A self-calibrating flexible SERS substrate incorporating PB@Au assemblies for reliable and reproducible detection.

The precise quantitative analysis using surface-enhanced Raman spectroscopy (SERS) in an uncontrollable environment still faces a significant obstacle due to the poor reproducibility of Raman signals. Herein, we propose a facile method to fabricate a self-calibrating substrate based on a flexible polyvinyl alcohol (PVA) film comprising assemblies of Prussian blue (PB) and Au NPs (PB@Au) for reliable detection. PB cores were coated with an Au shell through simple electrostatic interaction, forming core-shell nanostructure PB@Au assemblies within the PVA film. The outer Au layer provided identical trends in enhancement for both the PB core and neighboring targets while PB cores served as an internal standard (IS) to correct signal fluctuations. The prevention of competitive adsorption on the metal surface between targets and ISs was achieved. The proposed PVA/PB@Au film exhibited enhanced stability of Raman signals after IS correction, resulting in improved spot-to-spot and batch-to-batch reproducibility with significantly reduced standard deviation (RSD) values from 11.42% and 25.02% to 4.43% and 9.39%, respectively. Simultaneously, a higher accuracy in the quantitative analysis of 4-mercaptobenzoic acid (4-MBA) and malachite green (MG) was achieved with fitting coefficient (R2) values improving from 0.9675 and 0.9418 to 0.9974 and 0.9832, respectively. Moreover, the PVA/PB@Au film was successfully applied to detect residual MG in real fish samples. This work opens up an avenue to improve the reproducibility of Raman signals for flexible SERS substrates in the detection of residues under various complex conditions.

Sex Differences in the Expression of Cardiac Remodeling and Inflammatory Cytokines in Patients with Obstructive Sleep Apnea and Atrial Fibrillation.

Although there is a link between obstructive sleep apnea (OSA) and atrial fibrillation (AF) and numerous investigations have examined the mechanism of AF development in OSA patients, which includes cardiac remodeling, inflammation, and gap junction-related conduction disorder, there is limited information regarding the differences between the sexes. This study analyzes the impact of sex differences on the expression of cardiac remodeling, inflammatory cytokines, and gap junctions in patients with OSA and AF. A total of 154 individuals diagnosed with sleep-related breathing disorders (SRBDs) were enrolled in the study and underwent polysomnography and echocardiography. Significant OSA was defined as an apnea-hypopnea index (AHI) of ≥15 per hour. Exosomes were purified from the plasma of all SRBD patients and incubated in HL-1 cells to investigate their effects on inflammatory cytokines and GJA1 expression. The differences in cardiac remodeling and expression of these biomarkers in both sexes were analyzed. Of the 154 enrolled patients, 110 patients were male and 44 patients were female. The LA sizes and E/e' ratios of male OSA patients with concomitant AF were greater than those of control participants and those without AF (all p < 0.05). Meanwhile, female OSA patients with AF had a lower left ventricular ejection fraction than those OSA patients without AF and control subjects (p < 0.05). Regarding the expression of inflammatory cytokines and GJA1, the mRNA expression levels of GJA1 were lower and those of IL-1ß were higher in those male OSA patients with AF than in those male OSA patients without AF and control subjects (p < 0.05). By contrast, mRNA expression levels of HIF-1α were higher in those female OSA patients with and without AF than in control subjects (p < 0.05). In conclusion, our study revealed sex-specific differences in the risk factors and biomarkers associated with AF development in patients with OSA.

Spatial whole exome sequencing reveals the genetic features of highly-aggressive components in lung adenocarcinoma.

