Abstract Aims To compare the fecal levels of short‐chain fatty acids (SCFAs) in patients with mild cognitive impairment (MCI) and normal controls (NCs) and to examine whether fecal SCFAs could be used as the biomarker for the identification of patients with MCI. To examine the relationship between fecal SCFAs and amyloid‐β (Aβ) deposition in the brain. Methods A cohort of 32 MCI patients, 23 Parkinson's disease (PD) patients, and 27 NC were recruited in our study. Fecal levels of SCFAs were measured using chromatography and mass spectrometry. Disease duration, ApoE genotype, body mass index, constipation, and diabetes were evaluated. To assess cognitive impairment, we used the Mini‐Mental Status Examination (MMSE). To assess brain atrophy, the degree of medial temporal atrophy (MTA score, Grade 0–4) was measured by structural MRI. Aβ positron emission tomography with 18 F‐florbetapir (FBP) was performed in seven MCI patients at the time of stool sampling and in 28 MCI patients at an average of 12.3 ± 0.4 months from the time of stool sampling to detect and quantify Aβ deposition in the brain. Results Compared with NC, MCI patients had significantly lower fecal levels of acetic acid, butyric acid, and caproic acid. Among fecal SCFAs, acetic acid performed the best in discriminating MCI from NC, achieved an AUC of 0.752 ( p = 0.001, 95% CI: 0.628–0.876), specificity of 66.7%, and sensitivity of 75%. By combining fecal levels of acetic acid, butyric acid, and caproic acid, the diagnostic specificity was significantly improved, reaching 88.9%. To better verify the diagnostic performance of SCFAs, we randomly assigned 60% of participants into training dataset and 40% into testing dataset. Only acetic acid showed significantly difference between these two groups in the training dataset. Based on the fecal levels of acetic acid, we achieved the ROC curve. Next, the ROC curve was evaluated in the independent test data and 61.5% (8 in 13) of patients with MCI, and 72.7% (8 in 11) of NC could be identified correctly. Subgroup analysis showed that reduced fecal SCFAs in MCI group were negatively associated with Aβ deposition in cognition‐related brain regions. Conclusion Reductions in fecal SCFAs were observed in patients with MCI compared with NC. Reduced fecal SCFAs were negatively associated with Aβ deposition in cognition‐related brain regions in MCI group. Our findings suggest that gut metabolite SCFAs have the potential to serve as early diagnostic biomarkers for distinguishing patients with MCI from NC and could serve as potential targets for preventing AD.
In recent years, environmental pollution and resource waste have become the focus of heated discussion around the world. In order to realize green and sustainable development, the development of green supply chain (GSC) has attracted the attention of many scholars. The research object of this paper is the dual-channel green supply chain (DGSC) composed of online channels and offline channels. The supplier is the leader of the entire DGSC, and it needs to optimize the wholesale price of the product and the level of green investment to maximize its own benefit. In addition, the supplier also needs to establish contracts with network sales platform (NSP) and store sales platform (SSP) to increase the benefit of NSP and SSP, and ultimately increase the benefit level of the entire DGSC. Among them, we constructed a centralized decision (CD) model and a decentralized decision (DD) model, and obtained the optimal pricing, optimal greenness and optimal benefit of the supplier, NSP and SSP under the two models. We found that the benefits of SC members under the DD model are generally lower than those of the CC model. Therefore, we built contracts between the supplier, NSP and SSP to coordinate. Finally, we substituted specific parameters to verify the model. The following conclusions are drawn: (i) When consumers prefer online sales channels, it will positively affect the online sales price, online sales volume and greenness level of DGSC. At the same time, it negatively affects offline sales price and sales volume. (ii) The benefit of DGSC and the benefit of NSP, SSP, and the supplier show a phenomenon of decline first and then increase with respect to consumers’ preference for online sales channels. (iii) Under the coordination contract, the subsidy factor positively affects the benefits of the supplier and online and offline wholesale prices, and negatively affects the benefits of online platforms and physical stores.
