypoxia. Single-cell analysis was used to determine the distribution of hub HRGs in cell populations. RT-qPCR verified the expression levels of hub HRGs in the human cardiomyocyte model of AMI by oxygen-glucose deprivation (OGD) treatment in AC16 cells.ResultsFourteen candidate HRGs were identified by differential analysis, and the RF model and the nomogram based on 8 hub HRGs (IRS2, ZFP36, NFIL3, TNFAIP3, SLC2A3, IER3, MAFF, and PLAUR) were constructed, and the ROC curves verified its good prediction effect in training and validation datasets (AUC = 0.9339 and 0.8141, respectively). In addition, the interaction between hub HRGs and smooth muscle cells, immune cells was elucidated by scRNA analysis. Subsequently, the HRG pattern was constructed by consensus clustering, and the HRG gene pattern verified the accuracy of its grouping. Patients with AMI could be categorized into three HRG subclusters, and cluster A was significantly associated with immune infiltration. The RT-qPCR results showed that the hub HRGs in the OGD group were significantly overexpressed.ConclusionA predictive model of AMI based on HRGs was developed and strongly associated with immune cell infiltration. Characterizing patients for hypoxia could help identify populations with specific molecular profiles and provide precise treatment.

Abstract The expansion of low‐carbon power generation has led to increased complexity in the dispatching mode of the power system. To achieve low‐carbon economic operation for multi‐regional power systems, this study proposes a decentralized dispatch architecture and a bi‐level low‐carbon economic dispatching (LCED) model. At the upper level, the model proposes a carbon emission constraint mechanism that is tailored to the coordinated operation of multiple regions, aiming to minimize the total operating cost. At the lower level, the model considers the reduction of carbon emission obligation on the load side and introduces the carbon emission flow (CEF) theory to calculate the degree of reduction in carbon emission intensity. To accommodate the decentralized autonomy and information privacy of different regions, a distributed alternating direction method of multipliers (D‐ADMM) algorithm is adopted to solve the upper‐level problem for the multi‐regional power system, enabling the fully distributed solution of the bi‐level optimization problem. Finally, the effectiveness of the proposed bi‐level model is validated through a case study on the modified IEEE 39‐bus system, which demonstrates that the model can significantly reduce carbon emissions and improve the level of renewable power consumption.

Disturbances in the microbiota-gut-brain axis may contribute to the development of Alzheimer’s disease. Magnesium-L-threonate has recently been found to have protective effects on learning and memory in aged and Alzheimer’s disease model mice. However, the effects of magnesium-L-threonate on the gut microbiota in Alzheimer’s disease remain unknown. Previously, we reported that magnesium-L-threonate treatment improved cognition and reduced oxidative stress and inflammation in a double-transgenic line of Alzheimer’s disease model mice expressing the amyloid-β precursor protein and mutant human presenilin 1 (APP/PS1). Here, we performed 16S rRNA amplicon sequencing and liquid chromatography-mass spectrometry to analyze changes in the microbiome and serum metabolome following magnesium-L-threonate exposure in a similar mouse model. Magnesium-L-threonate modulated the abundance of three genera in the gut microbiota, decreasing Allobaculum and increasing Bifidobacterium and Turicibacter. We also found that differential metabolites in the magnesium-L-threonate-regulated serum were enriched in various pathways associated with neurodegenerative diseases. The western blotting detection on intestinal tight junction proteins (zona occludens 1, occludin, and claudin-5) showed that magnesium-L-threonate repaired the intestinal barrier dysfunction of APP/PS1 mice. These findings suggest that magnesium-L-threonate may reduce the clinical manifestations of Alzheimer’s disease through the microbiota-gut-brain axis in model mice, providing an experimental basis for the clinical treatment of Alzheimer’s disease.

Abstract Background Stress hyperglycemia ratio (SHR), associated with adverse outcomes in patients with ST-segment elevation myocardial infarction (STEMI), has several definitions. This study aims to assess the prognostic value of SHR, derived from hemoglobin A1c (HbA1c) or glycated albumin (GA), to mortality. Methods The study comprised 1,643 STEMI patients who underwent percutaneous coronary intervention (PCI) in two centers. SHR1 was calculated using fasting blood glucose (FBG)/GA, while SHR2 was calculated using the formula FBG/(1.59*HbA1c-2.59). The primary endpoints were in-hospital death and all-cause mortality, with a median follow-up duration of 1.56 years. Results Higher SHR1 and SHR2 values are associated with increased risks of in-hospital death and all-cause mortality. Each standard deviation increase in SHR1 corresponded to a 39% and 22% escalation in in-hospital death and all-cause mortality, respectively. The respective increases for SHR2 were 51% and 26%. Further examinations validated these relationships as linear. Additionally, the areas under the curve (AUC) for in-hospital death were not significantly different between SHR1 and SHR2 (p > 0.05). Incorporating SHR1 or SHR2 into the base model significantly improved the discrimination and risk reclassification for in-hospital and all-cause mortality. A subgroup analysis revealed that the effects of SHR1 and SHR2 were more pronounced in patients with hypercholesteremia. Conclusion SHR1 and SHR2 have emerged as robust and independent prognostic markers for STEMI patients undergoing PCI. The SHR calculation based on either HbA1c or GA can provide additional predictive value for mortality beyond traditional risk factors, helping to identify high-risk STEMI patients.

Introduction: Dementia is marked by a steady decline or worsening in cognitive abilities, affecting memory, logic, and social competencies. While many studies suggest a potential link between the amount of sleep and dementia risk, the outcomes are not yet consistent. This research delved into the relationship between sleep length and bedtime on cognitive abilities using an extensive dataset from the China Family Panel Studies (CFPS) from 2014 to 2020. Methods: Data from 175,702 observations were collected, including cognitive function test data from 22,848 participants. Various cognitive tests were used to assess cognitive function. Restricted cubic spline (RCS) models were used for data analysis. Results: The optimal sleep duration for cognitive function was found to be 6–7 h, and the optimal bedtime was generally between 22:00–23:00. Longitudinal analysis revealed that sleep duration four years prior had a significant impact on current cognitive function. After accounting for various factors, those who slept for 7–8 h and over 8 h displayed lower cognitive function scores. Conversely, individuals sleeping less than 6 h had higher scores on the Vocabulary Test. Bedtime before 22:00 was associated with lower scores on the Vocabulary Test and Mathematical Test. Subgroup analyses based on age, gender, and urban residence showed variations in optimal sleep duration for different populations. Propensity Score Matching (PSM) analysis supported the findings. Conclusions: Maintaining a sleep duration of 6–7 h and a regular bedtime between 22:00–23:00 is important for optimizing cognitive performance.