In invasive lung adenocarcinoma (LUAD), patients with micropapillary (MIP) or solid (SOL) components had a significantly poorer prognosis than those with only lepidic (LEP), acinar (ACI) or papillary (PAP) components. It is interesting to explore the genetic features of different histologic subtypes, especially the highly aggressive components. Based on a cohort of 5,933 patients, this study observed that in different tumor size groups, LUAD with MIP/SOL components showed a different prevalence, and patients with ALK alteration or TP53 mutations had a higher probability of developing MIP/SOL components. To control individual differences, this research used spatial whole-exome sequencing (WES) via laser-capture microdissection of five patients harboring these five coexistent components and identified genetic features among different histologic components of the same tumor. In tracing the evolution of components, we found that titin (TTN) mutation might serve as a crucial intratumor potential driver for MIP/SOL components, which was validated by a cohort of 146 LUAD patients undergoing bulk WES. Functional analysis revealed that TTN mutations enriched the complement and coagulation cascades, which correlated with the pathway of cell adhesion, migration, and proliferation. Collectively, the histologic subtypes of invasive LUAD were genetically different, and certain trunk genotypes might synergize with branching TTN mutation to develop highly aggressive components.

Effects of Smilax China L. extracts on Hyperuricemia chicken model via inhibiting xanthine oxidase activity.

Hyperuricemia (HUA) is a metabolic disorder caused by excessive production of uric acid (UA) or impaired uric acid metabolism. Smilax China L. has a wide range of pharmacological activities such as immunomodulatory, anti-inflammatory, and antioxidant. Its roots and rhizomes have been widely used for the treatment of HUA. However, its mechanisms for treating HUA and reducing renal impairment have not been fully elucidated. In the present study, we evaluated the effect of Smilax China L. extract (SC) on UA metabolism and further explored its mechanism of action by feeding a high-calcium and high-protein diet to chickens to induce a model of HUA in chickens. SC significantly reduced serum UA levels and improved renal function in hyperuricemic chickens. Meanwhile, SC was able to inhibit the activity of xanthine oxidase (XOD) in vivo and in vitro, reducing the production of uric acid. In addition, SC was able to increase the expression of Breast Cancer Resistance Protein (BCRP) in the kidney and ileum and increase uric acid excretion. Therefore, our results suggest that SC may be a candidate for anti-hyperuricemia.

Celastrol alleviates diabetic vascular injury via Keap1/Nrf2-mediated anti-inflammation.

Introduction: Celastrol (Cel) is a widely used main component of Chinese herbal medicine with strong anti-inflammatory, antiviral and antitumor activities. In the present study, we aimed to elucidate the cellular molecular protective mechanism of Cel against diabetes-induced inflammation and endothelial dysfunction. Methods: Type 2 diabetes (T2DM) was induced by db/db mice, and osmotic pumps containing Cel (100 µg/kg/day) were implanted intraperitoneally and were calibrated to release the drug for 28 days. In addition, human umbilical vein endothelial cells (HUVECs) were cultured in normal or high glucose and palmitic acid-containing (HG + PA) media in the presence or absence of Cel for 48 h. Results: Cel significantly ameliorated the hyperglycemia-induced abnormalities in nuclear factor (erythroid-derived 2)-like protein 2 (Nrf2) pathway activity and alleviated HG + PA-induced oxidative damage. However, the protective effect of Cel was almost completely abolished in HUVECs transfected with short hairpin (sh)RNA targeting Nrf2, but not by nonsense shRNA. Furthermore, HG + PA reduced the phosphorylation of AMP-activated protein kinase (AMPK), the autophagic degradation of p62/Kelch-like ECH-associated protein 1 (Keap1), and the nuclear localization of Nrf2. However, these catabolic pathways were inhibited by Cel treatment in HUVECs. In addition, compound C (AMPK inhibitors) and AAV9-sh-Nrf2 reduced Cel-induced Nrf2 activation and angiogenesis in db/db mice. Discussion: Taking these findings together, the endothelial protective effect of Cel in the presence of HG + PA may be at least in part attributed to its effects to reduce reactive oxygen species (ROS) and inflammation through p62/Keap1-mediated Nrf2 activation.

Sensitive SERS assay for L-cysteine based on functionalized silver nanoparticles.

