Fucoidan prevents diabetic cognitive dysfunction via promoting TET2-mediated active DNA demethylation in high-fat diet induced diabetic mice.

Diabetic cognitive dysfunction (DCD) refers to cognitive impairment in individuals with diabetes, which is one of the most important comorbidities and complications. Preliminary evidence suggests that consuming sufficient dietary fiber could have benefits for both diabetes and cognitive function. However, the effect and underlying mechanism of dietary fiber on DCD remain unclear. We conducted a cross-sectional analysis using data from NHANES involving 2072 diabetics and indicated a significant positive dose-response relationship between the dietary fiber intake and cognitive performance in diabetics. Furthermore, we observed disrupted cognitive function and neuronal morphology in high-fat diet induced DCD mice, both of which were effectively restored by fucoidan supplementation through alleviating DNA epigenetic metabolic disorders. Moreover, fucoidan supplementation enhanced the levels of short-chain fatty acids (SCFAs) in the cecum of diabetic mice. These SCFAs enhanced TET2 protein stability by activating phosphorylated AMPK and improved TETs activity by reducing the ratio of (succinic acid + fumaric acid)/ α-ketoglutaric acid, subsequently enhancing TET2 function. The positive correlation between dietary fiber intake and cognitive function in diabetics was supported by human and animal studies alike. Importantly, fucoidan can prevent the occurrence of DCD by promoting TET2-mediated active DNA demethylation in the cerebral cortex of diabetic mice.

Fucoidan Improves Early Stage Diabetic Nephropathy via the Gut Microbiota-Mitochondria Axis in High-Fat Diet-Induced Diabetic Mice.

Diabetic nephropathy (DN) is a common microvascular complication of diabetes. Fucoidan, a polysaccharide containing fucose and sulfate group, ameliorates DN. However, the underlying mechanism has not been fully understood. This study aimed to explore the effects and mechanism of fucoidan on DN in high-fat diet-induced diabetic mice. A total of 90 C57BL/6J mice were randomly assigned to six groups (n = 15) as follows: normal control (NC), diabetes mellitus (DM), metformin (MTF), low-dose fucoidan (LFC), medium-dose fucoidan (MFC), and high-dose fucoidan (HFC). A technique based on fluorescein isothiocyanate (FITC-sinistin) elimination kinetics measured percutaneously was applied to determine the glomerular filtration rate (GFR). After 24 weeks, the mice were sacrificed and an early stage DN model was confirmed by GFR hyperfiltration, elevated urinary creatinine, normal urinary albumin, tubulointerstitial fibrosis, and glomerular hypertrophy. Fucoidan significantly improved the GFR hyperfiltration and renal fibrosis. An enriched SCFAs-producing bacteria and increased acetic concentration in cecum contents were found in fucoidan groups, as well as increased renal ATP levels and improved mitochondrial dysfunction. The renal inflammation and fibrosis were ameliorated through inhibiting the MAPKs pathway. In conclusion, fucoidan improved early stage DN targeting the microbiota-mitochondria axis by ameliorating mitochondrial oxidative stress and inhibiting the MAPKs pathway.

A Comprehensive Overview of Micro-Influencer Marketing: Decoding the Current Landscape, Impacts, and Trends.

This research provides a comprehensive overview of micro-influence marketing, analyzing the characteristics of influencers and the mechanisms of their impact. A systematic review was conducted, encompassing 2091 citing articles and references across 74 studies involving 95 research institutions and over 12,000 samples. Employing an interdisciplinary approach that integrates insights from computer science, information science, communication, culture, psychology, sociology, education, business, and management, this study outlines the distinct features of micro-influencers. These features include performable authenticity, affinity expressed through consistency and transparency, musical and artistic media talent, and competitive individual traits. The research synthesizes antecedents of trust and attachment mechanisms commonly employed in influencer theory, taking an objective standpoint and minimizing emphasis on audience engagement and perception to trigger influence. The findings highlight that followers' pursuit of self-branding, driven by self-consciousness, social consciousness, credibility, and social presence, significantly influences the impact of self-expressive products on the audience's purchase intention. The research contributes to micro-influence marketing theory by integrating mechanics, offering practical implications for micro-influencers, and suggesting future research agendas.

The collaborative mode by PmSVPs and PmDAMs reveals neofunctionalization in the switch of the flower bud development and dormancy for Prunus mume.