Background: Allergen immunotherapy (AIT) is still the only treatment that may affect the natural cause of allergic disease. This study is to investigate whether an accelerated up-dosing scheme for subcutaneous allergen immunotherapy (SCIT) using a native house dust mite (HDM) allergen extract is as safe as the standard 3-strengths dose-escalation scheme in children with moderate to severe allergic rhinitis or rhinoconjunctivitis with or without asthma in China. Methods: In this multicenter, open label, randomized controlled trial, the children aged 5–14 years were randomized 1:1 either to One Strength group or the Standard group. The dose escalation scheme for patients in the One Strength group included 6 injections of strength 3, whereas the Standard group comprised 14 injections using strength 1, 2, and 3. All treatment-emergent adverse events (TEAEs) were recorded and analyzed. The 5-point Likert scale was used to assess tolerability (ChiCTR2100050311). Results: Overall, 101 children were included in the Safety Set (One Strength group: 50 vs. Standard group: 51). A total of 26 TEAEs were reported for 15 children. TEAEs related to AIT occurred in 10 % of the children in the One Strength group and 11.8 % of the Standard group. The number of systemic adverse reactions was comparable in both groups (One Strength: 5 vs. Standard: 4). No serious TEAEs was recorded for either group. 90.0 % of patients in the One Strength group reached the maintenance dose without an interventional dose adjustment due to adverse events, compared to 78.4 % in the Standard group. All patients who completed the dose-escalation phase reached the recommended maintenance dose of 1.0 ml of strength 3.Investigators and patients rated the tolerability of the One Strength regimen slightly better than the Standard scheme. Conclusions: This exploratory study suggests that the accelerated One Strength dose-escalation scheme is comparable in safety and tolerability to the Standard regimen. However, due to the preliminary nature and small sample size, further research with larger sample sizes and robust study designs is necessary for confirmation.

As "the island at the center of the world," Manhattan has inspired countless writers and has served as a spatial archetype in science fiction's world-building. From the interdisciplinary perspective of literature and economics, this article discusses the crisis imagination of the "bubble metropolis" in five contemporary Manhattan-related science fiction novels including *Cities in Flight* (1970), *The Blister* (1975), *Terminal World* (2010), *Zone One* (2011), and *New York 2140* (2017). The spatial variety of Manhattan Island in these science fiction novels is closely combined with its economic condition. The characters, plots, and spatial imagery of these novels gather to reflect the different stages of the operation of a bubble economy, illustrating a historical cycle of capitalism that can never be escaped. Manhattan Island has long been the symbol of the world's rush for wealth. The fear of economic recession, environmental degradation, and class conflict have formed the special geographical features of the island in the future. The crisis imagination of the "bubble metropolis" also seeks to stimulate critical thinking on economic ethics, urban design, and high technology, calling for social justice and public welfare.

Bénard–Marangoni convection in an open cavity has attracted much attention in the past century. In most of the previous works, liquids with Prandtl numbers larger than unity were used to study in this issue. However, the Bénard–Marangoni convection with liquids at Prandtl numbers lower than unity is still unclear. In this study, Bénard–Marangoni convection in an open cavity with liquids at Prandtl numbers lower than unity in zero-gravity conditions is investigated to reveal the bifurcations of the flow and quantify the heat and mass transfer. Three-dimensional direct numerical simulation is conducted by the finite-volume method with a SIMPLE scheme for the pressure–velocity coupling. The bottom boundary is nonslip and isothermal heated. The top boundary is assumed to be flat, cooled by air and opposed by the Marangoni stress. Numerical simulation is conducted for a wide range of Marangoni numbers (Ma) from 5.0 × 101 to 4.0 × 104 and different Prandtl numbers (Pr) of 0.011, 0.029, and 0.063. Generally, for small Ma, the liquid metal in the cavity is dominated by conduction, and there is no convection. The critical Marangoni number for liquids with Prandtl numbers lower than unity equals those with Prandtl numbers larger than unity, but the cells are different. As Ma increases further, the cells pattern becomes irregular and the structure of the top surface of the cells becomes finer. The thermal boundary layer becomes thinner, and the column of velocity magnitudes in the middle slice of the fluid is denser, indicating a stronger convection with higher Marangoni numbers. A new scaling is found for the area-weighted mean velocity magnitude at the top boundary of um~Ma Pr−2/3, which means the mass transfer may be enhanced by high Marangoni numbers and low Prandtl numbers. The Nusselt number is approximately constant for Ma ≤ 400 but increases slowly for Ma > 400, indicating that the heat transfer may be enhanced by increasing the Marangoni number.

BackgroundThis study examined national similarities and differences in people's engagement in health preventive behaviors during a public health crisis, as well as investigated the underlying individual-level psychological mechanisms. A conceptual distinction was made between self-focused and other-involved preventive behaviors in response to public health crises.MethodTwo cross-sectional surveys were conducted in the United States (N = 888) and China (N = 844) during the early stage of the COVID-19 pandemic. Hayes' PROCESS was utilized to assess national differences in seven preventive behaviors, along with the mediating effects of self-construal and health locus of control.ResultsThe results showed that American participants reported greater engagement in self-focused preventive behaviors than Chinese, whereas Chinese participants reported greater engagement in other-involved preventive behaviors than Americans. Chinese participants also engaged more in other-involved than self-focused preventive behaviors. Self-construal and health locus of control partially explained the observed differences in engagement in preventive behaviors.DiscussionThis study introduces a culture-sensitive approach to provide insights for crafting communication interventions that can enhance the effectiveness of health campaigns in the context of a public health crisis.

in the context of the rapid development of wireless communication networks, it explores the relationship between environmental, social, and governance (ESG) scores and corporate financing technical efficiency (TE).

In the 21st century, cardiovascular disease (CVD) has become one of the leading causes of death worldwide. The prevention and treatment of CVD remain pressing scientific issues. Several recent studies have suggested that ferroptosis may play a key role in CVD. Most studies conducted thus far on ferroptosis and CVD have supported the link. Ferroptosis mediated by different signaling and metabolic pathways can lead to ischemic heart disease, myocarditis, heart failure, ischemia-reperfusion injury, and cardiomyopathy. Still, the specific mechanism of ferroptosis in CVD, the particular organ areas affected, and the stage of disease involved need to be further studied. Therefore, understanding the mechanisms regulating ferroptosis in CVD may improve disease management. Throughout this review, we summarized the mechanism of ferroptosis and its effect on the pathogenesis of CVD. We also predicted and discussed future research directions, aiming to provide new ideas and strategies for preventing and treating CVD.

IntroductionFood proteins have been recognized as an ideal source to release bioactive peptides with the potential to intervene nutrition related chronic diseases, such as cardiovascular diseases, obesity and diabetes. Our previous studies showed that pea protein hydrolysate (PPH) could suppress hepatic glucose production in hepatic cells via inhibiting the gluconeogenic signaling. Thus, we hypothesized that PPH could play the hypoglycemic role in vivo.MethodsIn the present study, the mice model with type 2 diabetic mellitus (T2DM) was developed by high-fat diet and low dose of streptozotocin injections. PPH was administered orally with a dosage of 1000 mg/kg body weight for 9 weeks, followed by the downstream biomedical analyses.ResultsThe results showed that the 9-week treatment of PPH could reduce fasting blood glucose by 29.6% and improve glucose tolerance in the T2DM mice. The associated mechanisms included suppression of the gluconeogenic pathway, activation of the insulin signaling and modulation of the renin angiotensin system in the liver of the diabetic mice. In addition, the levels of pro-inflammatory markers in both liver and serum were reduced by the PPH treatment.ConclusionThe hypoglycemic effect of PPH in T2DM mice was demonstrated in the present study. Findings from this study could provide rationale to incorporate PPH into functional foods or nutraceuticals for glycemic control.