L-cysteine, an indispensable amino acid present in natural proteins, plays pivotal roles in various biological processes. Consequently, precise and selective monitoring of its concentrations is imperative. Herein, we propose a Surface-enhanced Raman Scattering (SERS) sensor for detecting L-cysteine based on the anti-aggregation of 4-mercaptobenzoic acid (4-MBA) and histidine (His) functionalized silver nanoparticles (Ag NPs). The presence of Hg2+ ions can induce the aggregation of Ag NPs@His@4-MBA due to the unique nanostructures of Ag NPs@His@4-MBA, resulting in a robust SERS intensity of 4-MBA. However, in the presence of L-cysteine, the stronger affinity between L-cysteine and Hg2+ reduces the concentration of free Hg2+, causing the dispersion of the aggregated functionalized Ag NPs and the reduction of the SERS signal intensity of 4-MBA. The developed SERS platform demonstrates excellent performance with a low detection limit of 5 nM (S/N = 3) and linear detection capabilities within the range of 0.01-100 µM for L-cysteine. Additionally, the method was successfully employed for the determination of L-cysteine in spiked serum samples, yielding recoveries ranging from 95.0 % to 108.1 % with relative standard deviations of less than 3.3 %. This study not only presents a novel approach for fabricating highly sensitive and specific SERS biosensors for biomolecule detection but also offers a significant strategy for the development and construction of SERS substrates using anti-aggregation design.

The impact of PET/CT and brain MRI for metastasis detection among patients with clinical T1-category lung cancer: Findings from a large-scale cohort study.

PURPOSE: [18F]-FDG PET/CT and brain MRI are common approaches to detect metastasis in patients of lung cancer. Current guidelines for the use of PET/CT and MRI in clinical T1-category lung cancer lack risk-based stratification and require optimization. This study stratified patients based on metastatic risk in terms of the lesions' size and morphological characteristics. METHODS: The detection rate of metastasis was measured in different sizes and morphological characteristics (solid and sub-solid) of tumors. To confirm the cut-off value for discriminating metastasis and overall survival (OS) prediction, the receiver operating characteristic (ROC) analysis was performed based on PET/CT metabolic parameters (SUVmax/SUVmean/SULpeak/MTV/TLG), followed by Kaplan-Meier analysis for survival in post-operation patients with and without PET/CT plus MRI. RESULTS: 2,298 patients were included. No metastasis was observed in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm. The cut-off of PET/CT metabolic parameters on discriminating metastasis were 1.09 (SUVmax), 0.26 (SUVmean), 0.31 (SULpeak), 0.55 (MTV), and 0.81 (TLG), respectively. Patients undergoing PET/CT plus MRI exhibited longer OS compared to those who did not receive it in solid nodules ≥ 8.0 mm & sub-solid nodules ≥ 10.0 mm (HR, 0.44; p < 0.001); in solid nodules ≥ 8.0 mm (HR, 0.12; p<0.001) and in sub-solid nodules ≥ 10.0 mm (HR; 0.61; p=0.075), respectively. Compared to patients with metabolic parameters lower than cut-off values, patients with higher metabolic parameters displayed shorter OS: SUVmax (HR, 12.94; p < 0.001), SUVmean (HR, 11.33; p <0.001), SULpeak (HR, 9.65; p < 0.001), MTV (HR, 9.16; p = 0.031), and TLG (HR, 12.06; p < 0.001). CONCLUSION: The necessity of PET/CT and MRI should be cautiously evaluated in patients with solid nodules < 8.0 mm and sub-solid nodules < 10.0 mm, however, these examinations remained essential and beneficial for patients with solid nodules ≥ 8.0 mm and sub-solid nodules ≥ 10.0 mm.

Screening and validation of atherosclerosis PAN-apoptotic immune-related genes based on single-cell sequencing.

