Rehmanniae Radix Preparata ameliorates behavioral deficits and hippocampal neurodevelopmental abnormalities in ADHD rat model.

Objectives: Abnormal hippocampal neurodevelopment, particularly in the dentate gyrus region, may be a key mechanism of attention-deficit/hyperactivity disorder (ADHD). In this study, we investigate the effect of the most commonly used Chinese herb for the treatment of ADHD, Rehmanniae Radix Preparata (RRP), on behavior and hippocampal neurodevelopment in spontaneously hypertensive rats (SHR). Methods: Behavior tests, including Morris water maze (MWM) test, open field test (OFT) and elevated plus maze (EPM) test were performed to assess the effect of RRP on hyperactive and impulsive behavior. Hippocampal neurodevelopment was characterized by transmission electron microscopy, immunofluorescence, Golgi staining and Nissl staining approaches. Regulatory proteins such as Trkb, CDK5, FGF2/FGFR1 were examined by Western blot analysis. Results: The results showed that RRP could effectively control the impulsive and spontaneous behavior and improve the spatial learning and memory ability. RRP significantly reduced neuronal loss and increased the number of hippocampal stem cells, and promoted synaptic plasticity. In addition, FGF/FGFR signaling was upregulated after RRP treatment. Conclusion: RRP can effectively reduce impulsive and spontaneous behavior and ameliorate hippocampal neurodevelopmental abnormalities in ADHD rat model.

Disrupted Balance of Gray Matter Volume and Directed Functional Connectivity in Mild Cognitive Impairment and Alzheimer's Disease.

BACKGROUND: Alterations in functional connectivity have been demonstrated in Alzheimer's disease (AD), an age-progressive neurodegenerative disorder that affects cognitive function; however, directional information flow has never been analyzed. OBJECTIVE: This study aimed to determine changes in resting-state directional functional connectivity measured using a novel approach, granger causality density (GCD), in patients with AD, and mild cognitive impairment (MCI) and explore novel neuroimaging biomarkers for cognitive decline detection. METHODS: In this study, structural MRI, resting-state functional magnetic resonance imaging, and neuropsychological data of 48 Alzheimer's Disease Neuroimaging Initiative participants were analyzed, comprising 16 patients with AD, 16 with MCI, and 16 normal controls. Volume-based morphometry (VBM) and GCD were used to calculate the voxel-based gray matter (GM) volumes and directed functional connectivity of the brain. We made full use of voxel-based between-group comparisons of VBM and GCD values to identify specific regions with significant alterations. In addition, Pearson's correlation analysis was conducted between directed functional connectivity and several clinical variables. Furthermore, receiver operating characteristic (ROC) analysis related to classification was performed in combination with VBM and GCD. RESULTS: In patients with cognitive decline, abnormal VBM and GCD (involving inflow and outflow of GCD) were noted in default mode network (DMN)-related areas and the cerebellum. GCD in the DMN midline core system, hippocampus, and cerebellum was closely correlated with the Mini- Mental State Examination and Functional Activities Questionnaire scores. In the ROC analysis combining VBM with GCD, the neuroimaging biomarker in the cerebellum was optimal for the early detection of MCI, whereas the precuneus was the best in predicting cognitive decline progression and AD diagnosis. CONCLUSION: Changes in GM volume and directed functional connectivity may reflect the mechanism of cognitive decline. This discovery could improve our understanding of the pathology of AD and MCI and provide available neuroimaging markers for the early detection, progression, and diagnosis of AD and MCI.

Altered Functional Connectivity of Basal Ganglia in Mild Cognitive Impairment and Alzheimer's Disease.