Abstract Objective We explored the dietary effects of replacing normal dietary staple foods with supplementary nutritional protein powder, dietary fiber, and fish oil on several metabolic parameters. We examined weight loss, glucose and lipid metabolism, and intestinal flora in obese individuals when compared with individuals on a reduced staple food low carbohydrate diet. Methods From inclusion and exclusion criteria, 99 participants (28 kg/m2 ≤ body mass index (BMI) ≤ 35 kg/m2) were recruited and randomly assigned to control and intervention 1 and 2 groups. Physical examinations and biochemical indices were performed/gathered before the intervention and at 4 and 13 weeks post intervention. After 13 weeks, feces was collected and 16s rDNA sequenced. Results After 13 weeks, when compared with controls, body weight, BMI, waist circumference, hip circumference, systolic blood pressure, and diastolic blood pressure values in intervention group 1 were significantly reduced. In intervention group 2, body weight, BMI, waist circumference, and hip circumference were significantly reduced. Triglyceride (TG) levels in both intervention groups were significantly reduced. Fasting blood glucose, glycosylated hemoglobin, glycosylated albumin, total cholesterol, and apolipoprotein B levels in intervention group 1 were decreased, while high density lipoprotein cholesterol (HDL-c) decreased slightly. Glycosylated albumin, TG, and total cholesterol levels in intervention group 2 decreased, while HDL-c decreased slightly, High sensitive C-reactive protein, MPO, Ox-LDL, LEP, TGF-β1, IL-6, GPLD1, pro NT, GPC-4, and LPS levels in both intervention groups were lower when compared with controls. Adiponectin (ADPN) levels in intervention groups were higher when compared with controls. Tumor necrosis factor-α (TNF-α) levels in intervention group 1 were lower when compared with controls. There is no obvious difference in α diversity and β diversity between intestinal flora of 3 groups. Among the first 10 species of Phylum, only the control group and the intervention group 2 had significantly higher Patescibacteria than the intervention group 1. Among the first 10 species of Genus, only the number of Agathobacter in intervention group 2 was significantly higher than that in control group and intervention group 1. Conclusions We showed that an LCD, where nutritional protein powder replaced some staple foods and dietary fiber and fish oil were simultaneously supplemented, significantly reduced weight and improved carbohydrate and lipid metabolism in obese individuals when compared with an LCD which reduced staple food intake.

N6-methyladenosine (m6A) methylation of RNA is a common type of RNA modification that regulates gene expression. Here, the authors report m6A methylation of serpin 2 A negatively regulates inflammation and reduces heart dysfunction in the setting of sepsis.

Background: Overweight and obesity as main health problems harm human beings worldwide. The number of people diagnosed with overweight and obese is gradually increasing. Green tea catechin has been reported to effectively help control body weight in overweight and obese population, and is protectively against the blood pressure and lipids in people with type 2 diabetes and metabolic syndrome. Methods: We retrieved 4 English databases (PubMed, Web of science, Cochrane, Scoups) from inception to April 20, 2023. Two reviewers independently determined eligibility, assessed the reporting quality of included studies, and extracted the data. Data were extracted from eleven studies. The results were presented with the weighted mean differences (WMDs), and the confidence intervals (CIs) was 95 %. The random-effects or fixed-effects model was applied according to the heterogeneity. The subgroup analysis was used to identify the source of heterogeneity. Publication bias was evaluated using funnel plots, Egger's test, and Begg's test. Results: Eleven randomized controlled trials (RCTs) inclusion studies were screened from 3072 literature articles, involving 613 overweight and obese patients. After combining all studies, it was found that in overweight and obese people green tea catechin could reduce waist circumference (WC) (pooled WMD = −1.37 cm, 95 % CI: −2.52 to −0.22 cm, p = 0.019), and triglyceride (TG) (pooled WMD = −0.18 mmol/L, 95 % CI: −0.35 to −0.02 mmol/L, p = 0.032), and increase high density lipoprotein cholesterol (HDL-c) (pooled WMD = 0.07 mmol/L, 95 % CI: 0.01–0.14 mmol/L, p = 0.031). Conclusion: Green tea catechin supplement effectively reduced WC and TG levels and improved HDL-c levels. However, it did not show the significant effect on the blood pressure in overweight and obese people. The present meta-analysis showed a moderate benefit of green tea catechin supplementation on lipid profiles in overweight and obese people.

BackgroundThe effect of viscous soluble dietary fiber on glucose and lipid metabolism in type 2 diabetes mellitus (T2DM) remains controversial, and the dose–response relationship of its effect on blood glucose and blood lipid level is still unclear.MethodsWe conducted comprehensive searches in several databases up to 17 January 2023. We conducted a dose–response analysis of randomized controlled trials (RCTs) to investigate the effect of viscous dietary fiber on glucose and lipid metabolism in patients with T2DM.ResultsStatistical significance was observed in the decreases of glycosylated hemoglobin (HbA1c) (mean difference) [MD = −0.47; 95%CI: (−0.66, −0.27)], fasting blood glucose (FBG) [MD = −0.93; 95%CI: (−1.46, −0.41)], total cholesterol (TC) [MD = −0.33; 95%CI: (−0.46, −0.21)], and low-density lipoprotein and cholesterol (LDL-C) [MD = −0.24; 95%CI: (−0.35, −0.13)]. Contrarily, no difference was observed regarding the level of high-density lipoprotein cholesterol (HDL-C) or triglyceride (TG). In addition, the effect on fasting insulin remains unclear. Results from the subgroup analyses showed that an intervention duration longer than 6 weeks had a significant effect on the HbA1c level; a treatment dosage higher than 8.3 g/day had a significant effect on the FBG level.ConclusionsSupplementation of viscous dietary fiber is beneficial to control blood glucose and blood lipid in T2DM.

With global climate change, increasingly frequent natural disasters have brought great challenges to the safe and reliable power supply and low-carbon transition of power distribution systems. Most of the existing researches on the distribution system under the impact of natural disasters only focus on the improvement of power supply reliability, but have not consider the impact of disaster severity and disaster response measures on carbon emissions. In order to juggle the load restoration and carbon emission mitigation of distribution system under natural disasters, this paper proposes an optimal allocation method of distributed renewable generations (DRGs) considering carbon emission for multi-scenario natural disasters based on the framework of cyber-physical-social system in energy (CPSSE), and establishes a three-stage optimization model of pre-disaster prevention-disaster attack-post-disaster restoration. For the purpose of ensuring the practicability and robustness of the allocation results, the disaster scenario is modeled and the selection method of the worst fault scenario under disaster is proposed. The progressive hedging algorithm (PHA) is adopted to solve the proposed multi-scenario optimization problem. Finally, the simulation results indicate that the proposed method can restore more lost load at a lower cost of carbon emissions.