Background: Carotid atherosclerosis (CAS) is a complication of atherosclerosis (AS). PAN-optosome is an inflammatory programmed cell death pathway event regulated by the PAN-optosome complex. CAS's PAN-optosome-related genes (PORGs) have yet to be studied. Hence, screening the PAN-optosome-related diagnostic genes for treating CAS was vital. Methods: We introduced transcriptome data to screen out differentially expressed genes (DEGs) in CAS. Subsequently, WGCNA analysis was utilized to mine module genes about PANoptosis score. We performed differential expression analysis (CAS samples vs. standard samples) to obtain CAS-related differentially expressed genes at the single-cell level. Venn diagram was executed to identify PAN-optosome-related differential genes (POR-DEGs) associated with CAS. Further, LASSO regression and RF algorithm were implemented to were executed to build a diagnostic model. We additionally performed immune infiltration and gene set enrichment analysis (GSEA) based on diagnostic genes. We verified the accuracy of the model genes by single-cell nuclear sequencing and RT-qPCR validation of clinical samples, as well as in vitro cellular experiments. Results: We identified 785 DEGs associated with CAS. Then, 4296 module genes about PANoptosis score were obtained. We obtained the 7365 and 1631 CAS-related DEGs at the single-cell level, respectively. 67 POR-DEGs were retained Venn diagram. Subsequently, 4 PAN-optosome-related diagnostic genes (CNTN4, FILIP1, PHGDH, and TFPI2) were identified via machine learning. Cellular function tests on four genes showed that these genes have essential roles in maintaining arterial cell viability and resisting cellular senescence. Conclusion: We obtained four PANoptosis-related diagnostic genes (CNTN4, FILIP1, PHGDH, and TFPI2) associated with CAS, laying a theoretical foundation for treating CAS.

Poly(ionic liquid)s-Based Thermal-Responsive Microgel for Use as SERS Substrates with "ON-OFF" Switchable Effect.

A temperature-responsive surface-enhanced Raman scattering (SERS) substrate with "ON-OFF" switching based on poly(ionic liquid)s (PILs) block copolymer microgels have been designed and synthesized. The PIL units act as a joint component to anchor the gold nanoparticles (AuNPs) and analytes onto poly(N-isopropylacrylamide) (PNIPAm). This anchor allows the analytes to be fixed at the formed hot spots under temperature stimulus. Owing to the regulation of the PNIPAm segment, the SERS substrates exhibit excellent thermally responsive SERS activity with a reversible "ON-OFF" effect. Additionally, because of the anion exchange of PILs, microgels can introduce new analytes, which offers more flexibility for the system. The substrate shows excellent reversibility, controllability, and flexibility of SERS activity, which is expected to have a broad application in the field of practical SERS sensors.

New Diterpenes and Diterpene Glycosides with Antibacterial Activity from Soft Coral Lemnalia bournei.

Five new biflorane-type diterpenoids, biofloranates E-I (1-5), and two new bicyclic diterpene glycosides, lemnaboursides H-I (6-7), along with the known lemnabourside, were isolated from the South China Sea soft coral Lemnalia bournei. Their chemical structures and stereochemistry were determined based on extensive spectroscopic methods, including time-dependent density functional theory (TDDFT) ECD calculations, as well as a comparison of them with the reported values. The antibacterial activities of the isolated compounds were evaluated against five pathogenic bacteria, and all of these diterpenes and diterpene glycosides showed antibacterial activities against Staphylococcus aureus and Bacillus subtilis, with MICs ranging from 4 to 64 µg/mL. In addition, these compounds did not exhibit noticeable cytotoxicities on A549, Hela, and HepG2 cancer cell lines, at 20 µM.

Using a visual support package to facilitate independent leisure engagement and choice-making for individuals with moderate to severe autism in Taiwan.