Prunus mume (Rosaceae, Prunoideae) serves as an excellent ornamental woody plant with a large-temperature-range cultivation scope. Its flower buds require a certain low temperature to achieve flowering circulation. Thus, it is important to delve into the processes of flower bud differentiation and dormancy, which affected its continuous flowering. These processes are generally considered as regulation by the MADS-box homologs, SHORT VEGETATIVE PHASE (SVP), and DORMANCY-ASSOCIATED MADS-BOX (DAM). However, a precise model on their interdependence and specific function, when acting as a complex in the flower development of P. mume, is needed. Therefore, this study highlighted the integral roles of PmDAMs and PmSVPs in flower organ development and dormancy cycle. The segregation of PmDAMs and PmSVPs in a different cluster suggested distinct functions and neofunctionalization. The expression pattern and yeast two-hybrid assays jointly revealed that eight genes were involved in the floral organ development stages, with PmDAM1 and PmDAM5 specifically related to prolificated flower formation. PmSVP1-2 mingled in the protein complex in bud dormancy stages with PmDAMs. Finally, we proposed the hypothesis that PmSVP1 and PmSVP2 could combine with PmDAM1 to have an effect on flower organogenesis and interact with PmDAM5 and PmDAM6 to regulate flower bud dormancy. These findings could help expand the current molecular mechanism based on MADS-box genes during flower bud development and dormancy.

The complete chloroplast sequence of phalaenopsis malipoensis, a rare orchidaceae species in China.

Phalaenopsis malipoensis Z.J. Liu et S.C. Chen, 2005 is a valuable species of Orchidaceae with significant ornamental value. This study reports the first complete chloroplast genome of P.malipoensis was collected integrally and clarified further. The genome was 144,528 bp in length and comprised four regions, including a pair of inverted repeats each 24,710 bp, a large single-copy region of 83,475 bp, and a small single-copy region of 11,633 bp. The whole genome contained 125 genes, including 8 rRNAs, and 39 tRNAs. Phylogenetic analysis indicated that P. malipoensis was closely related to Phalaenopsis lobbii. The analysis of P. malipoensis chloroplast genome will provide significant data for the identification and further improvement of P. malipoensis.

Dietary pattern characterized by a balanced diet rich in high-quality protein intake is associated with mild initial clinical manifestations in tuberculosis.

Background: The relationship between a single food or nutrient and pulmonary tuberculosis (TB) has been explored in many studies; however, the relationship between dietary patterns and TB is still lacking. Objective: Our study aims to investigate the association between dietary patterns and the initial clinical manifestations in patients with TB. Materials and methods: A cross-sectional study including 1,661 patients with active TB was conducted in Qingdao, China, from 2011 to 2019. A semiquantitative food frequency questionnaire was used to collect dietary data. Dietary patterns were determined by principal component factor analysis. Initial clinical manifestations were assessed using a combination of the patient self-reported clinical symptoms and the admission results indicated by the TB score. The associations between dietary patterns and TB scores in patients with TB were examined by the logistics regression model. Results: The analysis identified four dietary patterns: meat-fruit-seafood pattern; dairy-egg pattern; beans and their products-whole grain pattern; and refined grain-vegetable pattern. In a multiple-adjusted model, higher adherence to the meat-fruit-seafood pattern showed a protective effect on the TB score (OR 0.53, 95% CI 0.39, 0.84, P for trend = 0.010) and the association was stronger in patients older than 45 years (OR 0.32, 95% CI 0.16, 0.64, P for trend < 0.001). The higher adherence to beans and their products-whole grain pattern was a protective factor for TB score (OR 0.57, 95% CI 0.37, 0.87, P for trend = 0.025), and the association was also observed in patients with concurrent TB and diabetes mellitus (DM) with a more significant effect (OR 0.33, 95% CI 0.14, 0.80, P for trend = 0.025). No significant association was found between dairy-egg pattern and refined grain-vegetable dietary pattern with TB score. Conclusion: Dietary patterns characterized by a balanced diet rich in high-quality protein, sufficient energy, as well as marine n-3 PUFA, phytochemicals, B vitamins, and fiber are associated with mild initial clinical manifestations, and the association is stronger in patients older than 45 years and those with concurrent TB and DM.

Minimal EEG channel selection for depression detection with connectivity features during sleep.