Abstract Background Alzheimer's disease (AD) is the most common neurodegenerative disorder without effective therapy and lack diagnosis strategy for preclinical AD patients. There is an urgent need for development of both early diagnosis and therapeutic intervention of AD. Results Herein, we developed a nanotheranostics platform consisting of Curcumin (Cur), an anti-inflammatory molecule, and superparamagnetic iron oxide (SPIO) nanoparticles encapsulated by diblock 1,2-dio-leoyl-sn-glycero-3-phosphoethanolamine-n-[poly(ethylene glycol)] (DSPE-PEG) that are modified with CRT and QSH peptides on its surface. Furthermore, we demonstrated that this multifunctional nanomaterial efficiently reduced β-amyloid plaque burden specifically in APP/PS1 transgenic mice, with the process noninvasively detected by magnetic resonance imaging (MRI) and the two-dimensional MRI images were computed into three-dimension (3D) plot. Our data demonstrated highly sensitive in vivo detection of β-amyloid plaques which more closely revealed real deposition of Aβ than previously reported and we quantified the volumes of plaques for the first time based on 3D plot. In addition, memory deficits of the mice were significantly rescued, probably related to inhibition of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasomes. Conclusions Gathered data demonstrated that this theranostic platform may have both early diagnostic and therapeutic potential in AD. Graphical Abstract

Abstract The nuclear N6‐methyladenosine (m6A) reader YT521‐B homology‐domain‐containing protein 1 (YTHDC1) is required to maintain embryonic stem cell identity. However, little is known about its biological functions in intestinal‐resident macrophages and inflammatory bowel disease (IBD). Herein, it is demonstrated that macrophage‐specific depletion or insufficiency of YTHDC1 accelerates IBD development in animal models. On the molecular basis, YTHDC1 reduction in IBD‐derived macrophages is attributed to Zinc finger protein 36 (ZFP36)‐induced mRNA degradation. Importantly, transcriptome profiling and mechanistic assays unveil that YTHDC1 in macrophages regulates Ras homolog family member H (RHOH) to suppress inflammatory responses and fine‐tunes NME nucleoside diphosphate kinase 1 (NME1) to enhance the integrity of colonic epithelial barrier, respectively. Collectively, this study identifies YTHDC1 as an important factor for the resolution of inflammatory responses and restoration of colonic epithelial barrier in the setting of IBD.

With demand for the long-term continued use of existing building facilities, structural health monitoring and damage detection are attracting interest from society. Sensors of various types have been practically applied in the industry to satisfy this need. Among the sensors, piezoelectric sensors are an extremely promising technology by virtue of their cost advantages and durability. Although they have been used in aerospace and civil engineering, their application for building engineering remains limited. Remarkably, recent catastrophic seismic events have further reinforced the necessity of rapid damage detection and quick judgment about the safe use of facilities. Faced with these circumstances, this study was conducted to assess the applicability of piezoelectric sensors to detect damage to building components stemming from concrete cracks and local buckling. Specifically, this study emphasizes structural damage caused by earthquakes. After first applying them to cyclic loading tests to composite beam component specimens and steel frame subassemblies with a folded roof plate, the prospective damage positions were also found using finite element analysis. Crack propagation and buckling locations were predicted adequately. The piezoelectric sensors provided output when the concrete slab showed tensile cracks or when the folded roof plate experienced local buckling. Furthermore, damage expansion and progression were detected multiple times during loading tests. Results showed that the piezoelectric sensors can detect the structural damage of building components, demonstrating their potential for use in inexpensive and stable monitoring systems.

Packaging plastics are called ‘single-use plastics’ because of short lifetime. Among which, the three plastics of polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET) take more than 70%. Due to incompatibility, few research has been done on the alloy of the three plastics. The aim of this study is to investigate the possibility of single-use plastic alloy (SUPA) of ternary PE, PP, and PET as the 3D printing material. Tensile and bending tests are carried out to investigate the mechanical properties, photographs of scanning electron microscope (SEM) are taken for morphology analysis, and differential scanning calorimetry (DSC) are used to study the crystallization behavior of the alloys. The results show that there is an optimal ratio for all the components to obtain the best mechanical performances, i.e., the ratio of PP/PE=40/60 with 20 wt% PET, 2 wt% maleic anhydride grafted polypropylene (PP-g-MAH) and 2 wt% organic modified montmorillonite (OMMT). This SUPA has a tensile strength of 14.48 MPa, a tensile modulus of 586.42 MPa, a flexural strength of 15.85 MPa, and a flexural modulus of 544.67 MPa. Due to the function of compatibilizer and nanoclay (NC) will be affected by redundancy, the potential primary fibrosis while collecting the feeding filaments and the secondary fibrosis at the nozzle of 3D printing might be responsible for the variation of the mechanical performances.

Background and objectiveAlzheimer’s disease (AD) is characterized by amyloid β (Aβ) aggregation and neuroinflammation. This study aimed to investigate the therapeutic effect of isoniazid (INH) against AD.MethodsThe APP/PS1 transgenic mouse model of AD was adopted. The APP/PS1 mice received oral INH (45 mg/kg/d) for 14 days. The cognitive capability was assessed by the Morris Water Maze test. Amyloid plaques and Aβ levels were determined by immunohistochemistry and ELISA assay. The dendritic spines were analyzed by DiOlistic labeling. Immunofluorescence staining was used to observe the microglia and astrocytes.ResultsThe Morris Water Maze test suggested that INH administration can effectively attenuate the reference memory deficit and improve the working memory of the APP/PS1 mice compared to the untreated mice (all p

Background and objectiveAlzheimer’s disease (AD) is the most common type of dementia, with its pathology like beta-amyloid and phosphorylated tau beginning several years before the clinical onset. The aim is to identify genetic risk factors associated with the onset of AD.MethodsWe collected three microarray data of post-mortem brains of AD patients and the healthy from the GEO database and screened differentially expressed genes between AD and healthy control. GO/KEGG analysis was applied to identify AD-related pathways. Then we distinguished differential expressed genes between symptomatic and asymptomatic AD. Feature importance with logistic regression analysis is adopted to identify the most critical genes with symptomatic AD.ResultsData was collected from three datasets, including 184 AD patients and 132 healthy controls. We found 66 genes to be differently expressed between AD and the control. The pathway enriched in the process of exocytosis, synapse, and metabolism and identified 19 candidate genes, four of which (VSNL1, RTN1, FGF12, and ENC1) are vital.ConclusionVSNL1, RTN1, FGF12, and ENC1 may be the essential genes that progress asymptomatic AD to symptomatic AD. Moreover, they may serve as genetic risk factors to identify high-risk individuals showing an earlier onset of AD.