LAY ABSTRACT: Self-determination encompasses various components, including decision-making and independence, making it a complex process. While the importance of self-determination for individuals with autism spectrum disorder has been explored in previous studies, there is limited research focusing on individuals with moderate to severe autism spectrum disorder. Evidence-based practices such as visual activity schedules and video modeling have shown effectiveness in promoting independence among individuals with autism spectrum disorder. To address the need for independence and choice-making among individuals with moderate to severe autism spectrum disorder, this study developed a visual support package incorporating visual activity schedules, video modeling, preference assessments, and prompt procedures. By investigating the intervention's effectiveness in three participants, this study contributes to the existing literature on the use of a visual activity schedule and video modeling in enhancing choice-making and independent leisure engagement. Following the intervention, all participants were able to select three leisure activities, develop their own visual schedules, and complete them. Notably, this study conducted preference assessments to determine participants' preferred leisure activities and did not provide additional reinforcement. Practical implications of this research include incorporating video prompting as needed and adjusting activity engagement time. Future research should explore the long-term effectiveness of the visual support package and its application in developing novel skills or vocational activities for individuals with moderate to severe autism spectrum disorder. This study fills a critical gap in the literature, providing important insights for practices and research in the field of autism spectrum disorder interventions.

Genome-wide identification of GATA transcription factors in tetraploid potato and expression analysis in differently colored potato flesh.

The GATA gene family belongs to a kind of transcriptional regulatory protein featuring a zinc finger motif, which is essential for plant growth and development. However, the identification of the GATA gene family in tetraploid potato is still not performed. In the present research, a total of 88 GATA genes in the tetraploid potato C88.v1 genome were identified by bioinformatics methods. These StGATA genes had an uneven distribution on 44 chromosomes, and the corresponding StGATA proteins were divided into four subfamilies (I-IV) based on phylogenetic analysis. The cis-elements of StGATA genes were identified, including multiple cis-elements related to light-responsive and hormone-responsive. The collinearity analysis indicates that segmental duplication is a key driving force for the expansion of GATA gene family in tetraploid potato, and that the GATA gene families of tetraploid potato and Arabidopsis share a closer evolutionary relationship than rice. The transcript profiling analysis showed that all 88 StGATA genes had tissue-specific expression, indicating that the StGATA gene family members participate in the development of multiple potato tissues. The RNA-seq analysis was also performed on the tuber flesh of two potato varieties with different color, and 18 differentially expressed GATA transcription factor genes were screened, of which eight genes were validated through qRT-PCR. In this study, we identified and characterized StGATA transcription factors in tetraploid potato for the first time, and screened differentially expressed genes in potato flesh with different color. It provides a theoretical basis for further understanding the StGATA gene family and its function in anthocyanin biosynthesis.

In-depth understanding of the effects of different molecular weight pullulan interacting with protein and starch on dough structure and application properties.

This work clarified the positive effects of pullulan on dough structure and application properties varied with its molecular weight. Pullulan with different molecular weights were introduced into dough system to explore their intervention effects on structural and technological properties of dough as well as physical and digestion properties of biscuits. Results showed that HPL (pullulan with molecule weight of 100- 300 kDa) could increase the intermolecular collisions, prompt the protein aggregation and limit the water migration in dough system, resulting in an integrate, continuous and dense network structure of the gel with strengthened elasticity and weakened extensibility, which caused an increase in biscuit thickness, hardness and crispness. On the contrary, LPL (pullulan with molecule weight of 3- 100 kDa) could go against the formation of stable and elastic dough through breaking down cross-linkage between protein and starch so as to provide biscuits with decreased hardness and crispness during baking. Both HPL and LPL delayed starch pasting and retrogradation process while HPL had the stronger retarding effect on starch digestibility of biscuits than LPL. These findings dedicated to a better understanding of pullulan function in dough system and provide suggestions for fractionation applications of pullulan in food field.

A Degree-Dependent Polynomial-Based Reciprocally Convex Matrix Inequality and Its Application to Stability Analysis of Delayed Neural Networks.

In this article, several improved stability criteria for time-varying delayed neural networks (DNNs) are proposed. A degree-dependent polynomial-based reciprocally convex matrix inequality (RCMI) is proposed for obtaining less conservative stability criteria. Unlike previous RCMIs, the matrix inequality in this article produces a polynomial of any degree in the time-varying delay, which helps to reduce conservatism. In addition, to reduce the computational complexity caused by dealing with the negative definite of the high-degree terms, an improved lemma is presented. Applying the above matrix inequalities and improved negative definiteness condition helps to generate a more relaxed stability criterion for analyzing time-varying DNNs. Two examples are provided to illustrate this statement.