BACKGROUND AND OBJECTIVES: Sleeping cortical electroencephalogram (EEG) has the potential for depression detection, for different sleep structure and cortical connection have been proved in depressed patients. However, the operation of multi-channel sleep EEG recording is cumbersome and requires laboratory equipment and professional sleep technician. Here, we focus on the depression detection using minimal sleep EEG channels. METHODS: Sixteen channels of EEG data of 30 patients with depression and 30 age-matched normal controls were recorded during sleep. Power spectral density of each single EEG channel was calculated, followed by measuring the symbolic transfer entropy (STE) and weighed phase lag index (WPLI) between EEG channel pairs in various frequency bands. Thereafter, these features were evaluated by F-score in the two-way classification (depression vs. control) of 30-s sleep EEG segments. Based on the F-score, entropy method was introduced to calculate the weight which could further assess the classification ability of various EEG channels or channel pairs. Finally, machine learning was implemented to verify the important EEG channels or channel pairs in depression diagnosis. RESULTS: The features characterizing the inter-hemispheric connectivity in the posterior lobe, especially in the temporal lobe, showed high classification capacity. The classification accuracy of using two and four EEG channels in the temporal lobe were 97.96% and 99.61%, respectively. CONCLUSIONS: This study showed the possibility of using only a few sleep EEG channels for depression screening, which may greatly facilitate the diagnosis of depression outside the hospital.

Associations between cortical activation and network interaction during sleep.

Cortical activation and network interaction, two characterizations of the cortical states, are separately studied in most previous studies. To further clarify the underlying mechanism, the association between these two indicators during sleep was investigated in this study. Twenty healthy individuals were enrolled and all of them underwent overnight polysomnography (PSG) recording. The relative spectral powers and the phase transfer entropy (PTE) of various frequency components were extracted from 6 electroencephalographic (EEG) channels, to assess the cortical activation and network interaction, respectively. Pearson correlation coefficient was employed to estimate their associations. The results suggested that there was a negative correlation between spectral power and phase transfer entropy in δ and α frequency bands during sleep. As the sleep deepened, an increased negative correlation in the δ frequency band was noted, but the negative correlation became less extreme in the α frequency band. The extremum of the correlation coefficient was noted in δ of N3, and α of Wake. Overall, this study provides a connection between these two cortical activity assessments, especially reveals the variable characteristics of different frequency components, which is conducive to better understand sleep state.

5-Hydroxymethylcytosine Signatures in Circulating Cell-Free DNA as Diagnostic Biomarkers for Late-Onset Alzheimer's Disease.

BACKGROUND: 5-Hydroxymethylcytosine (5hmC) is an epigenetic DNA modification that is highly abundant in central nervous system. It has been reported that DNA 5hmC dysregulation play a critical role in Alzheimer's disease (AD) pathology. Changes in 5hmC signatures can be detected in circulating cell-free DNA (cfDNA), which has shown potential as a non-invasive liquid biopsy material. OBJECTIVE: However, the genome-wide profiling of 5hmC in cfDNA and its potential for the diagnosis of AD has not been reported to date. METHODS: We carried out a case-control study and used a genome-wide chemical capture followed by high-throughput sequencing to detect the genome-wide profiles of 5hmC in human cfDNA and identified differentially hydroxymethylated regions (DhMRs) in late-onset AD patients and the control. RESULTS: We discovered significant differences of 5hmC enrichment in gene bodies which were linked to multiple AD pathogenesis-associated signaling pathways in AD patients compared with cognitively normal controls, indicating they can be well distinguished from normal controls by DhMRs in cfDNA. Specially, we identified 7 distinct genes (RABEP1, CPNE4, DNAJC15, REEP3, ROR1, CAMK1D, and RBFOX1) with predicting diagnostic potential based on their significant correlations with MMSE and MoCA scores of subjects. CONCLUSION: The present results suggest that 5hmC markers derived from plasma cfDNA can served as an effective, minimally invasive biomarkers for clinical auxiliary diagnosis of late-onset AD.

Joint effect of 25-hydroxyvitamin D and secondhand smoke exposure on hypertension in non-smoking women of childbearing age: NHANES 2007-2014.