Objective The present study aimed to investigate the application safety of bivalirudin combined with ticagrelor in the emergency percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). Methods From October 1, 2018, to December 30, 2019, 210 patients with STEMI admitted to the Department of Cardiology who underwent emergency PCI were randomly divided into the bivalirudin group (group A, N = 105) and the unfractionated heparin group (group B, N = 105). Before the emergency PCI operation after admission, the loading dose of aspirin (300 mg) was given orally, and then 100 mg/d. At the same time, the loading dose of ticagrelor (180 mg) was administered orally, and then 90 mg/bid. The adverse events and the hemorrhage events 30 days after the operation were observed and recorded. Results There were five hemorrhage cases in the bivalirudin group, with one case of secondary hemorrhage and four cases of mild hemorrhage. There were 14 hemorrhages in the unfractionated heparin group with one case of secondary hemorrhage and thirteen cases of mild hemorrhage. In terms of mild hemorrhage, the hemorrhage rate in the bivalirudin group was significantly lower than that in the unfractionated heparin group (3.8% vs. 12.4%, P = 0.040). One patient died in the unfractionated heparin group, while no deaths occurred in the bivalirudin group during the thirty days of follow-up. No myocardial infarction, revascularization, or stroke occurred in the two groups within 30 days after the operation. Conclusion Compared with unfractionated heparin combined with ticagrelor in patients with STEMI undergoing emergency PCI treatment, bivalirudin combined with ticagrelor could significantly reduce the occurrence of mild hemorrhage events, and it would not increase the incidence of MACE during the 30 days of follow-up.

Flaxseed oil (FO) has displayed potential anti-diabetes properties by providing a high content of α-linolenic acid. However, the effects and mechanisms of FO on type 1 diabetes are still unclear. The present study aims to explore the effects of different doses of FO feeding on hepatic inflammation and gut microbiota in streptozotocin-induced diabetic mice. Forty-eight six-week-old C57BL/6J male mice were divided into a control group (CON), a diabetic group (MOD), a diabetes with 7.0% w/w FO feeding group (FO-L), and a diabetes with 10.5% w/w FO feeding group (FO-H) for six weeks. The 7.0% w/w and 10.5% w/w FO feeding groups exhibited potential recovery of the number and size of pancreas tissues. The fasting blood glucose level was significantly decreased only after 4 weeks of feeding with 10.5% w/w FO in diabetic mice. The 10.5% w/w FO feeding group significantly decreased the postprandial blood glucose level of mice in the OGTT test. Hepatic glycogen levels were dramatically upregulated in the mice fed with both 7.0% w/w and 10.5% w/w FO. FO feeding significantly attenuated hepatic LPS, TNF-α, and IL-1β levels. In addition, we observed that 7.0% w/w and 10.5% w/w FO feedings notably downregulated hepatic gene and protein expressions of TLR4, MyD88, and P65. Furthermore, only 10.5% FO regulated fecal microbiota by increasing the relative abundance of the Bacteroidetes phylum, Lactococcus family, and Muribaculaceae and Streptococcaceae family and genus in streptozotocin-induced diabetic mice. Therefore, we conclude that FO feeding plays a role in anti-inflammation via the regulation of hepatic LPS/TLR4/MyD88 pathways and gut microbiota. In addition, different doses of FO supplementation may exhibit varying mechanisms in streptozotocin-induced mice.

Food protein-derived antihypertensive peptides are a representative type of bioactive peptides. Several models based on partial least squares regression have been constructed to delineate the relationship between the structure and activity of the peptides. Machine-learning-based models have been applied in broad areas, which also indicates their potential to be incorporated into the field of bioactive peptides. In this study, a long short-term memory (LSTM) algorithm-based deep learning model was constructed, which could predict the IC50 value of the peptide in inhibiting ACE activity. In addition to the test dataset, the model was also validated using randomly synthesized peptides. The LSTM-based model constructed in this study provides an efficient and simplified method for screening antihypertensive peptides from food proteins.

Abstract Background Vitamin D receptor (VDR) plays a vital protective role in oral and colonic epithelial cells. Albeit we know that VDR expression is reduced in the mucosal epithelial layers of autoimmune diseases, the mechanism by which VDR is decreased remains elusive. Methods VDR and zinc finger protein 36 (ZFP36) levels in human samples and cell lines were detected by real-time PCR, western blot and immunostaining. Luciferase report assay was used to test cis-elements in VDR gene promoter, real-time PCR was applied to measure mRNA decay and western blot was performed to evaluate protein degradation. RNA affinity chromatography assay was used to test protein-mRNA interaction. Co-immunoprecipitation was used to detect protein–protein interaction. The role of ZFP36 in AU-rich elements (AREs) in the 3′ untranslated region (UTR) of VDR mRNA was also measured by luciferase report assay. Results We identify ZFP36 can bind with the AREs in the 3’UTR of VDR mRNA, leading to mRNA degradation in oral and colonic epithelial cells under inflammatory circumstance. Either ZFP36 protein or AREs of VDR mRNA mutation abolishes this protein-mRNA binding process. After the key amino acid’s mutation, ZFP36 fails to decrease VDR mRNA expression. We also find that VDR physically binds with Y box-binding protein 1 (YBX-1) to block YBX-1’s nuclear translocation and ameliorate cell death in the presence of inflammation. Conclusion These findings provide insights into the cause of VDR decrease in oral and colonic epithelial cells under inflammatory condition and explain how VDR maintains cell viability in these cells. Video abstract

BackgroundWhite matter hyperintensities (WMHs) and regional brain lobe atrophy coexist in the brain of patients with Alzheimer's disease (AD), but the association between them in patients with AD still lacks comprehensive investigation and solid imaging data support.ObjectiveWe explored whether WMHs can promote the pathological process of AD by aggravating atrophy in specific brain regions and tried to explain the regional specificity of these relationships.MethodsA sample of 240 adults including 180 normal controls (NCs) and 80 cases with AD were drawn from the ADNI database. T1-weighted magnetic resonance imaging (MRI) and T2-weighted fluid-attenuated MRI of the participants were downloaded and were analyzed using AccuBrain® to generate the quantitative ratio of WMHs (WMHr, WMH volumes corrected by intracranial volume) and regional brain atrophy. We also divided WMHr into periventricular WMHr (PVWMHr) and deep WMHr (DWMHr) for the purpose of this study. The Cholinergic Pathways Hyperintensities Scale (CHIPS) scores were conducted by two evaluators. Independent t-test, Mann–Whitney U test, or χ2 test were used to compare the demographic characteristics, and Spearman correlation coefficient values were used to determine the association between WMHs and different regions of brain atrophy.ResultsPositive association between WMHr and quantitative medial temporal lobe atrophy (QMTA) (rs = 0.281, p = 0.011), temporal lobe atrophy (rs = 0.285, p = 0.011), and insular atrophy (rs = 0.406, p < 0.001) was found in the AD group before Bonferroni correction. PVWMHr contributed to these correlations. By separately analyzing the relationship between PVWMHr and brain atrophy, we found that there were still positive correlations after correction in QMTA (rs = 0.325, p = 0.003), temporal lobe atrophy (rs = 0.298, p = 0.007), and insular atrophy (rs = 0.429, p < 0.001) in AD group.ConclusionWMH severity tends to be associated with regional brain atrophy in patients with AD, especially with medial temporal lobe, temporal lobe, and insular lobe atrophy. PVWMHs were devoted to these correlations.