(1) Background: Alzheimer's disease (AD), an age-progressive neurodegenerative disease that affects cognitive function, causes changes in the functional connectivity of the default-mode network (DMN). However, the question of whether AD-related changes occur in the functional connectivity of the basal ganglia has rarely been specifically analyzed. This study aimed to measure the changes in basal ganglia functional connectivity among patients with AD and mild cognitive impairment (MCI) in their resting state using the functional connectivity density (FCD) value, the functional connectivity (FC) intensity, and the graph theory index, and to confirm their influence on clinical manifestations. (2) Methods: Resting-state functional MRI (rs-fMRI) and neuropsychological data from 48 participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) were used for analyses. The 48 ADNI participants comprised 16 patients with AD, 16 patients with MCI, and 16 normal controls (NCs). The functional connectivity of basal ganglia was evaluated by FCDs, FC strength, and graph theory index. We compared voxel-based FCD values between groups to show specific regions with significant variation and significant connectivity from ROI conduction to ROI analysis. Pearson's correlation analyses between functional connectivity and several simultaneous clinical variables were also conducted. Additionally, receiver operating characteristic (ROC) analyses associated with classification were conducted for both FCD values and graph theory indices. (3) Results: The level of FCD in patients with cognitive impairment showed obvious abnormalities (including short-range and long-range FCD). In addition to DMN-related regions, aberrant functional connectivity was also found to be present in the basal ganglia, especially in the caudate and amygdala. The FCD values of the basal ganglia (involving the caudate and amygdala) were closely related to scores from the Mini-Mental State Examination (MMSE) and the Functional Activities Questionnaire (FAQ); meanwhile, the graph theory indices (involving global efficiency and degree) of the basal ganglia (involving the caudate, amygdala, and putamen) were also found to be closely correlated with MMSE scores. In ROC analyses of both FCD and graph theory, the amygdala was of the utmost importance in the early-stage detection of MCI; additionally, the caudate nucleus was found to be crucial in the progression of cognitive decline and AD diagnosis. (4) Conclusions: It was systematically confirmed that there is a phenomenon of change in the functional connections in the basal ganglia during cognitive decline. The findings of this study could improve our understanding of AD and MCI pathology in the basal ganglia and make it possible to propose new targets for AD treatment in further studies.

Dynamic changes in rhizosphere fungi in different developmental stages of wheat in a confined and isolated environment.

As the core food crop of a bioregenerative life support system (BLSS), wheat is susceptible to pathogen infection due to the lack of effective microbial communities in the confined and isolated environment. Therefore, a thorough understanding of the dynamic changes in wheat rhizosphere fungi is of great significance for improving wheat production and ensuring the stability of the BLSS. In the current study, we collected samples of rhizosphere fungi in the four growth stages of wheat grown in the "Lunar Palace 365" experiment. We employed bioinformatics methods to analyze the samples' species composition characteristics, community network characteristics, and FUNGuild function analysis. We found that the species composition of rhizosphere fungi in the wheat at the tillering stage changed greatly in the closed and isolated environment, while the species composition in the seedling, flowering, and mature stage were relatively stable. The results of the FUNGuild function analysis showed that the functions of rhizosphere fungi changed during wheat development. The rhizosphere fungal community was centered on Ascomycota, Mortierellomycota, and Chytridiomycota, and the community showed the characteristics of a "small world" arrangement. The stage of wheat seedlings is characterized by a greater abundance, diversity, and complexity of the network of interactions in the rhizosphere mycorrhiza community, while the tillering stage exhibited a greater clustering coefficient. Based on the changes in species composition, guild function regulation, and community structure differences of the wheat rhizosphere fungi in the BLSS, our study identified the critical fungal species during wheat development, providing a reference for ensuring the health and yield of plants in the BLSS system. KEY POINTS: • The diversity, composition, FUNguild, and network structure of rhizosphere fungi were analyzed. • Ascomycota, Mortierellomycota, and Chytridiomycota were the center of the rhizosphere fungal community network. • The effects of different wheat developmental stages on the community composition, function, and network structure of rhizosphere fungi were examined.

'Green' nanotherapeutics from tea leaves for orally targeted prevention and alleviation of colon diseases.

Although synthesized nanotherapeutics (NTs) are attractive for the oral treatment of colon diseases, their clinical translations are constrained by the unsatisfactory therapeutic outcomes, potential adverse effects, and high cost of mass production. Here, we report the development of tea leaf-derived natural NTs with desirable particle sizes (140.0 nm) and negative surface charge (-14.6 mV). These natural exosome-like NTs were found to contain large amounts of lipids, some functional proteins, and many bioactive small molecules. Specifically, galactose groups on the surface of NTs could mediate their specific internalization by macrophages via galactose receptor-mediated endocytosis. Moreover, these NTs were able to reduce the production of reactive oxygen species, inhibit the expression of pro-inflammatory cytokines, and increase the amount of anti-inflammatory IL-10 secreted by macrophages. Orally administered NTs could efficiently inhibit the inflammatory bowel responses, restore disrupted colonic barriers and enhance the diversity and overall abundance of gut microbiota, thereby preventing or alleviating inflammatory bowel disease and colitis-associated colon cancer. The present study brings new insights to the facile application of a versatile and robust natural nanoplatform for the prevention and treatment of colon diseases.