Abstract The present study was undertaken to investigate the effect of iron dextran treatment on polyamine oxidase (PAO) activity, iron accumulation, and lipid peroxidation in livers and hearts of rats. PAO catalyzes oxidative deamination of polyamines, the cellular aliphatic cations. This reaction produces highly toxic hydrogen peroxide, 3-acetamidopropanal, and precursors of higher polyamines. The rats were given iron dextran daily for 7 d. In iron-dextran-treated rats, a marked increase in the hepatic level of iron was associated with enhanced lipid peroxidation and increased PAO activity. Though iron accumulation and lipid peroxidation in the iron-treated rats increased significantly in the heart, PAO activity remained unchanged. The paraffin sections of livers stained with Perls iron stain showed the presence of iron in macrophages and hepatocytes. The sections of hearts showed iron deposits only in macrophages, while myocytes showed no iron staining. These results show that although iron dextran treatment results in accumulation of iron in both liver and heart, it induces PAO activity only in liver. The significance of increased PAO activity in lipid peroxidation and fibrosis in iron-mediated injury is discussed. Additional informationNotes on contributorsUlka R. Tipnis Address correspondence to Ulka R. Tipnis, PhD, Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555-0609, USA.
Abstract Background: Amnesia in Alzheimer's disease (AD) could be due to disrupted encoding, consolidation dysfunction, or an impairment in the retrieval of stored memory information. The different memory phases relate with different parts of functional brain systems. Methods: We combine task functional magnetic resonance imaging and amyloid positron emission tomography in 72 participants (36 AD and 36 controls), to investigate the relationship between memory performance, memory phase-locked functional connectivity, and cortical β-amyloid deposition. Results: We found that AD was mainly characterized by decreased functional connectivity in a new data-driven Network composed of regions from default mode network, limbic network and frontoparietal network during the memory maintenance and retrieval phase. Within the Network, AD had more regions with reduced connectivity during the retrieval phase than other phases, locating mainly in the medial prefrontal cortex, posterior cingulate cortex, middle temporal and inferior parietal cortex of left hemisphere. Furthermore, functional connectivity in the Network related to memory performance. Crucially, the magnitude of the Network connectivity reduction during retrieval negatively correlated with mean cortical β-amyloid, and this relationship mediated the relationship between cortical β-amyloid and memory performance. Conclusions: Our findings show that memory deficiency in AD relates with decreased connectivity in specific network and cortical β-amyloid only during retrieval phase. These findings help to map impaired functional connectivity during memory phases and explain the relationship between memory deficiency and cortical β-amyloid.
Excitation-emission matrix fluorescence spectroscopy combined with fluorescence regional integration (FRI) analysis were adopted to analyze the water samples collected from the Lujiang River, which flows through the rapidly urbanizing areas of Beilun, Ningbo, in order to illuminate the composition and characteristics of the spatial distribution of fluorescent dissolved organic matter (FDOM), and further to explain its correlation with water quality in the urban river. The results showed that FDOM was composed of tyrosine-like, tryptophan-like, soluble microbial by-product-like, fulvic-like, and humic-like materials, and FDOM was dominated by protein-like components, accounting for 83.8% of the total fluorescence intensity, while humic-like components accounted for much less. The concentrations of the water quality parameters, such as total nitrogen, total phosphorus, and metals, were linearly correlated with the total fluorescence intensity of all components, indicating that FDOM was significantly related to the removal and transformation of nitrogen and phosphorus. The distribution of FDOM in different areas has the following characteristics:FDOM was low and not distinctly influenced by human activities in the upstream, while in the downstream, FDOM was high and showed the characteristics typical of that in urbanized rivers. Therefore, anthropogenic activities can greatly influence river water quality and the concentration and composition of FDOM.