Abstract Background The differential diagnosis of frontotemporal dementia (FTD) and Alzheimer’s disease (AD) is difficult due to the overlaps of clinical symptoms. Structural magnetic resonance imaging (sMRI) presents distinct brain atrophy and potentially helps in their differentiation. In this study, we aim at deriving a novel integrated index by leveraging the volumetric measures in brain regions with significant difference between AD and FTD and developing an MRI-based strategy for the differentiation of FTD and AD. Methods In this study, the data were acquired from three different databases, including 47 subjects with FTD, 47 subjects with AD, and 47 normal controls in the NACC database; 50 subjects with AD in the ADNI database; and 50 subjects with FTD in the FTLDNI database. The MR images of all subjects were automatically segmented, and the brain atrophy, including the AD resemblance atrophy index (AD-RAI), was quantified using AccuBrain®. A novel MRI index, named the frontotemporal dementia index (FTDI), was derived as the ratio between the weighted sum of the volumetric indexes in “FTD dominant” structures over that obtained from “AD dominant” structures. The weights and the identification of “FTD/AD dominant” structures were acquired from the statistical analysis of NACC data. The differentiation performance of FTDI was validated using independent data from ADNI and FTLDNI databases. Results AD-RAI is a proven imaging biomarker to identify AD and FTD from NC with significantly higher values (p

ObjectiveThe aim of this systematic review and meta-analysis was to examine the association between high ratio of n-6/n-3 polyunsaturated fatty acids (PUFAs) and depression.MethodsThe authors conducted a meta-analysis of research articles on the association of high ratio of n-6/n-3 PUFAs with the risk of depression published in the online article database on PubMed, Embase, Cochrane library as of December 2021. Pooled odds ratios (OR) were calculated using random effects models. Publication bias was assessed visually by funnel plots and statistically by the Egger’s and Begg’s tests.ResultsFinally, 12 studies included in this systematic review and meta-analysis with a total of 66,317 participants (including 4,173 individuals with depression condition). The pooled results showed that high ratio of n-6/n-3 PUFAs might be positively associated with depression [OR = 1.21, 95% confidence intervals (CIs): 1.04∼1.41]. The I2 test indicated that there was a substantial statistical heterogeneity across the included studies (I2 = 54.38%, P = 0.01). Subgroup analysis showed that high ratio of n-6/n-3 PUFAs in blood had no significant association with depression (OR = 1.15, 95%CI: 0.88∼1.50), while high ratio of n-6/n-3 PUFAs in dietary supplements was positively associated with depression (OR = 1.32, 95%CI: 1.16∼1.51).ConclusionThis meta-analysis confirmed the association between high ratio of n-6/n-3 PUFAs and the risk of depression. High ratio of n-6/n-3 PUFAs in dietary supplementation was positively associated with depression, but had no significant association in the blood. This study suggested that lowering the dietary intake of the ratio of n-6/n-3 PUFAs would be beneficial in the prevention of depression.

Background and ObjectiveEarly identification is important for timely Alzheimer’s disease (AD) treatment. Apolipoprotein E ε4 allele (APOE-ε4) is an important genetic risk factor for sporadic AD. The AD-Resemblance Atrophy Index (RAI)—a structural magnetic resonance imaging-derived composite index—was found to predict the risk of progression from mild cognitive impairment (MCI) to AD. Therefore, we investigated whether the AD-RAI can predict cognitive decline and progression to AD in patients with MCI carrying APOE ε4.MethodsWe included 733 participants with MCI from the Alzheimer’s Disease Neuroimaging Initiative Database (ADNI). Their APOE genotypes, cognitive performance, and levels of AD-RAI were assessed at baseline and follow-up. Linear regression models were used to test the correlations between the AD-RAI and baseline cognitive measures, and linear mixed models with random intercepts and slopes were applied to investigate whether AD-RAI and APOE-ε4 can predict the level of cognitive decline. Cox proportional risk regression models were used to test the association of AD-RAI and APOE status with the progression from MCI to AD.ResultsThe baseline AD-RAI was higher in the MCI converted to AD group than in the MCI stable group (P < 0.001). The AD-RAI was significantly correlated with cognition, and had a synergistic effect with APOE-ε4 to predict the rate of cognitive decline. The AD-RAI predicted the risk and timing of MCI progression to AD. Based on the MCI population carrying APOE-ε4, the median time to progression from MCI to AD was 24 months if the AD-RAI > 0.5, while the median time to progression from MCI to AD was 96 months for patients with an AD-RAI ≤ 0.5.ConclusionThe AD-RAI can predict the risk of progression to AD in people with MCI carrying APOE ε4, is strongly correlated with cognition, and can predict cognitive decline.

Alzheimer’s disease (AD) is a prevalent neurodegenerative disease predominantly affecting millions of elderly people. To date, no effective therapy has been identified to reverse the progression of AD. Metformin, as a first-line medication for Type 2 Diabetes Mellitus (T2DM), exerts multiple beneficial effects on various neurodegenerative disorders, including AD. Evidence from clinical studies has demonstrated that metformin use contributes to a lower risk of developing AD and better cognitive performance, which might be modified by interactors such as diabetic status and APOE-ε4 status. Previous mechanistic studies have gradually unveiled the effects of metformin on AD pathology and pathophysiology, including neuronal loss, neural dysfunction, amyloid-β (Aβ) depositions, tau phosphorylation, chronic neuroinflammation, insulin resistance, impaired glucose metabolism and mitochondrial dysfunction. Current evidence remains ambiguous and even conflicting. Herein, we review the current state of knowledge concerning the mechanisms of metformin in AD pathology while summarizing current evidence from clinical studies.

Aims: The current study was conducted with the central objective of investigating the expression of microRNA-145 (miR-145) in renal vascular lesions (RVLs) in juvenile lupus nephritis (JLN) and its possible mechanism. Methods: The clinical data of 49 JLN patients confirmed by renal biopsy were collected and followed by grouping according to the RVLs score after hematoxylin-eosin staining: mild, moderate, and severe groups. In situ hybridization was used to detect the expression of miR-145 in renal vessels which was then being compared among different RVLs groups. Up-LV-miR-145 and LV-miR-NC lentiviral vectors were constructed and transfected into human vascular smooth muscle cells (HVSMCs), respectively. After HVSMCs were treated with 10.0 µg/L platelet-derived growth factor (PDGF)-BB for 24 h, the proliferation, migration, and apoptosis of endothelial cells were detected by MTT, Transwell assay, and flow cytometry, respectively. Western blot was used to detect expression of alpha-smooth muscle actin (α-SM-actin) and osteopontin (OPN). Results: The expression of miR-145 in renal vascular cells was statistically significant. The higher the inner membrane ratio, the lesser the miR-145 expression. After treatment with PDGF-BB, expression of miR-145 in HVSMCs decreased, proliferation and migration ability enhanced, apoptosis decreased, α-SM-actin decreased, and OPN increased. The proliferation and migration ability of HVSMCs in the LV-miR-145 group suppressed, apoptosis enhanced, α-SM-actin increased, and OPN decreased. Conclusions: Our study revealed that miR-145 expression decreased with the increase of vascular damage. miR-145 can inhibit proliferation, migration, and differentiation phenotypic transformation of HVSMCs induced by PDGF-BB. miR-145 may be involved in the pathogenesis of RVLs and may be a new target for treatment of RVLs in lupus nephritis.