The gut microbiota and its metabolites in mice are affected by high heat treatment of Bactrian camel milk.

Heat treatment is the most common method used to make milk safe; however, it leads to changes in the organoleptic and nutritional properties of milk. This study aimed to investigate the effects of different heat treatments on nutrients and microbiota of camel milk. The results showed that the nutrient composition of camel milk could be influenced by heat treatment. Ultra-high-temperature treatment of samples significantly reduced levels of camel milk proteins, vitamin C, and lactose, but did not significantly alter the amino acids content. Analysis of 16S rRNA amplicon sequences demonstrated that the composition of the intestinal microbiota of mice fed different heat-treated camel milks changed, as did the production of short-chain fatty acids as determined by gas chromatography-mass spectrometry. High temperature/short time treatment had similar effects to UHT treatment on microbial diversity of camel milk; however, the low temperature/long time treatment had different effects. In addition, higher-temperature treatments changed the abundance of key bacteria at the genus level. These results demonstrated that different heat treatments not only resulted in some nutrient loss, but also changed the proliferation of some probiotic genera. Our results could provide the basis for the potential industrial application of camel milk processing technologies.

The effect of diabetes on perioperative complications following spinal surgery: a meta-analysis.

BACKGROUND: Degenerative spinal diseases and diabetes mellitus (DM) have increasingly become a social and economic burden. The effect of DM on spinal surgery complications reported by previous studies remains controversial. METHODS: We searched MEDLINE, Cochrane CENTRAL, ScienceDirect, EMBASE, and Google Scholar to identify studies reporting the relationship between DM and spinal surgery complications. Two independent reviewers performed independent data abstraction. The I2 statistic was used to assess heterogeneity. A fixed-effects or random-effects model was used for the meta-analysis. RESULTS: Twenty-four studies met the inclusion criteria. Surgical site infection and the incidence of deep venous thrombosis after spinal surgery were significantly higher in patients with than in patients without diabetes, and the length of hospital stay was significantly longer in patients with diabetes (P<0.05). No significant differences were observed in the risk of reoperation, blood loss, and operation time between patients with and those without diabetes (P.0.05). CONCLUSION: Patients with diabetes have a higher risk when undergoing spinal surgery than patients without diabetes. Diabetes increases the risks of postoperative mortality, surgical site infection, deep venous thrombosis, and a prolonged hospitalization time after spinal surgery.

The efficacy and safety of topical administration of tranexamic acid in spine surgery: a meta-analysis.

BACKGROUND: We conducted a meta-analysis from randomized controlled trials (RCTs) and non-RCTs to assess the efficacy and safety of tranexamic acid (TXA) in spine surgery. METHODS: Potentially relevant academic articles were identified from the Cochrane Library, MEDLINE (1966-2017.11), PubMed (1966-2017.11), Embase (1980-2017.11), and ScienceDirect (1985-2017.11). Secondary sources were identified from the references of the included literature. The pooled data were analyzed using RevMan 5.1. RESULTS: Three RCTs and one non-RCT met the inclusion criteria. There were significant differences in total blood loss (MD = - 267.53, 95% CI - 373.04 to - 106.02, P < 0.00001), drainage volume (MD = - 157.00, 95% CI - 191.17 to - 122.84, P < 0.00001), postoperative hemoglobin level (MD = 0.95, 95% CI 0.44 to 1.47, P = 0.0003), and length of hospital stay (MD = - 1.42, 95% CI - 1.92 to - 0.93, P < 0.00001). No significant differences were found regarding transfusion requirement, deep vein thrombosis (DVT), pulmonary embolism (PE), wound hematoma, and infection between the two groups. CONCLUSIONS: The present meta-analysis indicated that the topical application of TXA in spinal surgery decreases the total blood loss and drainage volume and preserves higher postoperative hemoglobin level without increasing the risk of DVT infection, hematoma, DVT, and PE.