Abstract Background Tai Chi has been shown to improve motor symptoms in Parkinson’s disease (PD), but its long-term effects was not clear and the related mechanism was not elucidated. Therefore, we investigated the mechanism of long-term Tai Chi training on improving motor symptoms in PD. Methods 95 early-stage PD patients were enrolled and randomly divided into Tai Chi (N = 32), brisk walking (N = 31) and no-exercise group (N = 32). All subjects were assessed at baseline, 6 months and 12 months after one-year intervention. Motor symptoms were evaluated by Berg balance scale (BBS), Unified PD rating scale (UPDRS), Timed Up and Go test (TUG) and 3D gait analysis. Functional MRI, plasma cytokine and metabolomics, blood Huntingtin interaction protein 2 ( HIP2 ) mRNA levels were analyzed to investigate the mechanisms of Tai Chi training at macro and molecular level. The longitudinal effects of self-changes were calculated using repeated measures ANOVA. Generalized estimating equations (GEE) was used to assess the association of longitudinal data of rating scales. Switch rates were used into the fMRI analysis. False discovery rate (FDR) correction was used to perform multiple correction. Results Tai Chi group had better performance in BBS, UPDRS, TUG and step width. Besides, Tai Chi had more advantages in improving BBS, step width than brisk walking. Improved BBS was correlated with enhanced visual network function and downregulation of IL-1β. Improvements in UPDRS were associated with enhanced default mode network function, decreased L-malic acid and 3-phosphoglyceric acid, increased adenosine and HIP2 mRNA levels. In addition, arginine biosynthesis, urea cycle, TCA cycle and beta oxidation of very long chain fatty acids were also improved by Tai Chi. Conclusions Long-term Tai Chi training improved motor function, especially gait and balance, in PD. Enhanced brain network function, reduced inflammation, improved amino acid metabolism, energy metabolism and neurotransmitters metabolism, decreased vulnerability to dopaminergic degeneration might be the mechanisms of Tai Chi effects. Trial registration: This study is registered at Chinese Clinical Trial Registry (Registration number: ChiCTR-OPC-16008074; Registration date: March 8, 2016).
Essential tremor (ET) is the most common movement disorder and share overlapping symptoms with Parkinson's disease (PD), making differential diagnosis challenging. Gut dysbiosis is regarded crucial in the pathogenesis of PD. Since ET patients also has comorbidity in gastrointestinal disorders, the relationship between gut microbiota and ET really worth investigating and may help distinguishing ET from PD. Fecal samples from 54 ET, 67 de novo PD and 54 normal controls (NC) were collected for 16S ribosomal RNA gene sequencing and quantitative real-time PCR. ET showed lower species richness (Chao1 index) than NC and PD. ET was with Bacteroides-dominant enterotype, while PD was with Ruminococcus-dominant enterotype. Compared with NC, 7 genera were significantly reduced in ET, 4 of which (Ruminococcus, Romboutsia, Mucispirillum, and Aeromonas) were identified to be distinctive with an area under the curve (AUC) of 0.705. Compared to PD, 26 genera were found significantly different from ET, 4 of which (Bacteroides, Fusobacterium, Phascolarctobacterium, and Lachnospira) were found distinguishable with an AUC of 0.756. Clinical association results indicated that Proteus was associated with disease severity (TETRAS) of ET, while Klebsiella was linked to depression and anxiety in ET. Functional predictions revealed that 4 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were altered in ET. This study reveals gut dysbiosis in ET and it provides new insight into the pathogenesis of ET and helps distinguishing ET from PD.
Schiff bases are a crucial component in various functional materials but often exhibit non-emissive behavior which significantly limits their potential applications as luminescent materials. However, traditional approaches to convert them into aggregate emitters often require intricate molecular design, tedious synthesis, and significant time and resource consumption. Herein, we present a cocrystallization-induced emission strategy that can transform non-emissive (hetero)aryl-substituted Schiff bases into green-yellow to yellow aggregate emitters via even simple grinding of a mixture of Schiff bases and 1,2,4,5-tetracyanobenzene (TCB) mixtures. The combined experimental and theoretical analysis revealed that the cocrystallization inhibits the C=N isomerization and promotes face-to-face π-π interaction, which restricts access to both the dark state and canonical intersection to ultimately induce emission. Furthermore, the induced emission enables the observation of solid-state molecular diffusion through fluorescence signals, advancing white light emission diodes, and notably, solution-processed organic light-emitting diodes based on cocrystal for the first time. This study not only highlights the potential of developing new C=N structural motifs for AIEgens but also could boost advancements in related structure motifs like C=C and N=N.
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