Since the effects of mono-unsaturated fatty acids (MUFA) on lipid profile are still controversial, a meta-analysis of randomized controlled trials was conducted in the present study to assess the effect of MUFA-rich food on lipid profiles. The study was designed, conducted, and reported according to the guidelines of the 2020 preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. A systematic and comprehensive search was performed in several databases from inception up to 30 January 2022. The results showed that the intake of edible oil-derived MUFA (EDM) could increase the blood HDL-C level (mean difference = 0.08; 95%CI: −0.01, 0.17, p = 0.03), but did not affect the level of TC, TG, or LDL-C. Moreover, the consumption of other food-derived MUFA (ODM) significantly decreased TG concentration (mean difference = −0.35; 95%CI: −0.61, −0.09, p = 0.01)), but did not affect the level of TC, LDL-C, or HDL-C. Findings from this study suggest that MUFA-rich food might be beneficial to modulate the blood lipid profile.

Let uα,d=uα,dt,x, t∈0,T,x∈ℝd be the solution to the stochastic heat equations (SHEs) with spatially colored noise. We study the realized power variations for the process uα,d, in time, having infinite quadratic variation and dimension-dependent Gaussian asymptotic distributions. We use the underlying explicit kernels and spectral/harmonic analysis, yielding temporal central limit theorems for SHEs with spatially colored noise. This work builds on the recent works on delicate analysis of variations of general Gaussian processes and SHEs driven by space-time white noise.

Vascular inflammation and oxidative stress are the major causes of endothelial dysfunction leading to cardiovascular disease. Previously, we have reported the anti-inflammatory activity of zein hydrolysate and its-derived peptides. However, the underlying mechanisms have not been understood. In this study, we report that zein hydrolysate and its derived peptides can inhibit the tumor necrosis factor-α (TNF-α)-induced expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), the adhesion of U937 cells to EA.hy926 cells and superoxide production in EA.hy926 cells. Zein hydrolysate and its peptides also suppressed TNF-α-induced down-regulation of TNF receptor 1 (TNFR1) and phosphorylation of p65 involved in modulation of the NF-κB pathway. Our study suggests that zein hydrolysate and its derived peptides exhibited anti-inflammatory activity via preventing TNF-α induced monocyte adhesion to endothelial cells and NF-κB activation.

Abstract Background Tooth loss is suggested to be associated with an increased risk of dementia in many studies. But the relationship between tooth loss and dementia is not yet fully understood. This systematic review and meta-analysis aimed to determine the relative effect of tooth loss on dementia risk. Methods An electronic search of PubMed, Scopus, Embase, and Web of Knowledge was conducted in March 2018 to identify relevant observational studies with the English language restriction. Studies were included if they assessed the relationship between tooth loss and risk of dementia. Study quality was detected by the modified Downs and Black scale. Odds risks (ORs) were pooled using a random-effects model in the crude model. Results The literature search initially yielded 1574 articles, and 21 observational studies published between 1994 and 2017 were finally included for the analyses. The crude results with random-effects model showed that patients with multiple tooth loss had higher incidence of dementia (OR 2.62, 95% CI 1.90–3.61, P

Neurotropin (NTP) is a widely used drug in China and Japan mainly for the treatment of chronic pain and peripheral inflammation. Nevertheless, the effects of NTP on neuroinflammation have not been explored. In this study, we investigated the anti-inflammatory effects of NTP in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and its underlying mechanisms. BV-2 cells were pretreated with NTP for 12 h before exposure to LPS. The expression of pro-inflammatory cytokines (TNF-α and IL-6) were detected by RT-PCR and EILSA at mRNA and protein levels, respectively. Western blotting was conducted to measure the protein levels of major genes in MAPKs and NF-κB signaling pathways. Results demonstrated that NTP could attenuate the production of pro-inflammatory cytokines. Furthermore, NTP inhibited the activation of NF-κB signaling by decreasing the translocation of NF-κB p65 to the nucleus and suppressed the MAPKs signaling pathway via inhibition of the phosphorylation of p38, ERK and JNK. Taken together, these findings suggest that neurotropin exerts anti-inflammatory effects by suppressing the production of pro-inflammatory mediators via inhibition of NF-κB and MAPKs signaling pathways in LPS-stimulated BV-2 cells. Keywords: Neurotropin, Neuroinflammation, NF-κB, MAPKs, LPS

Alzheimer’s disease is a neurodegenerative disorder mainly characterized by β-amyloid deposit and tau hyperphosphorylation with no curative treatments. Curcumin (Cur) has been proved to have potential use in Alzheimer’s disease with its anti-amyloid, anti-inflammatory, and anti-oxidant properties, etc. However, its hydrophobicity and low bioavailability hinder its application. In this paper, we designed a novel brain-target nanoparticle, poly(lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-PEG) conjugated with B6 peptide and was loaded with Cur (PLGA-PEG-B6/Cur) and administered it into HT22 cells and APP/PS1 Al transgenic mice. The in vitro assays including dynamic light scattering (DLS), flow cytometry (FCM), red blood cell (RBC) lysis, and thromboelastography (TEG) analysis indicated that this nanoparticle could narrow the diameter of Cur, increase its cellular uptake and possess good blood compatibility. The results from Morris water maze proved that PLGA-PEG-B6/Cur could tremendously improve the spatial learning and memory capability of APP/PS1 mice, compared with native Cur. The ex vivo assays including Bielschowsky silver staining, immunostaining, and western blotting demonstrated that PLGA-PEG-B6/Cur could reduce hippocampal β-amyloid formation and deposit and tau hyperphosphorylation. Thus, we suggested that PLGA-PEG-B6/Cur nanoparticles would be of potential and promising use for the treatment of Alzheimer’s disease.

A high-performance gel permeation chromatography fluorescence detection (HPGPC-FD) method combined with fluorescein isothiocyanate (FITC) labeling was established for the microanalysis of L. barbarum polysaccharides (LBP). The calibration curves linear over the range of 0.2–20 µg/mL in rat plasma, and 0.25–500 μg/mL in urine and feces samples with correlation coefficients greater than 0.99. The inter-day and intra-day precisions (RSD, %) of the method were under 15% with the relative recovery ranging from 84.6% to 104.0% and the RSD ranging from 0.47% to 7.28%. The concentration–time curve of LBP-FITC in plasma following intragastric administration at 100, 50 and 25 mg/kg well fitted to a nonlinear model. LBP-FITC slowly eliminated from plasma according to the long half-lives (t1/2 = 31.39, 38.09, and 45.76 h, respectively) and mean retention times (MRT0–t = 18.38, 19.15 and 20.07 h, respectively; AUC0–∞ = 230.49, 236.18 and 242.57 h, respectively) after administration of LBP-FITC at doses of 100, 50, and 25 mg/kg, respectively. After intragastric administration at 50 mg/kg for 72 h, the concentration of LBP-FITC in urine and feces was 0.09 ± 0.04% and 92.18 ± 3.61% respectively; the excretion rate of urine was the highest in 0–4 h period and decreased continuously in 4–24 h period. The excretion rate of feces was the highest in 4–10 h, 48.28 ± 9.349% in feces within 4–10 h, and decreased rapidly in 10–24 h. The present study showed that LBP was absorbed as its prototype and most proportion of LBP was excreted from feces, indicating a long time remaining in intestine.