Differential methylation patterns from clusters associated with glucose metabolism: evidence from a Shanghai twin study.

Aim: To assess the associations between genome-wide DNA methylation (DNAm) and glucose metabolism among a Chinese population, in particular the multisite correlation. Materials & methods: Epigenome-wide associations with fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) were analyzed among 100 Shanghai monozygotic (MZ) twin pairs using the Infinium HumanMethylationEPIC v2.0 BeadChip. We conducted a Pearson's correlation test, hierarchical cluster and pairwise analysis to examine the differential methylation patterns from clusters. Results: Cg01358804 (TXNIP) was identified as the most significant site associated with FPG and HbA1c. Two clusters with hypermethylated and hypomethylated patterns were observed for both FPG and HbA1c. Conclusion: Differential methylation patterns from clusters may provide new clues for epigenetic changes and biological mechanisms in glucose metabolism.

Sleep quality assessment of adults in care settings using non-wearable sleep trackers: Scoping review.

AIMS: This review aimed to explore and map the literature on sleep quality assessments of adults in care settings using non-wearable sleep trackers. BACKGROUND: Sleep-monitoring technology is advancing, and sleep quality assessments using non-wearable sleep trackers can provide objective evidence for quality care. DESIGN: This was a scoping review. DATA SOURCES: Four electronic databases (PubMed, CINAHL, PsycInfo and Embase) were searched on 23 September 2022. REVIEW METHODS: This review followed the Joanna Briggs Institute's methodology and used the PRISMA-ScR checklist. RESULTS: Thirty studies met our inclusion criteria. Sleep quality was assessed at home and in acute, non-acute and long-term care facilities. Physiological (heart rate and respiratory rate) and sleep parameters were assessed alone or in combination during patient care using non-wearable sleep trackers. Sleep parameters representing sleep quality varied across studies. Real-time monitoring with non-wearable sleep-tracking devices effectively shortened the length of hospital stay. However, studies investigating caregivers and nursing outcomes are lacking in the literature. CONCLUSION: Sleep quality assessments using non-wearable sleep trackers may facilitate the provision of quality care in home-based and clinical care settings. Future studies should focus on caregivers and care outcomes that could contribute to evidence-based nursing practice for sleep care in adults.

Effects of Ban Lian Zi Jin San on intestinal inflammation and barrier function of heat-stressed broilers.

Heat stress (HS) in broilers can be an environmental stressor that leads to intestinal inflammation and intestinal barrier damage. In order to examine the effect of Ban Lian Zi Jin San (BLZJS) on intestinal inflammation and barrier function in heat-stressed broilers, a model of chronic cyclic HS in broilers was established. A total of 300 twenty-one-day-old broilers were divided into 5 treatments at random. Broilers in 3 BLZJS dosage groups were kept in an ecologically controlled room at 37℃ ± 2℃ for 6 wk, and fed basal diets supplemented with 0.5, 1, and 2% BLZJS. Broilers in HS group were housed in the same room, but fed the basal diets. The findings indicated that supplementation of BLZJS significantly declined serum HS indexes levels (HSP70, HSP90), and increased serum antioxidant capacity (SOD and T-AOC) in broilers (P < 0.05). Besides, supplementation of BLZJS significantly inhibited the expression of HS indexes (HSP70 and HSP90), genes related to TLR4 inflammatory signal pathway (TLR4, MyD88, TRIF, IRAK-4, and NF-κB), inflammatory factors (IL-6 and TNF-α), and upregulated anti-inflammatory cytokines (IL-10) and intestinal tight junction-related genes (Occludin, Claudin-1, and ZO-1) in broiler jejunum (P < 0.05). On the other hand, supplementation of BLZJS could significantly reduce the protein expression of NF-κB and HSP70 in chick jejunum (P < 0.05). In conclusion, BLZJS inhibited the activation of TLR4 signal pathway and reduced the production of inflammatory factors, restoring the level of intestinal tight junction protein and protecting jejunal intestinal barrier function in heat-stressed broilers.