BACKGROUND: Vitamin D deficiency (VDD) may increase the risk of hypertension in women of childbearing age, who may be exposed to secondhand smoke (SHS) simultaneously. Till now, few studies have investigated the joint effects of VDD and SHS on hypertension in this population. We evaluated whether exposure to SHS modified the association between VDD and hypertension. METHODS: Data from National Health and Nutrition Examination Surveys (NHANES) 2007-2014 were analyzed. Our research subjects were 2826 nonsmoking and nonpregnant women of childbearing age (20-44 years old). Hypertension was defined based either on systolic blood pressure (SBP) ≥ 130 mmHg and/or diastolic blood pressure (DBP) ≥ 80 mmHg or on now taking prescribed medicine for hypertension. The directed acyclic graphs (DAG) and the back-door criterion were used to select a minimal sufficient adjustment set of variables (MSAs) that would identify the unconfounded effect of 25(OH)D and hypertension. The interactive effect of VDD and SHS on hypertension was evaluated by using logistic regression models, followed by strata-specific analyses. RESULTS: The prevalence of VDD in the hypertension group was significantly higher than that in the non-hypertension group (48.2% vs 41.0%, P = 0.008), as well as the exposure rate of SHS (39.1% vs 33.8%, P = 0.017). VDD was independently associated with nearly 50% increased risk of hypertension [adjusted odds ratio (aOR) = 1.43, 95% confidence interval (CI): 1.01, 2.04], while no significant association was observed between SHS and hypertension. However, SHS showed a significant synergistic effect on VDD with a higher aOR of 1.79 (95% CI: 1.14, 2.80) (Pinteraction = 0.011). This synergistic effect was more obvious when stratified by BMI (in overweight women, aOR, 95% CI =4.74, 1.65-13.60 for interaction vs 2.33, 1.01-5.38 for VDD only) and race (in Non-Hispanic Black women, aOR, 95% CI =5.11, 1.58-16.54 for interaction vs 2.69, 1.10-6.62 for VDD only). CONCLUSION: There exist synergistic effects of SHS and VDD on the prevalence of hypertension in American women of childbearing age, with more significant effects in women who were overweight or Non-Hispanic Black. Further studies are warranted to verify this finding in other populations, and the molecular mechanisms underlying the joint effect of SHS and VDD need to be elucidated.

Characterization of specific spatial functional connectivity difference in depression during sleep.

Depression is a common mental illness and a large number of researchers have been still devoted to exploring effective biomarkers for the identification of depression. Few researches have been conducted on functional connectivity (FC) during sleep in depression. In this paper, a novel depression characterization is proposed using specific spatial FC features of sleep electroencephalography (EEG). Overnight polysomnography recordings were obtained from 26 healthy individuals and 25 patients with depression. The weighted phase lag indexes (WPLIs) of four frequency bands and five sleep periods were obtained from 16 EEG channels. The high discriminative connections extracted via feature evaluation and the cross-within variation (CW)-the spatial feature constructed to characterize the different performances in inter- and intra-hemispheric FC based on WPLIs, were utilized to classify patients and normal controls. The results showed that enhanced average FC and spatial differences, higher inter-hemispheric FC and lower intra-hemispheric FC, were found in patients. Furthermore, abnormalities in the inter-hemispheric connections of the temporal lobe in the theta band should be important indicators of depression. Finally, both CW and high discriminative WPLI features performed well in depression screening and CW was more specific for characterizing abnormal cortical EEG performance of depression. Our work investigated and characterized the abnormalities in sleep cortical activity in patients with depression, and may provide potential biomarkers for assisting with depression identification and new insights into the understanding of pathological mechanisms in depression.

Dibromoacetic acid induced Cl.Ly1+2/-9 T-cell apoptosis and activation of MAPKs signaling cascades.

Dibromoacetic acid (DBA), a haloacetic acid by-product of disinfection of drinking water, can cause many adverse effects in test animals, including immunotoxicity. However, the underlying molecular mechanism for the immunomodulatory effects remains unclear. The present study was undertaken to help in defining some potential mechanisms for this type of toxicity. Here, Cl.Ly1+2/-9 T-cells were exposed to varying levels of DBA and then several parameters, including cell survival, apoptosis, changes in mitochondrial potentials, and effects on select kinases (i.e., p38, ERK1/2, JNK1/2) were examined. The data showed that DBA significantly decreased Cl.Ly1+2/-9 cell viability in a dose-related manner. DBA also induced apoptosis, a decrease in mitochondrial trans-membrane potential, and up-regulated the protein expression of cleaved caspase-3. Moreover, DBA increased the phosphorylation of all three mitogen-activated protein kinases (MAPKs) evaluated. Pre-treatment with specific p38, ERK1/2, and JNK1/2 inhibitors (SB203580, U0126, SP600125, respectively) attenuated the inducible phosphorylation events. DBA also induced up-regulation of mRNA levels of the MAPKs downstream transcription factors ATF-2 and Elk-1. When taken together, the results suggest that DBA could induce murine Cl.Ly1+2/-9 T-cells apoptosis through mitochondria-dependent way, and activate the MAPKs pathways and downstream transcription factors ATF-2 and Elk-1.