Although clinical trials of food-protein-derived peptides in the management of hypertension have been published, the results are controversial, which compelled us to conduct a meta-analysis to evaluate the pooled effect of peptide intervention. In this study, we searched for studies published between 2010 and 2021 and selected 12 eligible studies for a meta-analysis. The pooled effect of peptide intervention for systolic blood pressure (SBP) and diastolic blood pressure (DBP) was −3.28 mmHg (95% CI: −4.54, −2.03, p < 0.001) and −1.82 mmHg (95% CI: −3.46, −0.18, p = 0.03), respectively. Sub-group analyses showed that the reduction in BP in participants with higher basal BP (>140/85 mmHg) was greater (p = 0.007 for SBP and p = 0.01 for DBP), and the effect was stronger in Asian participants as compared with non-Asian participants (p = 0.01 for SBP and p = 0.04 for DBP). In addition, the effect of peptide intervention was more pronounced on SBP in participant groups with a lower ratio of male to female (≤0.5) as well as in participants with a mean age ≥50 years old. In conclusion, food-protein-derived antihypertensive peptides can significantly reduce BP in prehypertensive and hypertensive patients. Findings from this study could provide guidance for the design of clinical trials of antihypertensive peptides.

The characteristics of information flow, as represented by the Baidu index, reflect the pattern of tourism flows between different cities. This paper is based on the Baidu index and applies the seasonal concentration index and social network analysis (SNA) methods to study the spatial structure characteristics of tourism flows in China. The results reveal that: (1) both the search volume of the Baidu index in different cities and the online attention to different scenic areas exhibit obvious spatial heterogeneity and seasonal differences; (2) regions with strong tourism flow connections mainly occur in the areas between metropolises or among the inner cities of urban agglomerations, which are largely distributed on the southeast side of the Heihe–Tengchong Line; (3) the development of the whole tourism flow network in China is low, with an unbalanced development between tourism supply and demand, indicating that tourism resources are concentrated in a few cities and that most of the information interaction among cities occurs in core areas, while a weak interaction is observed in peripheral areas; (4) cities like Beijing and Wuhan attain obvious advantages in regard to their tourism resources, whereas other cities, including Beijing, Shanghai, Shenzhen and Guangzhou, exhibit a high demand for tourism. Moreover, tourism information flow networks are concentrated in several cities with an important role in the Chinese urban system, such as Beijing, Wuhan, and Chengdu, because they contain abundant tourism resources, well-developed transportation systems and advanced economic and societal development levels. (5) Cities such as Beijing, Lhasa, Wuhan, and Zhengzhou possess numerous advantages due to structural holes, and they thus occur at an advantageous position in the tourism flow network.

Metformin is the first-line pharmacotherapy for type 2 diabetes mellitus (T2D). Metformin exerts its glucose-lowering effect primarily through decreasing hepatic glucose production (HGP). However, the precise molecular mechanisms of metformin remain unclear due to supra-pharmacological concentration of metformin used in the study. Here, we investigated the role of Foxo1 in metformin action in control of glucose homeostasis and its mechanism via the transcription factor Foxo1 in mice, as well as the clinical relevance with co-treatment of aspirin. We showed that metformin inhibits HGP and blood glucose in a Foxo1-dependent manner. Furthermore, we identified that metformin suppresses glucagon-induced HGP through inhibiting the PKA→Foxo1 signaling pathway. In both cells and mice, Foxo1-S273D or A mutation abolished the suppressive effect of metformin on glucagon or fasting-induced HGP. We further showed that metformin attenuates PKA activity, decreases Foxo1-S273 phosphorylation, and improves glucose homeostasis in diet-induced obese mice. We also provided evidence that salicylate suppresses HGP and blood glucose through the PKA→Foxo1 signaling pathway, but it has no further additive improvement with metformin in control of glucose homeostasis. Our study demonstrates that metformin inhibits HGP through PKA-regulated transcription factor Foxo1 and its S273 phosphorylation.

Soy proteins are a rich source of various bioactive peptides. LSW (Leu-Ser-Trp) was previously identified from thermolysin-digested soy protein hydrolysate as a potent ACE-inhibitory peptide; however, its biological effects on vascular cells have not been elucidated. The present study evaluated anti-oxidant and anti-inflammatory activities of LSW on vascular smooth muscle cells (VSMCs). Ang II promoted oxidative stress and inflammation in VSMCs; adding LSW did not show anti-oxidant activity, while COX-2, but not iNOS, was down-regulated in Ang II-stimulated VSMCs, suggesting its anti-inflammatory activity. AT1R mediates most of the pathological effects of Ang II in VSMCs; LSW down-regulated Ang II-stimulated AT1R expression, via decreased phosphorylation of both Src and ERK1/2. Furthermore, LSW could also reduce the phosphorylation of nuclear transcription factor p50, but not p65. Results of this study suggested a novel function of LSW as an anti-inflammatory agent on VSMCs, which might broaden its uses as functional food ingredients.

Abstract Background Cytophagic histiocytic panniculitis (CHP) is a rare form of nodular panniculitis that may progress to panniculitis-like T-cell lymphoma. We report a case of CHP that first manifested as bilateral ptosis, which is the first reported case of this presentation. Case presentation A 25-year-old woman without medical history was referred to the neurology department of our hospital for evaluation of bilateral ptosis. Three months previously, she suddenly complained of bilateral ptosis without apparent cause. Simultaneously, non-painful tender subcutaneous nodules and eschar-like skin lesions were observed on her extremities and trunk. A diagnosis of CHP was made based on skin biopsy from the left thigh showing lobular panniculitis, vasculitis, and adiponecrosis, with infiltration of inflammatory cells, including lymphocytes, histiocytes, and phagocytic histiocytes. Her condition continued to worsen with corticosteroid and immunosuppressive agent (thalidomide) treatment. Significant improvement was noticed after three cycles of chemotherapy of THP-COP (pirarubicin, cyclophosphamide, vincristine, and prednisolone). Conclusions CHP is a rare condition whose clinical presentation may include bilateral ptosis and biopsy is required for diagnosis of CHP.

Hyperactivity of the Renin-Angiotensin System (RAS) is a hallmark of hypertension. Angiotensin II (AngII), the active component of RAS, not only promotes vasoconstriction but also contributes to proliferation, inflammation and oxidative stress in vascular smooth muscle cells (VSMC) that predispose to atherosclerosis. Milk derived bioactive peptides IPP (Ile-Pro-Pro) and VPP (Val-Pro-Pro) exert anti-hypertensive effects through RAS modulation. Here we evaluated the ability of these peptides to attenuate the effects of AngII on cultured VSMC. We found that VPP significantly inhibited AngII induced cell proliferation, inflammation and oxidative stress while IPP only showed anti-oxidant actions. Both peptides abolished AngII mediated activation of pro-inflammatory nuclear factor kappa B (NF-κB) pathway but only VPP could attenuate activation of extracellular signal regulated kinases (ERK) 1/2. These results demonstrate differential modulation of AngII actions on VSMC by anti-hypertensive milk peptides and indicate the potential for VPP in mitigating the vascular complications of hypertension.