Dietary Macronutrient Intake and Cardiovascular Disease Risk and Mortality: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.

Many epidemiological studies have evaluated the intake of macronutrients and the risk of mortality and cardiovascular disease (CVD). However, current evidence is conflicting and warrants further investigation. Therefore, we carried out an umbrella review to examine and quantify the potential dose-response association of dietary macronutrient intake with CVD morbidity and mortality. Prospective cohort studies from PubMed, Embase, and CENTRAL were reviewed, which reported associations of macronutrients (protein, fat, and carbohydrate) with all-cause, CVD, cancer mortality, or CVD events. Multivariable relative risks (RR) were pooled, and heterogeneity was assessed. The results of 124 prospective cohort studies were included in the systematic review and 101 in the meta-analysis. During the follow-up period from 2.2 to 30 years, 506,086 deaths and 79,585 CVD events occurred among 5,107,821 participants. High total protein intake was associated with low CVD morbidity (RR 0.88, 95% confidence interval 0.82-0.94), while high total carbohydrate intake was associated with high CVD morbidity (1.08, 1.02-1.13). For fats, a high intake of total fat was associated with a decreased all-cause mortality risk (0.92, 0.85-0.99). Saturated fatty acid intake was only associated with cancer mortality (1.10, 1.06-1.14); Both monounsaturated fatty acid (MUFA) and polyunsaturated fatty acids (PUFA) intake was associated with all-cause mortality (MUFA: 0.92, 0.86-0.98; PUFA: 0.91, 0.86-0.96). This meta-analysis supports that protein intake is associated with a decreased risk of CVD morbidity, while carbohydrate intake is associated with an increased risk of CVD morbidity. High total fat intake is associated with a low risk of all-cause mortality, and this effect was different in an analysis stratified by the type of fat.

Peanut oil odor enhances the immunomodulatory effect on immunosuppressed mice by regulating the cAMP signaling pathway via the brain-spleen axis.

The role of sniffing relative to immune function has attracted considerable attention. The present study investigated the immunomodulatory effects of peanut oil odor on cyclophosphamide (CTX)-induced immunosuppressed mice. The subset of mice subjected to prolonged (8 h) sniffing peanut oil odor (PL) demonstrated significantly elevated levels of agouti-related peptide, neuropeptide Y, and glutamate (p < 0.05), whereas it significantly down-regulated the level of γ-aminobutyric acid in the brain (p < 0.05). Furthermore, immunohistochemistry results indicated significantly increased expression of mGluR1/5 and decreased expression of GABABR in the hippocampus and hypothalamus (p < 0.05) of the PL group. Additionally, the PL group had significantly up-regulated expression levels of cAMP, Epac, Rap1, ERK1/2 and PKA (p < 0.05) and remarkably increased phosphorylation of CREB in the cAMP signaling pathway (p < 0.05), which influenced the central nervous system. Moreover, compared with CTX-induced mice, the percentages of peripheral blood T lymphocytes (CD3+CD4+ and CD3+CD8+) and the levels of splenic cytokines (IL-2, IL-4, and TNF-α) were significantly increased following PL treatment (p < 0.05). The PL group also showed significantly up-regulated expression levels of cAMP, p-p65, and p-IκBα in the spleen (p < 0.05) by western blot analysis. In summary, PL intervention significantly up-regulated the expression levels of cAMP in the brain (p < 0.05), with subsequent transfer of cAMP to the spleen which promoted phosphorylation of p65 and IκBα. This series of events enhanced the immunity of mice, which confirmed the regulatory effect of PL on the cAMP signaling pathway, thereby enhancing immune function via the brain-spleen axis.